2024-03-29T15:01:52Zhttp://diposit.ub.edu/dspace-oai/requestoai:diposit.ub.edu:2445/1070362024-03-12T17:02:13Zcom_2445_34657col_2445_106688
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Latella, Ivan
author
2016-06-27
[eng] Two main topics are examined in this thesis: classical systems with long-range interactions and thermal radiation in the near-field regime. In the first part, we present a thermodynamic approach describing systems with long-range interactions which takes into account the intrinsic nonadditivity in these systems. The basic concept behind this approach is to consider a large ensemble of replicas of the system where the standard formulation of thermodynamics can be naturally applied and the properties of a single system can be consequently inferred. The formulation of the thermodynamic for these systems is in close connection with Hill's thermodynamics of systems with small number of particles. It is shown that systems with long-range interactions can attain equilibrium configurations in the unconstrained ensemble. In this statistical ensemble, the control parameters are the temperature, pressure, and chemical potential, while the energy, volume, and number of particles fluctuate. We consider a solvable model as a concrete example of a system that achieves stable equilibria in this ensemble. We also give a complete description of the phase-diagram of the Thirring model in both the microcanonical and the canonical ensemble, highlighting the main features of ensemble inequivalence. I the second part, we study energy and entropy fluxes of near-field thermal radiation in many-body systems, with application to energy-conversion processes. It is shown that the maximum work that can be obtained from the thermal radiation emitted by two planar sources in the near-field regime is much larger than that corresponding to the blackbody limit. This quantity as well as an upper bound for the efficiency of the process are computed from the formulation of thermodynamics in the near-field regime. The case when the difference of temperatures of the hot source and the environment is small, relevant for energy harvesting, is studied in detail. We also show that thermal radiation energy conversion can be more efficient in the near-field regime. Moreover, by analyzing the thermodynamic performance of three-body near-field heat engines, we demonstrate that the power they supply can be substantially larger than that of two-body systems, showing their strong potential for energy harvesting. Theoretical limits for energy and entropy fluxes in three-body systems are discussed and compared with their corresponding two-body counterparts. Such considerations confirm that the thermodynamic availability in energy-conversion processes driven by three-body photon tunneling can exceed the thermodynamic availability in two-body systems.
[spa] En esta tesis se estudia la termodinámica y mecánica estadística de sistemas clásicos con interacciones de largo alcance y de la radiación térmica de campo cercano. En la primera parte, introducimos un formalismo termodinámico apropiado para sistemas con interacciones de largo alcance, en el cual se tiene en cuenta la no aditividad intrínseca en estos sistemas. Para estos sistemas, mostramos que la temperatura, presión y potencial químico pueden ser variables independientes. A su vez, dependiendo del sistema, lo anterior da lugar a poder tomar estas variables como parámetros de control para definir las configuraciones de equilibrio. Para estudiar este hecho, hemos introducido un modelo que cumple estas condiciones. En la segunda parte de la tesis, hemos desarrollado un esquema termodinámico para describir procesos de conversión de energía en trabajo útil en sistemas con interacción térmica radiativa en el campo cercano. Se ha mostrado explícitamente que de la radiación térmica de campo cercano puede extraerse un trabajo útil mayor que el obtenido de la radiación térmica de cuerpo negro. Hemos mostrado, además, que la potencia obtenida en sistemas con tres cuerpos en interacción puede ser considerablemente superior que en el caso de dos cuerpos.
http://hdl.handle.net/2445/107036
http://hdl.handle.net/10803/400405
Statistical thermodynamics of long-range interacting systems and near-field thermal radiation
oai:diposit.ub.edu:2445/1071662024-03-12T17:02:13Zcom_2445_34657col_2445_106688
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Suñé Simon, Marc
author
2016-11-25
[eng] Brownian motion refers to the random movement that undergo mesosized particles suspended in a simple sol- vent. Einstein’s probabilistic approach to the Brownian motion is founded on the principal that it is on account of the molecular motions of heat; it can be summarized in three postulates: particles do not to interact with each other, the motion is memoryless at long times, and the distribution of displacements possesses at least two lower moments. According to the Einstein’s theory, the displacements of Brownian particles ought to exhibit a Gaussian distribution whose variance is proportional to time through the diffusion coefficient, that involves the temperature and the friction coefficient. May a constant external force be applied, the mean displacement scales linearly with time. This scenario is referred to as normal transport and diffusion. The thesis aims at exploring the deviations of normal transport and diffusion to exhibit Brownian particles in a disordered medium. The method of choice are numerical simulations of the classical Langevin equation, a generalization of Newtonian equations so as to account for the Brownian trajectories. To grasp the influence of the disorder’s attributes on Brownian motion is the main focus of the thesis. Further, the outcome sheds light into the physical foundations of the anomalous transport and diffusion. Complementarily, some refinements are made on the algorithms employed to simulate the stochastic differential equations. First, it is reviewed the Brownian motion in a periodic potential. According to the attained outcome, some hypothesis are conjectured for the subsequent explorations in disordered media: transport anomalies—if any— would be only of subtransport type when the disorder is static, enhanced diffusion and superdiffusion are likely to be reached, and anomalous transport and diffusion regimes might be transient in dynamic landscapes. For overdamped Brownian particles in a disordered static potential, the anomalous regimes are characterized by the time exponents that exhibit the statistical moments of the ensemble of particle trajectories, as well as by the particle displacement distributions and the clouds of particles. This case of study bears out that the length scale of the roughness of the potential is an essential parameter in the understanding of the effect of disorder. Besides, the shape of the particle density histograms and the particle clouds have been proved to be related to the anomalies. The analogous scenario in the underdamped limit leads to the instantaneous velocity distributions, that disclose appealing properties of the system. This case of study proves that the anomalous transport and diffusion regimes occur no matter the damping, yet they come about at higher forces for high friction conditions. Overdamped Brownian motion of particles in random landscapes of moving deformable obstacles is also studied. It is settled an effective set of quantities to portray the transport and diffusion properties. The characteristic time scale constrains the time span of anomalies, and thus the subsequent steady transport and diffusion coefficients. For a given density of obstacles, both trafficking and diffusion are favored by wider and therefore fewer obstacles. To end, a high density of obstacles hinders both transport and dispersion. Algorithms to carry out the numerical simulations are discussed. A novel method to build Gaussian potential landscapes with arbitrary spatial correlation functions and the only requirement of isotropy is developed. It has the particularity that, although it uses the Fourier space, its constraints are in real space. A refreshing architec- ture for simulating random dynamic obstacles is also covered. Finally, two supplementary physical systems are addressed; the physics of particles undergoing changing viscosi- ties and confinement to quasi 2 d layers, and the transport of the motor KIF1A in a two–dimensional ratchet model that mimics a microtubule.
[cat] El moviment Brownià és el bellugueig aleatori que efectuen les partícules de tamany micromètric quan estan suspeses en un dissolvent. Segons la formulació d’Einstein, els desplaçaments que efectuen les partícules exhibeixen una distribució Gaussiana de mitjana nul·la i variança proporcional al temps. La constant que relaciona la dispersió del conjunt de desplaçaments i el temps és el coeficient de difusió, que depèn de la temperatura i el coeficient de fricció. Si les partícules estan sotmeses a una força externa, la velocitat mitjana del conjunt és no nul·la, donant lloc al fenòmen del transport. En aquestes condicions, el valor mig de la distribució de desplaçaments presenta un creixement lineal amb el temps. Tanmateix, el seguiment de partícules sotmeses al moviment Brownià en ambients complexos dóna lloc a desviacions—anomalies—en els resultats clàssics del transport i la difusió, és a dir, dependències no lineals de la mitjana i la dispersió respecte el temps. Els ambients en els quals s’observen aquestes anomalies es poden caracteritzar per mitjà de potencials no–lineals que presenten barreres que modifiquen la distribució dels desplaçaments. L’objecte de la tesi és explorar aquestes anomalies del transport i la difusió de partícules Brownianes sotmeses a un potencial desordenat. El mètode emprat és la simulació numèrica de les equacions de Langevin clàssiques, una adaptació de la mecànica de Newton que permet obtenir les trajectòries de les partícules. En concret, la tesi indaga en les causes que motiven l’aparició de les anomalies i la influència que hi tenen les propietats del potencial desordenat, la força externa, la temperatura, el coeficient de fregament—únicament en l’aproximació d’infraesmorteïment—, etc. En paral·lel, s'han desenvolupat noves tècniques numèriques per simular les equacions dinàmiques estocàstiques. La tesi inclou diversos casos d'estudi en funció de les característiques del potencial no–lineal—periòdic, desordenat estàtic, desordenat dinàmic—i de la dissipació de l'energia—règims sobreesmorteït i infraesmorteït—. Així mateix, també es presenten dos treballs d'aplicació del moviment Brownià per modelitzar casos experi- mentals; l'atrapament de partícules en una interfície quasi–plana amb una viscositat canviant, i el transport del motor KIF1A a través d'un microtúbol.
http://hdl.handle.net/2445/107166
http://hdl.handle.net/10803/400564
Anomalous transport and diffusion of Brownian particles on disordered landscapes
oai:diposit.ub.edu:2445/1072142024-03-12T17:02:13Zcom_2445_34657col_2445_106688
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Luna Escalante, Juan Camilo
author
2016-10-14
[eng] Intercellular signalling is a mechanism by which cells communicate and mediate coordinated responses. In this Thesis we perform theoretical and computational analyses to evaluate spatio-temporal organizations that can arise in developing embryos through juxtacrine signalling mediated by Notch receptor. Juxtacrine signalling is a type of intercellular communication in which adjacent cells mutually interact through membrane-attached proteins (receptors and ligands). In the case of Notch signalling, the ligands are regulated by the signalling, establishing a feedback loop on the activation of the signal between adjacent cells. Our study focused on the following open questions: 1. What coordinated responses arise when Notch signalling is activated by two (or more) co-expressing ligands? 2. What is the effect on the response mediated by Notch signalling when considering a gene involved in cell differentiation that promotes it on transcription, but in turn is repressed by the signal? 3. Which processes can modulate the signalling efficiency of a ligand? These questions encompass aspects occurring at different levels, ranging from the type of response that arises in a tissue (salt-and-pepper patterning, homogeneous states or propagation of a cell fate in an expansive wave), the signalling state of cells (sending, receiver, among others), up to the dynamics of the intracellular processing of Notch. We used a modelling and computational approach for their study and compared, when possible, with previously reported phenotypes in developing embryos.
[spa] La vía de señalización de Notch es un mecanismo de comunicación inter-celular yuxtacrina. La señal de Notch se activa tras la unión del ligando en una célula con el receptor en otro célula adyacente. La vía de Notch está ampliamente asociada a respuestas de coordinación espacio-temporal que ocurren durante el desarrollo de Metazoos, como es la formación de los patrones salt-and-pepper. Cómo Notch puede mediar este tipo de respuestas es una pregunta de gran interés tanto en física de sistemas alejados del equilibrio como en biología del desarrollo. Numerosos trabajos experimentales y teóricos han servido para entender el funcionamiento de la vía de Notch y su papel en la formación de respuestas complejas. Sin embargo, quedan ciertas preguntas sin responder aún. En esta Tesis abordamos algunas de estas cuestiones, utilizando una aproximación teórica y computacional y comparando nuestros resultados cuando es posible con fenotipos publicados con anterioridad. Las preguntas abordadas son: 1. Es bien sabido que la señal de Notch puede ser activada por distintos tipos de ligando, los cuales pueden expresarse simultáneamente durante el desarrollo. Por tanto nos preguntamos, ¿Qué respuestas de coordinación espacio-temporal surgen cuando la señal de Notch es activada por varios tipos de ligando? Nuestros resultados evalúan la relevancia de compartir y competir por recursos para la señalización y de diferencias de la eficiencia de señalización entre ligandos en la aparcición de organizaciones espacio- temporales (patrones periódicos de dos tipos celulares, por ejemplo) y en los estados de señalización de las células. 2. Es conocido que la inhibición lateral mutua entre células adyacentes mediada por Notch es un mecanismo suficiente para generar patrones periódicos de dos tipos celulares. Además, la vía de Notch implica numerosos pasos, entre ellos, retroalimentaciones positivas dentro de la propia célula de los genes que regulan la diferenciación. ¿Qué efecto tiene esta retroalimentación en la respuesta mediada por Notch? Nuestros resultados muestran que dicha auto-activación hace robusta la diferenciación celular. 3. Diferentes ligandos pueden activar distintos niveles de la señal de Notch. Estas diferencias pueden estar mediadas por modificaciones post-transduccionales del receptor Notch. Nos preguntamos ¿Qué procesos durante la formación de la señal pueden modular la eficiencia de señalización de los ligandos? Nuestros resultados muestran cómo la eficiencia de señalización de un ligando depende de la dinámica de procesamiento y degradación del complejo receptor-ligando.
http://hdl.handle.net/2445/107214
http://hdl.handle.net/10803/400610
Spatio-temporal dynamics of intercellular Notch signaling: a modeling approach
oai:diposit.ub.edu:2445/1116052024-03-12T17:02:13Zcom_2445_34657col_2445_106688
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Stern Taulats, Enric
author
2017-04-07
[eng] Solid state materials are candidates to exhibit a large field-driven thermal response in the vicinity of first-order transitions. The strong sensitivity of the transition temperature with the applied field and the latent heat associated with the change of phase can give rise to the giant magneto-, electro-, baro-, and elastocaloric effects. Furthermore, the coupling between structural, magnetic and electronic degrees of freedom at the transition regime enables the thermal response to be driven by multiple fields and, thus, giving rise to the multicaloric effect. In the last years, the interest in understanding and tailoring novel caloric materials has exceptionally grown in view of their potential application to alternative cooling technologies for large scale industry. The present thesis reports the giant caloric effects encompassing the Fe49Rh51 magnetovolumic transition, the magnetostructural martensitic transformation in Ni-Mn based Heusler alloys, and the ferroelectric perovskites BaTiO3 and Pb(Sc0.5Ta0.5)O3. The physical conditions for the optimization of the thermal response which yield to an enlarged magnitude and operation range are explored, as well as the corresponding reproducibility upon field cycling and the potential multicaloric character. This evaluation is achieved by means of a complete caloric characterization in which the calorimetric experimental techniques which have been developed in purpose are crucial.
[cat] Els materials d'estat sòlid són susceptibles de mostrar una gran resposta tèrmica induïda per un camp extern a l'entorn de transicions de fase de primer ordre. La forta sensitivitat de la temperatura de transició amb el camp aplicat i la calor latent associada amb el canvi de fase poden donar lloc als efectes magneto-, electro-, baro- i elastocalòric gegants. A més, l'acoblament entre els graus de llibertat estructurals, magnètics i electrònics en el règim de transició possibilita que la resposta tèrmica sigui induïda per múltiples camps, originant així l'efecte multicalòric. En els darrers anys, l'interès en entendre i elaborar materials calòrics ha crescut excepcionalment, amb l'ull posat en les aplicacions potencials en tecnologies de refrigeració alternatives per a la indústria a gran escala. La present tesi reporta els efectes calòrics gegants que acompanyen la transició magnetovolúmica del Fe49Rh51, la transformació martensítica en aliatges Heusler amb base de Ni-Mn, i les perovskites ferroelèctriques de BaTiO3 i de Pb(Sc0.5Ta0.5)O3. S'exploren les condicions físiques propícies per a una optimització de la resposta tèrmica que resulten amb un eixamplament en magnitud i en rang d'operació, així com també la reproducibilitat corresponent sota ciclatge i el potencial caràcter multicalòric. Aquesta avaluació s'aconsegueix per mitjà d'una caracterització calòrica completa en què les tècniques experimentals calorimètriques que s'han desenvolupat amb aquest propòsit són crucials.
http://hdl.handle.net/2445/111605
http://hdl.handle.net/10803/403464
Giant caloric effects in the vicinity of first-order phase transitions
oai:diposit.ub.edu:2445/1134082024-03-12T17:02:13Zcom_2445_34657col_2445_106688
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Arauz-Garofalo, Gianluca
author
2017-06-13
[eng] Throughout this thesis we have assessed the prospects of microwave spectrometry (MWS) as a non-ionizing non-invasive monitoring alternative for stented patients in a very early proof-of-concept stage. In Chapter 1 we have provided a generalist retrospective medical background along with a state-of-the-art summary of existing microwave-based stent monitoring approaches. First, we have introduced cardiovascular diseases in general, and ischemic heart disease in particular. Next we have reviewed how percutaneous coronary interventions addressed the medical problem represented by atherosclerosis, giving a special emphasis to balloon angioplasty, bare-metal stenting and drug-eluting stenting. We have further exposed how the outcomes of such revolutionary strategies were compromised by the high rates of post-procedural complications, making unavoidable the invasive and ionizing follow-up of stented patients. Finally, we have summarized existing non-invasive and non-ionizing stent monitoring alternatives based in microwave techniques. In Chapter 2 we have introduced the working principle of our MWS setup. We have first presented how this arrangement can obtain the absorbance of a stent as a function of the frequency and the incidence angle of the microwave fields. We have also shown how these data are combined in a single two-dimensional chart, and how we recognize therein the characteristic resonance frequencies of stents at a glance. As an example, we have presented a typical absorbance diagram to illustrate the general features of such resonances. In particular we have highlighted that these resonances are discrete and have multi-lobed angular patterns. In Chapter 3 we have characterized many stents having a wide variety of nominal sizes to better understand their characteristic resonances in terms of microwave scattering. First, we have found that the resonance frequency obeys a reciprocal dependence on the stent length. This has allowed us to obtain an empirical expression for such relationship just by adjusting two fitting parameters. However, we have not been able to find an analogous expression for the dependence on the stent diameter. In any case, while investigating the latter, we have unexpectedly uncovered how the particular stent architecture influences the corresponding resonance frequencies. By gathering all these individual results we have finally suggested a straightforward half-theoretical half-empirical model linking the resonance frequencies of stents with their structural integrity (through their length), with their particular architecture (through the scaling factor), as well as with their surrounding medium (through the dielectric permittivity and the magnetic permeability). We have also theoretically estimated the resonance frequencies of implanted stents from their corresponding values in free space conditions, showing that in vivo resonance frequencies should be around one order of magnitude smaller than their free space counterparts. Finally, in Chapters 4 and 5 we have explored the potential diagnostic capabilities of MWS in two possible scenarios: stent fracture (SF) and in-stent neoatherosclerosis (ISNA). We have started both chapters reviewing the incidence, the medical implications, and the mechanism of these two stent-related complications. SF has been evaluated in Chapter 4 by means of two “fracture tests” consisting in a successive series of strut cuts. We have shown that MWS provides qualitative indicators for single and multiple strut fractures (downshift of the fundamental resonance frequency), and also quantitative indicators for single or multiple complete transverse linear SFs (split and upshift of that frequency). ISNA has been evaluated in Chapter 6 by means of four ``cholesterol tests'' consisting in a gradual process of increasing cholesterol deposition. We have shown that MWS provides an indicator for a growing presence of cholesterol around a stent (downshift of the fundamental resonance frequency). We have concluded this chapter calculating the theoretical evolution of the resonance frequencies along a cholesterol deposition process, estimating the upper limit for the resonance frequency displacement. Taking together the results we have reported in Chapters 5 and 6, we have shown that MWS could potentially warn about SF and ISNA.
http://hdl.handle.net/2445/113408
http://hdl.handle.net/10803/404376
Prospects of microwave spectrometry for vascular stent monitoring. Towards a non-invasive and non-ionizing follow-up alternative
oai:diposit.ub.edu:2445/1191502024-03-12T17:02:13Zcom_2445_34657col_2445_106688
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Tibau Martorell, Elisenda
author
2017-09-15
[eng] In the present thesis, we propose to explore neuronal circuits at the mesoscale, an approach in which one monitors small populations of few thousand neurons and concentrates in the emergence of collective behavior. In our case, we carried out such an exploration both experimentally and numerically, and by adopting an analysis perspective centered on time series analysis and dynamical systems. Experimentally, we used neuronal cultures and prepared more than 200 of them, which were monitored using fluorescence calcium imaging. By adjusting the experimental conditions, we could set two basic arrangements of neurons, namely homogeneous and aggregated. In the experiments, we carried out two major explorations, namely development and disintegration. In the former we investigated changes in network behavior as it matured; in the latter we applied a drug that reduced neuronal interconnectivity. All the subsequent analyses and modeling along the thesis are based on these experimental data. Numerically, the thesis comprised two aspects. The first one was oriented towards a simulation of neuronal connectivity and dynamics. The second one was oriented towards the development of linear and nonlinear analysis tools to unravel dynamic and connectivity aspects of the measured experimental networks. For the first aspect, we developed a sophisticated software package to simulate single neuronal dynamics using a quadratic integrate–and–fire model with adaptation and depression. This model was plug into a synthetic graph in which the nodes of the network are neurons, and the edges connections. The graph was created using spatial embedding and realistic biology. We carried out hundreds of simulations in which we tuned the density of neurons, their spatial arrangement and the characteristics of the fluorescence signal. As a key result, we observed that homogeneous networks required a substantial number of neurons to fire and exhibit collective dynamics, and that the presence of aggregation significantly reduced the number of required neurons. For the second aspect, data analysis, we analyzed experiments and simulations to tackle three major aspects: network dynamics reconstruction using linear descriptions, dynamics reconstruction using nonlinear descriptors, and the assessment of neuronal connectivity from solely activity data. For the linear study, we analyzed all experiments using the power spectrum density (PSD), and observed that it was sufficiently good to describe the development of the network or its disintegration. PSD also allowed us to distinguish between healthy and unhealthy networks, and revealed dynamical heterogeneities across the network. For the nonlinear study, we used techniques in the context of recurrence plots. We first characterized the embedding dimension m and the time delay δ for each experiment, built the respective recurrence plots, and extracted key information of the dynamics of the system through different descriptors. Experimental results were contrasted with numerical simulations. After analyzing about 400 time series, we concluded that the degree of dynamical complexity in neuronal cultures changes both during development and disintegration. We also observed that the healthier the culture, the higher its dynamic complexity. Finally, for the reconstruction study, we first used numerical simulations to determine the best measure of ‘statistical interdependence’ among any two neurons, and took Generalized Transfer Entropy. We then analyzed the experimental data. We concluded that young cultures have a weak connectivity that increases along maturation. Aggregation increases average connectivity, and more interesting, also the assortativity, i.e. the tendency of highly connected nodes to connect with other highly connected node. In turn, this assortativity may delineates important aspects of the dynamics of the network. Overall, the results show that spatial arrangement and neuronal dynamics are able to shape a very rich repertoire of dynamical states of varying complexity.
[cat] L’habilitat dels teixits neuronals de processar i transmetre informació de forma eficient depèn de les propietats dinàmiques intrínseques de les neurones i de la connectivitat entre elles. La present tesi proposa explorar diferents tècniques experimentals i de simulació per analitzar la dinàmica i connectivitat de xarxes neuronals corticals de rata embrionària. Experimentalment, la gravació de l’activitat espontània d’una població de neurones en cultiu, mitjançant una càmera ràpida i tècniques de fluorescència, possibilita el seguiment de forma controlada de l’activitat individual de cada neurona, així com la modificació de la seva connectivitat. En conjunt, aquestes eines permeten estudiar el comportament col.lectiu emergent de la població neuronal. Amb l’objectiu de simular els patrons observats en el laboratori, hem implementat un model mètric aleatori de creixement neuronal per simular la xarxa física de connexions entre neurones, i un model quadràtic d’integració i dispar amb adaptació i depressió per modelar l’ampli espectre de dinàmiques neuronals amb un cost computacional reduït. Hem caracteritzat la dinàmica global i individual de les neurones i l’hem correlacionat amb la seva estructura subjacent mitjançant tècniques lineals i no–lineals de series temporals. L’anàlisi espectral ens ha possibilitat la descripció del desenvolupament i els canvis en connectivitat en els cultius, així com la diferenciació entre cultius sans dels patològics. La reconstrucció de la dinàmica subjacent mitjançant mètodes d’incrustació i l’ús de gràfics de recurrència ens ha permès detectar diferents transicions dinàmiques amb el corresponent guany o pèrdua de la complexitat i riquesa dinàmica del cultiu durant els diferents estudis experimentals. Finalment, a fi de reconstruir la connectivitat interna hem testejat, mitjançant simulacions, diferents quantificadors per mesurar la dependència estadística entre neurona i neurona, seleccionant finalment el mètode de transferència d’entropia gereralitzada. Seguidament, hem procedit a caracteritzar les xarxes amb diferents paràmetres. Malgrat presentar certs tres de xarxes tipus ‘petit món’, els nostres cultius mostren una distribució de grau ‘exponencial’ o ‘esbiaixada’ per, respectivament, cultius joves i madurs. Addicionalment, hem observat que les xarxes homogènies presenten la propietat de disassortativitat, mentre que xarxes amb un creixent nivell d’agregació espaial presenten assortativitat. Aquesta propietat impacta fortament en la transmissió, resistència i sincronització de la xarxa.
http://hdl.handle.net/2445/119150
http://hdl.handle.net/10803/460683
Linear and nonlinear approaches to unravel dynamics and connectivity in neuronal cultures
oai:diposit.ub.edu:2445/1195792024-03-12T17:02:13Zcom_2445_34657col_2445_106688
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Alert Zenón, Ricard
author
2018-01-12
[eng] In this thesis, we have studied mechanical aspects of some biological processes in cells and tissues, which we addressed by developing theoretical models based on the physics of soft active matter. The thesis contains three parts that focus on different biological systems.
In Part I, we study the adhesion between the plasma membrane and the actin cortex of eukaryotic cells. We propose a continuum model for membrane-cortex adhesion that couples the mechanics and hydrodynamics of the membrane to the force-dependent binding kinetics of the linker proteins. We predict the critical pressure difference that causes membrane-cortex detachment, and we discuss how cortical tension can be inferred from micropipette suction experiments. Then, we study the fluctuations of an adhered membrane, and suggest ways in which our predictions could allow probing membrane-cortex adhesion in fluctuation spectroscopy experiments.
Then, we employ the proposed model to study the nucleation of blebs, which are balloon-like membrane protrusions arising from a local membrane-cortex detachment. We show that bleb nucleation is governed by membrane peeling, the fracture propagation process whereby adjacent membrane-cortex bonds break sequentially. Through this mechanism, bleb nucleation is not determined by the energy of a local detachment like in the classical nucleation picture, but rather by the kinetics of membrane-cortex linkers. We predict the critical radius for bleb nucleation through membrane peeling and the corresponding effective energy barrier. Finally, we simulate a fluctuating adhered membrane to obtain the probability distribution of bleb nucleation times.
In Part II, we study the dynamics of active polar gels, which are soft materials, usually transiently-crosslinked polymeric networks, that are maintained out of equilibrium by internal processes that continuously transduce energy. We derive the constitutive equations of an active polar gel from a mesoscopic model for the dynamics of the molecules that crosslink the polar elements of the system. This way, we establish a connection between the molecular properties and the macroscopic behaviour of active polar gels. Specifically, we explicitly obtain the transport coefficients in terms of molecular parameters, showing that all transport coefficients have an active contribution that stems from breaking detailed balance for the crosslinker binding kinetics.
In Part III, we study cell colonies and tissues, focusing in collective cell migration and tissue morphology. First, we propose a particle-based description of cell colonies to study how the different organizations of cells in tissues emerge from intercellular interactions. The model intends to capture generic cellular behaviours such as cell migration, adhesion, and cell-cell overlapping. In addition, it models the so-called contact inhibition of locomotion (CIL), which repolarizes cell migration away from cell-cell contacts, as a torque on the migration direction. We show how CIL yields an effective repulsion between cells, which allows to predict transitions between non-cohesive, cohesive, and 3D tissues. We conclude that, at low cell-cell adhesion, CIL hinders the formation of cohesive tissues. Yet, in continuous cell monolayers, CIL gives rise to self-organized collective motion, ensures tensile stresses in the monolayer, and opposes cell extrusion, thereby hindering the collapse of the monolayer into a 3D aggregate.
Then, we focus on the spreading of epithelial monolayers, which we address by means of a continuum model based on the theory of active polar gels. First, we concentrate on the wetting transition of epithelial tissues, which separates monolayer spreading from retraction towards a 3D aggregate — namely the equivalent of a fluid droplet. We show that a critical radius exists for the wetting transition, which does not exist in the classical wetting picture. Thus, we show how the wetting properties of tissues emerge from active cellular forces, evidencing that the wetting transition has an active nature.
Finally, we study the morphological stability of the front of a spreading monolayer. The model predicts that traction forces cause a long-wavelength instability of the monolayer front, whereas tissue contractility has a stabilizing effect. The predicted instability can explain the formation of finger-like multicellular protrusions observed during epithelial spreading. It can also explain the symmetry breaking of tissue shape observed during monolayer dewetting. By fitting the predictions to experimental data, we infer the monolayer viscosity and the noise intensity of tissue shape fluctuations, which we suggest to have an active origin.
[cat] En aquesta tesi hem estudiat aspectes mecànics d'alguns processos biològics en cèl·lules i teixits, que hem abordat desenvolupant models teòrics basats en la física de la matèria tova activa. La tesi té tres parts centrades en sistemes biològics diferents.
En la primera part s'estudia l'adhesió entre la membrana plasmàtica i el còrtex d'actina de les cèl·lules eucariotes. Proposem un model continu per l'adhesió membrana-còrtex que acobla la mecànica i la hidrodinàmica de la membrana amb la cinètica de les proteïnes que ancoren la membrana al còrtex. Prediem la pressió crítica pel desenganxament i estudiem les fluctuacions de la membrana adherida. Després, ens centrem en la nucleació de butllofes cel·lulars, que són protrusions degudes a desenganxaments locals de la membrana. Mostrem que la nucleació de butllofes cel·lulars està governada pel procés de pelat de la membrana, pel qual proteïnes connectores adjacents es desenganxen seqüencialment. Per aquest mecanisme, la nucleació de butllofes no està determinada per l'energia com en l'escenari clàssic sinó per la cinètica dels connectors.
A la segona part es deriven les equacions constitutives d'un gel polar actiu a partir d'un model mesoscòpic per la dinàmica de les molècules entrellaçadores. Així, prediem explícitament els coeficients de transport dels gels polars actius en termes de paràmetres moleculars. Tots els coeficients de transport tenen una contribució activa, provinent del trencament de balanç detallat per la cinètica dels entrellaçadors.
A la tercera part estudiem colònies cel·lulars i teixits. Primer, proposem un model de partícules per estudiar com les diferents organitzacions dels teixits emergeixen de les interaccions intercel·lulars. El model captura comportaments cel·lulars genèrics i, en particular, la inhibició de la motilitat per contacte. Es mostra com aquesta interacció dóna una repulsió efectiva entre cèl·lules. Després, s'estudia l'escampament de monocapes epitelials en base a un model continu basat en la teoria dels gels polars actius. Primer es mostra que, a diferència del que passa en l'escenari clàssic, la transició de mullat d'un teixit té un radi crític determinat per les forces cel·lulars actives. Finalment, es prediu que, a causa de les forces de tracció, el front d'una monocapa en expansió, fet que explica observacions experimentals.
http://hdl.handle.net/2445/119579
http://hdl.handle.net/10803/461383
Forces and flows in cells and tissues. Blebs, active gels, and collective cell migration
oai:diposit.ub.edu:2445/1257722024-03-12T17:02:13Zcom_2445_34657col_2445_106688
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Conde Rubio, Ana
author
2018-09-13
[eng] This thesis is devoted to the nanofabrication, simulation and optical characterization of different plasmonic nanostructures.
When an electromagnetic wave reaches a metallic nanostructure, it can give rise to collective oscillations of the free electrons in the metal. These oscillations reach a maximum at the so-called surface plasmon resonance, whose intensity and frequency depend in the material, geometry, embedding medium, interparticle interactions, etc.
Based on the tunability of core-shell nanoparticles, hollow cylindrical gold nanostructures (nanocups) have been fabricating using a combination of nanoimprint lithography (NIL) and non-directional metallization. Besides, to overcome the high-aspect ratio limitations of NIL, a trilayer stack (resist-oxideresist) has been used in such a way that the bottom resist layer, which controls the height of the nanostructure, is not affected by the lithography, which takes place only in the top resist layer. Also, the fabrication method allows for easy changes in the geometry: the height can be changed by changing the thickness of the bottom resist layer, the thickness by modifying the amount of deposited material and the diameter by changing the etching time. By hanging the geometric parameters of the nanostructures, the plasmonic properties can be easily tuned. Besides, for certain dimensions (400 nm in diameter and height and 30 nm of Wall and base thickness), these structures present a peak in the extinction spectra in the visible range that corresponds to a concentration of the electric field within the cavity. This excitation mode has also been reported for other nanostructures with semispherical symmetry. However, the fact of being cylindrical enables a homogeneous enhancement of the electric field along the cavity while in the other case this is not possible due to the lack of symmetry.
Also, based on geometrically frustrated magnetic systems, three particular cases of hexagonal lattices of plasmonic nanoelements have been studied. All of them have been designed so that the pitch is of the order of the resonance wavelength and the gaps between elements small enough to enable near-field coupling. Besides, a metal-insulator-metal configuration has been implemented, designed to have constructive interference, which leads to high absorption peaks.
The samples have been fabricated by electron beam lithography to be able to change easily the design and study the optical response as a function of the geometries. Both simulation and spectroscopy results show that all these systems present high absorption peaks in the visible and/or near infrared. Also, they present a broad absorption peak in the NIR due to the dipolar excitation of the gaps between neighboring elements and sharper peaks in the visible that are assigned to collective modes. Moreover, these systems present an extended time response where the system fluctuates between collective and localized modes. This behavior, characteristic from magnetic frustrated systems, is induced by the frustration of the dipolar excitation of the gaps due to the geometry of the lattice. Besides, the collective modes give rise to enhancements of the electric field in large areas, making these systems of interest for enhanced spectroscopies.
[spa] Esta tesis está dedicada a la nanofabricación, simulación y caracterización de las propiedades ópticas de diferentes nanoestructuras de oro.
Por un lado, inspirados por las nanopartículas tipo core-shell, se han fabricado nanoestructuras de oro cilíndricas en forma de taza, combinando litografía por nanoimpresión (NIL) con metalización por pulverización catódica. Para tener la posibilidad de fabricar estructuras de una elevada altura frente a su anchura, se ha utilizado una tricapa de resina-óxido-resina, de manera que la capa inferior de resina controla la altura de las estructuras mientras que la litografía se realiza en la capa superior y por tanto se sobreponen las típicas dificultades que aparecen en NIL para estructuras de elevada relación de aspecto. Estas nanoestructuras, al igual que las nanoparticulas core-shell, presentan tambien gran capacidad de ajuste de sus propiedades como función de su geometria.
Por otro lado, basados en los sistemas magnéticos con frustración geometrica, se han estudiado diferentes redes hexagonales de nanoelementos de oro. Todos los sistemas se han diseñado de modo que el periodo es del orden de la longitud de onda de resonancia y los espacios entre estructuras suficientemente pequeños para tener acoplo de campo cercano. Se ha utilizado una configuración metal-aislantemetal para obtener interferencia constructiva y, en consecuencia, picos de alta absorción. Las muestras se han fabricado utilizando litografía por haces de electrones para poder estudiar los cambios en la respuesta óptica en función de la geometría. Estos sistemas presentan un pico de absorción ancho en el infrarrojo ligado a la excitación dipolar de los huecos entre nanoestructuras y picos más estrechos en el visible que corresponden a modos donde predomina el comportamiento colectivo del sistema. Además, el estudio de la evolución temporal del sistema muestra que este tipo de redes presentan una respuesta extendida en el tiempo inducida por la frustración geométrica del sistema, característica de los sistemas magnéticos frustrados, durante la cual el sistema oscila entre modos localizados y modos colectivos. Por todo ello, consideramos que estas estructuras pueden ser de interés para aplicaciones relacionadas con la absorción de luz.
http://hdl.handle.net/2445/125772
http://hdl.handle.net/10803/663481
Nanofabrication, simulation and optical characterization of plasmonic nanostructures
oai:diposit.ub.edu:2445/1264502024-03-12T17:02:13Zcom_2445_34657col_2445_106688
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Codina Sala, Joan
author
2018-10-09
[eng] In this thesis we asses the phenomena of arising interactions in soft matter in coexistence with soft active matter. As a non-equilibrium bath we introduce ensembles of self-propelled particles, granular shaken beds, and photo active catalytic particles. We start the thesis with a detailed study of the widely used Active Brownian Particle (ABP) model. This model exhibits a non-equilibrium phase transition which has been intensively studied in recent years, we have finally reported that this transition satisfies all features of equilibrium first order phase transitions. Then, we introduce aligning interactions in ABP and characterize the emergent collective phenomena. In parallel, we explore the emergent forces, from mechanical contact forces, in probe particles in suspensions of aligning active particles and horizontally shaken granular beds. We characterize the forces and identify the emergence of long range interactions in both systems, in aligning active particles long range attractive interactions appear as alignment is increased, and in granular shaken media when the pair of particles align in the shaking direction. Finally, we conclude this thesis with the study of emergent interactions in spherically symmetric systems of catalytic active particles. Symmetry does not permit such particles to propell but the symmetry is broken with the addition of neighboring particles. We model the pair interaction in terms of the relative velocity between particles, and proceed to explore the emergent structures in mixtures of catalytic magnetic particles, and passive particles. We have unveiled the formation of clusters of passive particles. The addition of magnetic interactions between active particles leads to the formation of ramified gel-like structures for dense configurations of active particles. In this case, experimentalists have checked the formation of structures with the same morphologies in experiments in the laboratory.
[spa] En aquesta tesi abordem el fenomen de les interaccions emergents en matèria tova en coexistència amb matèria tova activa. Com a sistemes de matèria tova activa introduïm col·lectius de partícules autopropulsades, col·loides amb capacitat de catalitzar productes químics i medis granulars agitats. Primer de tot estudiem en detall un model molt estès per a partícules actives, el model de les partícules actives brownianes (ABP). D'aquest model estudiem amb detall una transició de fase de no equilibri i comprovem que la transició satisfà amb les característiques d'una transició en equilibri de primer ordre. Seguidament incorporem interaccions d'alineació en el model de partícules actives i procedim a estudiar les propietats col·lectives de les suspensions de partícules actives amb alineació. Per tal d'abordar l'objectiu de la tesi introduïm partícules de prova en suspensions de partícules actives, i en medis granulars amb forçament periòdic horitzontal, amb diferents paràmetres d'activitat per tal d'estudiar les forces, des d'un punt de vista mecànic, que emergeixen entre les parelles. Hem caracteritzat les forces i hem identificat l'aparició d'interaccions de llarg abast per sistemes de partícules amb alineació i en sistemes granulars en la direcció del forçament. Finalment, tanquem la tesi amb l'estudi i modelització d'interaccions emergents per a partícules catalítiques amb simetria esfèrica. La simetria no permet a les partícules d'autopropulsar-se però la presència de partícules al seu entorn sí que dóna lloc a interaccions, en forma de velocitats induïdes. Amb un model raonable de la interacció a distància hem calibrat la magnitud de la interacció amb sistemes experimentals i procedit a caracteritzar les estructures emergents per a mescles de partícules actives i passives que van des de la formació d'agregats en forma de clústers. L'addició d'interaccions magnètiques entre partícules actives permet la formació d'estructures ramificades de tipus gel. En aquest cas l'equip experimental ha pogut comparar l'aparició d'estructures amb les mateixes característiques al laboratori.
http://hdl.handle.net/2445/126450
http://hdl.handle.net/10803/663988
Activity Mediated Interactions in Soft Matter. Structure, Interactions, and Phase Transitions
oai:diposit.ub.edu:2445/1346972024-03-12T17:02:13Zcom_2445_34657col_2445_106688
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Martínez Monge, Álvaro
author
2019-05-28
[eng] Single-molecule experiments have emerged as a powerful tool that allow researchers to investigate the physical behavior of individual molecules with unprecedented resolution. The feasibility exerting forces at the piconewton scale (10^-12 N) and measuring nanometric displacements in the sub-millisecond scale, offer a widespread range of exciting possibilities. The major part of this thesis is devoted to address fundamental topics of statistical physics using single-molecule experiments. In particular, in the first part of the thesis, we aimed to study one of the eldest questions in statistical mechanics: the issue of ensemble inequivalence. By performing single- molecule experiments on a well-known molecule (the CD4 DNA hairpin), we have been able of exploring two conjugate ensembles: the fixed-extension and the force-fixed ensemble. Both ensembles are conjugate with respect to energy since the product force times extension equals has energy dimensions. We carried out experiments in the fixed-force ensemble using both optical tweezers and magnetic tweezers, and in the fixed-extension using optical tweezers. We have found that these two conjugate ensembles are not equivalent at the level of thermodynamics nor in kinetics. Moreover, we showed that the often-neglected boundary terms in the definition of the thermodynamic work are essential to the validity of the fluctuation theorem. The second part of this thesis is also merely theoretical. Recent single-molecule assays confirmed the connection between information theory and statistical physics. Single- molecule experiments have turned out to be the perfect playground to explore the thermodynamic implications of having —or lacking— information. It is worthwhile to mention the experimental realization of the Szilard engine and the experimental verification of Landauer’s limit. With the current existing results, the information-to- energy connection is well established. We have been able to experimentally demonstrate, for the first time, the reversed implication. We have been able to quantify the information-content of neutral molecular ensembles by means of thermodynamic measurements. That is, we experimentally demonstrated the energy- to-information conversion. Our works are built on what we call ensemble force spectroscopy, a systematic procedure capable of obtaining a robust characterization of molecular ensembles in the best tradition of statistical physics, by measuring few tens of molecules. In the final part of the thesis we aimed to measure the specific binding energy of a metallic ion to the tertiary structure of a three-way RNA junction belonging
to the central domain of the 16S ribosomal RNA (rRNA). From the physics perspective, to the best of our knowledge, first time we have been able to discern the free energy contribution due to the specific binding of magnesium ions to an RNA substrate by means of single-molecule assays. On the other hand, such molecule is able to form, besides its native conformation, a force-induced misfolded state. Despite this fact was already pointed out in previous single-molecule studies, there was a lack of knowledge regarding the molecular kinetics and the folding pathway. Aiming to fill this gap, we performed a thorough study of the three-helix RNA junction using dynamic force spectroscopy. As a result, we have characterized the full folding pathway of the molecule, including both the native and the misfolded structure. Furthermore, we have experimentally confirmed the fact that the presence of magnesium promotes the stabilization of the native structure and we have measured this contribution. We have found that magnesium is able to rescue the native structure from the misfolded structure via electrostatic interactions due to magnesium binding. This fact is biologically relevant, since we have been able to characterize the conditions in which a misfolded molecule is able to recover its native conformation.
[spa] En esta tesis hemos abordado cuestiones fundamentales de la física estadística. En particular, hemos estudiado el problema de la equivalencia entre colectivos estadísticos, la conversión de energía a información y el estudio de las energías específicas de unión de iones metálicos a sustratos de RNA. Esta tesis doctoral se ha llevado a cabo empleando dos de los instrumentos de molécula individual más conocidos, las pinzas ópticas y las pinzas magnéticas. Ambas son técnicas que permiten la aplicación controlada de fuerzas mecánicas a los extremos de una molécula individual. El poder aplicar fuerzas a sistemas moleculares permite llevar a cabo una profunda caracterización de las propiedades físicas de los llamados sistemas pequeños. Las dimensiones de estos sistemas abarcan desde unos pocos nanómetros —una millonésima parte del metro— hasta varios cientos de nanómetros. Además, los sistemas pequeños están lejos del llamado límite termodinámico y están dominados por las fluctuaciones térmicas del entorno. Por lo tanto, debido a estas peculiaridades, el estudio de sistemas pequeños mediante los instrumentos de molécula individual permite impulsar y extender los horizontes de la física de no equilibrio.
http://hdl.handle.net/2445/134697
http://hdl.handle.net/10803/667026
Free energy and information-content measurements in thermodynamic and molecular ensembles
oai:diposit.ub.edu:2445/1445382024-03-12T17:02:13Zcom_2445_34657col_2445_106688
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Walther, Jürgen
author
2019-10-04
[eng] The study of DNA from atomistic to mesoscopic level and connecting different resolution levels constitutes a major challenge since the new millennium. In the early 2000s, experiments could resolve for the first time the structure of the nucleosome in high detail or capture physical contacts in the genome of segments far apart in sequence. At around the same time, the force field development for atomistic nucleic acid simulations reached a peak with parmbsc0 in 2007 and coarse grain nucleosome fiber models emerged. The first decade ended with a remarkable experimental advance in visualizing the whole genome, Hi-C. In the current decade, almost ten years after Hi-C was invented, the structure of the cell nucleus is still a very hot topic. We can now harvest the fruits of the pioneers in the first decade of multi-scale investigation of DNA and connect the different resolution levels to obtain a complete picture of DNA from electron orbitals to genome folding.
In this work, we use computational approaches to dissect the different resolution levels, from atomistic MD simulations to mesoscopic secondary chromatin structure modeling. We developed a force-field (parmbsc1) for the accurate description of atomistic DNA dynamics based on quantum mechanical simulations. With the accuracy of parmbsc1, sequence-dependent effects of B-DNA flexibility beyond the base pair level were described and used as a starting point to parametrize a novel helical coarse grain model which shows similar accuracy to the DNA dynamics obtained by atomistic MD, but at much lower computational cost. In a newly developed nucleosome fiber model the coarse grain DNA algorithm is used for the linker DNA description and alongside with a simple mesoscopic characterization of the nucleosome chromatin dynamics can be probed at kilobase scale with a DNA model whose roots lie in the quantum mechanical regime.
On top of that, to meet current standards of accessibility and usability of tools, the developed coarse grain DNA and nucleosome fiber model are freely available as stand-alone versions or integrated in a single webserver or large-scale online research environment platform.
[spa] El estudio del ADN desde la escala atómica a la mesoscópica y la conexión entre dichos niveles de resolución constituye uno de los desafíos mayores del nuevo milenio. Desde el inicio del siglo XX, diversos experimentos han permitido elucidar la estructura del nucleosoma a escala atómica, y por otro lado capturar los contactos entre segmentos del genoma cuyas secuencias se encuentran muy alejadas. En paralelo, el desarrollo teórico de campos de fuerza para la simulación de sistemas atomísticos de ácidos nucleicos logró su primera madurez con la publicación de parmbsc0 en 2007, al tiempo que empezaron a salir publicados los primeros modelos de grano grueso para representar fibras de nucleosomas. La primera década del presente milenio termina con uno de los experimentos más destactados a la hora de visualizar el genoma completo: Hi-C. Actualmente, a casi 10 años del advenimiento del Hi-C, la estructura del núcleo celular sigue siendo un campo muy activo. Es ahora el momento justo para cosechar de los frutos plantados por los pioneros una década atrás y trabajar en la conexión entre los diferentes niveles de resolución logrando una imagen completa y global del ADN en el núcleo celular desde los electrones hasta los cromosomas.
En este trabajo, usamos una aproximación computacional para integrar los diferentes niveles de resolución, desde simulaciones atomísticas de Dinámica Molecular hasta el modelado de fibras de cromatina. Desarrollamos un campo de fuerza atomístico (parmbsc1) que reproduce de forma exacta la dinámica del ADN, basado en cálculos de mecánica cuántica. Gracias a la exactitud de parmbsc1, los efectos estructurales secuencia-dependientes a nivel atómico fueron capturados y usados como parámetros para desarrollar un nuevo modelo helicoidal de grano grueso que ha mostrado una exactitud similar con un coste computacional mucho menor. En el modelo de fibra de cromatina, el modelo de grano grueso mencionado anteriormente es usado para simular el comportamiento del ADN “linker” (libre) entre los nucleosomas que son representados de forma simple pero que permiten estudiar fibras a la escala de kilobases con un modelo basado en la mecánica cuántica.
Sumado a lo anterior, y para hacer nuestros modelos y herramientas disponibles y accesibles de acuerdo a los estándares actuales, los modelos y métodos desarrollados en esta tesis se distribuyen de forma libre como una versión “stand-alone” o integrado en una plataforma de investigación online.
http://hdl.handle.net/2445/144538
http://hdl.handle.net/10803/667845
Revealing DNA dynamics from atomistic to genomic level by multiscale computational approaches
oai:diposit.ub.edu:2445/1473442024-03-12T17:02:13Zcom_2445_34657col_2445_106688
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Estévez Priego, Estefanía
author
2019-11-22
[eng] This thesis was part of the European consortium MESOBRAIN, a team of 5 organizations that joined efforts in nanofabrication, cell culturing, imaging and data analysis to build tailored human 3D networks. The thesis timing was limited to 3 years, and several of the resources needed for its development were built from scratch.
The main objective of this Ph.D. thesis was to explore complex characteristics of cortical neuronal cultures in terms of effective connectivity and exhaustive network analyses. This objective comprised four research lines: (i) The evaluation of neuronal network resilience and emerging plasticity mechanisms, (ii) the characterization of functional development to underline crucial timepoints in healthy neuronal networks, (iii) the study of 3D network interactions of neurons embedded inside an ECM--like environment, and (iv) the design, construction and viability inspection of neurons seeded on tiny 3D nanoprinted solid scaffold structures as a first step towards recreating cortical columns in vitro.
For these multiple lines, we used either primary rat cultures (i,iii,iv) or human--derived neurons (ii). The former group corresponds to cultures with long established protocols that have been thoroughly studied in the field. The latter group corresponds to human neurons derived from iPSCs, a relatively novel model with promising and thrilling applications in regenerative medicine. Despite the increasing use of stem cells in neuroscience, complex systems and medicine, they still lack a thorough exploration in terms of neuronal and circuit formation as well as the properties of the emergent activity patterns.
With either primary or stem cells, we explored the formation of neuronal circuits in 2D and 3D, characterized the effective connectivity and rendered a number of network traits. This Thesis combines experiments of highly difficult implementation with detailed data analysis. It was necessary to develop brand new protocols for culturing 3D neuronal networks and for human-derived neurons, the use of different microscopy setups the programming of object detection and tracking software and advance the analysis toolbox of calcium fluorescence data.
First, resilience experiments on primary clustered neuronal cultures consisted on progressive perturbations through chemical receptor antagonists. This study represents an inspiring numerical--experimental model to comprehend the impact of plasticity mechanisms in the spontaneous activity of neuronal circuits. The results showed that, upon progressive connectivity blockade through chemical receptors' antagonists, only--excitatory neuronal networks displayed a surprising hyper--efficiency (HE) state for early--onset doses. As plasticity mechanisms influence the response of effective connectivity in the presence of perturbations, these compensatory mechanisms, usually disregarded, must be included in biological modeling as accurately as possible. Otherwise, episodes of functional rewiring and synaptic strengthening could mask important phenomena during experiments that alter channel communication. A simple algorithm that hypothesized an effective synaptic scaling was able to capture the hyper--efficiency state seen in experimental data, while percolation models wrongly predicted a progressive decay.
The second research line was a sum of engineering efforts within the MESOBRAIN consortium, the European adventure to build 3D neuronal cultures embedded in hydrogels and with the presence of scaffolds. After several months of biomaterials testing, the candidate D--Clear resulted suitable for the construction of scaffolds, both with primary rat cells and hiPSCs, due to its good optical properties, manageability and biocompatibility. To our knowledge, D--Clear was never used before outside the orthodontic field and could provide a new catalogue of interesting designs for support and guidance of neuronal assemblies. Using this material, we developed a series of designs to offer support and guidance to cortical neurons in a 3D platform.
The third research line focused on the study of neuronal development and cell-to-cell interactions in a semi-synthetic hydrogel that resembles the extracellular matrix of the brain. These hydrogel cultures keep the advantages of in vitro models while achieving an effective connectivity and architecture closer to in vivo.
Finally, the fourth line of research applied cortical neurons from human-derived pluripotent stem cells to study key developmental stages and characterize the healthy maturation of these cells in vitro. As this technology has tremendous potential for regenerative medicine and to model neuronal diseases, it is urgent to consolidate the capacity of these human neuronal networks to reproduce efficient activity patterns of healthy patients, and explore the differences against the results obtained with animal models.
[spa] La presente tesis doctoral se enmarca en el contexto de la Física de la Materia Condensada, la Biofísica y la Neurociencia. Principalmente, se centra en el estudio de la conectividad funcional en cultivos neuronales bidimensionales (2D) y tridimensionales (3D). El trabajo se ha desarrollado en el Laboratorio del director de tesis Dr. Jordi Soriano, en la Facultad de Física de la Universitat de Barcelona, junto con el codirector Dr. Daniel Tornero, en el Hospital Clínic de Barcelona. Esta tesis forma parte del proyecto europeo MESO-BRAIN, del programa Future and Emergent Technologies (FET) de la Comisión Europea, Horizon2020.
El trabajo de investigación combina experimentos con cultivos neuronales (de rata embrionaria o células humanas pluripotentes) y un análisis detallado en el contexto de teoría de redes y sistemas complejos. Los principales núcleos del trabajo realizado son los siguientes: (i) Actividad funcional en cultivos de redes neuronales y los mecanismos homeostáticos que emergen en presencia de perturbaciones; (ii) el desarrollo de herramientas de neuroingeniería para preparar cultivos ad hoc con conectividad dirigida mediante scaffolds; (iii) el análisis exhaustivo de los procesos de formación y madurez de redes funcionales humanas obtenidas de células madre pluripotentes inducidas, una nueva tecnología que promete revolucionar el campo de la medicina regenerativa; y (iv) la caracterización de cultivos neuronales 3D en estructuras que imitan la matriz extracelular natural de su entorno. Entre las diversas técnicas para la realización de cultivos tridimensionales, destacan los hidrogeles semi-sintéticos, constituidos en base a polímeros altamente hidratados con alta biocompatibilidad y cuyas propiedades mecánicas pueden ser manipuladas para obtener la estructura óptima según el tipo de tejido.
En conjunto, los resultados de la presente tesis muestran la gran versatilidad de los cultivos neuronales y aportan avances relevantes en el estudio de plasticidad en redes neuronales, madurez y desarrollo tanto en 2D como en 3D, con sus correspondientes diferencias, incluyendo el uso de neuronas humanas derivadas de células madre inducidas. En el futuro, estos estudios nos permitirán incrementar nuestro conocimiento sobre el funcionamiento global del cerebro y avanzar en la investigación de diferentes enfermedades neurodegenerativas.
http://hdl.handle.net/2445/147344
http://hdl.handle.net/10803/668218
Dynamics and Effective Connectivity in Bi- and Three–dimensional Neuronal Cultures: from Self–organization to Engineering
oai:diposit.ub.edu:2445/1487392024-03-12T17:02:13Zcom_2445_34657col_2445_106688
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Massana-Cid, Helena
author
2019-12-11
[eng] In this thesis we investigate the structure formation and the out-of-equilibrium dynamics of driven and active magnetic colloids. The interactions in our system were tuned in situ by using external fields, with the aim of finding novel approaches to drive and engineer these microparticles into a rich variety of microstructures. The colloids formed chains and clusters able to transport cargos, space-filling gels and self-healing crystals. Moreover, we demonstrated the bidirectional transport of paramagnetic particles on top of a structured magnetic substrate. Because of their associated length-scale, colloids are experimentally accessible with traditional optical microscope techniques. We analysed the data extracted from digital video microscopy and used such information to infer the particle dynamics. Colloids have been proven to be excellent model systems for structures across different length scales that are more difficult to observe, such as collections of atoms and molecules. Furthermore, they are helpful test-beds to investigate fluid dynamics at low Reynolds number and can form artificial micromachines that are essential for the realization of disparate functional tasks at the microscale.
[cat] En aquesta tesi hem investigat la dinàmica fora de l'equilibri de col·loides magnètics i el seu comportament individual i col·lectiu. Controlant les interaccions utilitzant camps magnètics externs i l'activitat química de col·loides especialment sintetitzats, vam construir microdispositius nedadors capaços de transportar altres materials i formar cadenes, agrupacions, gels, i cristalls amb l'habilitat de reordenar-se. A més, vam demostrar el transport bidireccional de partícules paramagnètiques sobre un substrat magnètic. A causa de la seva mida, els col·loides són fàcilment accessibles experimentalment i es poden observar amb microscopis òptics tradicionals. Mitjançant tècniques de videomicroscopia, vam obtenir informació sobre la dinàmica fora d'equilibri dels sistemes estudiats. S'ha demostrat que els col·loides poden ser sistemes model excel·lents per estructures amb diferents escales de longitud que són més difícils d’observar. D'altra banda, els col·loides ens van ajudar a comprendre la dinàmica de fluids a baix nombre de Reynolds, el que té aplicacions en estudis de microfluídica. Aquest treball és un pas més que ens acosta a trobar un microdispositiu òptim basat en partícules col·loïdals per manipular, transportar i controlar processos a aquestes escales.
http://hdl.handle.net/2445/148739
http://hdl.handle.net/10803/668374
Out-of-equilibrium dynamics in driven and active magnetic colloids
oai:diposit.ub.edu:2445/1858282024-03-12T17:02:13Zcom_2445_34657col_2445_106688
00925njm 22002777a 4500
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Gràcia Condal, Adrià
author
2022-04-21
[eng] The urgent need to reduce our footprint on the earth environment is leading to ever more stringent commitments to decrease greenhouse gases emissions, which entails one of the greatest challenges that mankind has to tackle. As a direct consequence, it is of utmost importance to develop novel, energy-efficient and environmentally-friendly refrigeration technologies that do not require the use of climate-damaging substances. In this regard, solid-state refrigerants based on the large thermal response exhibited by a variety of materials when field-inducing a ferroic phase transition are among the best alternatives. Specifically, materials undergoing a first-order phase transition are of particular interest as the latent heat associated with the phase transition contributes on enhancing the magnitude of the thermal response. Depending on the nature of the external field that drives the phase transition one distinguishes between magnetocaloric, electrocaloric, elastocaloric or barocaloric effects. In spite of all the intensive research devoted to the study of the diverse caloric effects, there are still a series of bottlenecks to overcome. Firstly, they require the application of strong external fields in order to induce a large thermal response. Secondly, the hysteresis associated with the phase transition can drastically reduce the efficiency and compromises its reversibility. A way out of such issues can be provided by materials exhibiting a strong coupling between the structural, magnetic or electronic degrees of freedom, denoted as multicaloric materials, which allow to drive their phase transition by the combination of diverse external fields, giving rise to multicaloric effects. Despite the high potential they exhibit, the research on multicaloric materials is germinal as it requires the use of non-commercial experimental systems. In this dissertation, we have focused on the study of materials displaying a magnetostructural first- order phase transition with a strong coupling between the structural and magnetic degrees of freedom. For such purpose, we have used distinct purpose-built calorimetric and adiabatic thermometry systems to investigate their caloric and multicaloric effects by direct methods. We have concentrated on two distinct families of multicaloric materials: Fe-Rh and Ni-Mn-based Heusler alloys. Our research is aimed at thoroughly characterizing the diverse advantages of multicaloric effects: showing that lower driving fields are required, that the operating temperature windows of the materials can be enlarged and discussing how their inherent hysteresis can be mastered or even exploited.
[cat] La necessitat urgent de reduir la nostra empremta en el clima s’està materialitzant en compromisos globals per disminuir l’emissió de gasos d’efecte hivernacle que cada cop son més estrictes, representat avui en dia un dels majors reptes que la humanitat ha d’afrontar. Com a conseqüència directa, és de la màxima importància desenvolupar noves tecnologies de refrigeració que siguin eficients i respectuoses amb el medi ambient. En aquest sentit, entre les millors alternatives es troben els refrigerants en estat sòlid basats en materials que presenten una resposta tèrmica gran quan s’indueix una transició de fase ferroica mitjançant un camp extern. En concret, són d’especial interès els materials que presenten una transició de fase de primer ordre, ja que la calor latent associada a la transició de fase incrementa la magnitud de la resposta tèrmica. Depenent de la naturalesa del camp extern que s’utilitza per induir la transició de fase, es distingeix entre els efectes magnetocalòric, electrocalòric, elastocalòric o barocalòric. Malgrat els grans esforços dedicats en l’estudi dels diversos efectes calòrics, hi ha una sèrie d’obstacles que cal superar. En primer lloc, es necessiten camps intensos per induir una resposta tèrmica gran. En segon lloc, la histèresi associada a la transició de fase pot reduir dràsticament la seva eficiència i comprometre la reversibilitat de l’efecte calòric. Una possible sortida a aquests problemes pot venir donada pels materials que presenten un fort acoblament entre els graus de llibertat estructural, magnètic o electrònic, anomenats materials multicalòrics, ja que permeten que la seva transició de fase s’indueixi mitjançant la combinació de diversos camps externs, donant lloc als anomenats efectes multicalòrics. Malgrat l’alt potencial que presenten a l’hora d’abordar algunes de les mancances que s’han posat de manifest ens els diversos efectes calòrics, l’interès en la seva recerca és molt recent ja que requereix l’ús de sistemes experimentals no comercials. En aquesta tesi, ens hem centrat en l’estudi de materials que presenten transicions magnetoestructurals de primer ordre amb un fort acoblament entre els graus de llibertat magnètic i estructural. Amb aquest propòsit, hem utilitzat diversos dispositius experimentals dissenyats ad hoc que permeten realitzar mesures calorimètriques o termomètriques sota la influència de camp magnètic i esforç uniaxial per tal de caracteritzar-ne els efecte calòrics i multicalòrics mitjançant mètodes directes. Ens hem centrat en dues famílies de materials multicalòrics: Fe-Rh i aliatges tipus Heusler de base Ni-Mn. La recerca duta a terme s’ha centrat en caracteritzar a fons els diversos avantatges que presenten els efectes multicalòrics: demostrant que requereixen camps de menor intensitat per induir una resposta tèrmica gran, que permeten ampliar el rang de temperatura de treball dels materials o que proporcionen estratègies per controlar o fins i tot aprofitar la histèresi associada a la transició de fase.
http://hdl.handle.net/2445/185828
http://hdl.handle.net/10803/674290
Giant caloric and multicaloric effects in magnetic alloys
oai:diposit.ub.edu:2445/1895222024-03-12T17:02:13Zcom_2445_34657col_2445_106688
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Mercadal Melià, Josep
author
2022-06-16
[eng] The development of living systems, from their conception to their death, involves a very tight coordination between gene expression in time and space. The processes involved in such an unfolding do not solely depend on the interactions between genes, but also on the environment the organism is embedded in, partly random and unpredictable, partly constructed by the organism itself. Indeed, no embryo grows without a warm womb or a protected egg. Understanding development is understanding how diverse functions or phenotypic traits arise from these relationships.
In this thesis we have studied some of these biological processes mainly in plants. The approach we take to these problems is that of systems biology, the theoretical framework that studies the interactions between the constituent parts of organisms, be they molecules, genes or cells, and how these relations lead to emergent behaviours which cannot be understood through the study of the parts alone. The main goal is to understand, through this theoretical approach, the biological processes involved in cellular decision-making, whether they are related to the division, differentiation, or generation of molecular signals.
The first part of the thesis focuses on the regulatory interactions between BRAVO and WOX5, two transcription factors involved in the regulation of quiescent cells in the stem cell niche of the Arabidopsis thaliana root. By combining theoretical modelling with experimental evidence, we find that these two factors interplay both at the transcriptional and post-transcriptional level, and they involve the formation of a complex. Owing to the convergence of the two transcription factors at the quiescent center, we propose a simple mechanism for regulating cell division and find that the formation of the BRAVO-WOX5 complex can be relevant. We also consider the effect of space in the regulations between BRAVO and WOX5, finding that the movement of WOX5 can be relavant to explain the expression patterns observed experimentally.
The second part has focused on the role of genetic circuits operating in coupled cellular lattices by the diffusion of one of the molecules, and how these interactions can generate spatial patterns of different cell types. We first apply this approach to the formation of rhizoid precursor cell patterns in the epidermis of the Marchantia polymorpha plant. Rhizoids are thin outgrowths which appear at the interface between the plant main body and the substrate, and extend distally into the soil effectively increasing the total surface area for water and nutrient absorption. The formation of rhizoids in the epidermis of Marchantia is known to be regulated by several factors, but how the specific spatial distribution emerges from a field of epidermal cells is poorly understood. Building on recent experiments, we propose that rhizoid patterns appear from the interactions between the microRNA FRH1 and the rhizoid-promoting transcription factor RSL1, in a feedback circuit of activator-inhibitor type, where RSL1 activates FRH1, and FRH1 diffuses and represses the activity of RSL1. We find that our theoretical predictions precisely match those of the experiments, underscoring the capabilities of the model.
We then study the spatiotemporal behaviours of a small genetic circuit capable of displaying diverse spatiotemporal behaviours, including bistability, oscillations and pattern formation. The circuit is based on the mixed feedback loop, a genetic circuit overrepresented in statistical analyses of gene and protein interaction databases. It consists of the transcriptional repression of a gene by another, plus the formation of a reversible complex between the proteins coded by the two genes. Through dynamical systems theory and bifurcation analysis, we find the conditions for each regime to appear and emphasize the multi-functional nature of the circuit, a feature embodying an increasingly common theme in developmental and evolutionary systems biology, namely the importance of small circuits capable of performing multiple, qualitatively different functions, which arise from the circuit’s topology but depend on the specific external context of which the circuit is embedded.
The ultimate goal of systems biology is to understand life at its most basic level. As complex systems par excellence, living organisms have characteristics that cannot be reduced only to the behaviors of their parts. Instead, it is the nature of its systems that characterizes its most iconic idiosyncrasies, from the internal functioning of a cell to the complicated structure of the nervous system.
[cat] El desenvolupament dels éssers vius, des de la seva concepció fins la seva mort, implica una estreta coordinació de l'expressió gènica en el temps i l'espai. Els processos implicats en aquest desplegament no depenen únicament de les interaccions entre gens, sinó també de l’entorn, en part aleatori i impredictible, en part construït pel propi organisme. Cap embrió creix sense un ventre calent o un ou protegit. Entendre el desenvolupament és entendre com les diverses funcions o trets fenotípics sorgeixen d'aquestes relacions.
En aquesta tesi hem estudiat alguns d’aquests processos biològics principalment en plantes. L’enfocament amb el qual afrontem aquests problemes és el de la biologia de sistemes, el marc teòric que estudia les interaccions entre les parts constituents dels organismes, siguin molècules, gens o cèl·lules. L’objectiu principal és entendre, mitjançant aquest enfocament teòric, els processos biològics involucrats en la presa de decisions cel·lulars, ja estiguin relacionades amb la divisió, la diferenciació, o la generació de senyals moleculars.
La primera part de la tesi es centra en les interaccions reguladores entre BRAVO i WOX5, dos factors de transcripció implicats en la regulació de les cèl·lules quiescents al nínxol de cèl·lules mare de l'arrel d'Arabidopsis thaliana.
La segona part s'ha centrat en el paper dels circuits genètics que operen en xarxes cel·lulars acoblades per la difusió d'una de les molècules, i com aquestes interaccions poden generar patrons espaials de diferents tipus cel·lulars. Apliquem aquest enfocament a la formació de patrons de cèl·lules precursores de rizoides a l'epidermis de la planta Marchantia polymorpha, per una banda, i en un circuit genèric multifuncional, per l’altra.
L'objectiu final de la biologia de sistemes és entendre la vida en el seu nivell més fonamental. Com a sistemes complexos per excel·lència, els organismes vius presenten característiques que no es poden reduir només als comportaments de les seves parts. En canvi, és la naturalesa dels seus sistemes la que caracteritza les seves idiosincràsies més icòniques, des del funcionament intern d'una cèl·lula fins a l'estructura complicada del sistema nerviós.
http://hdl.handle.net/2445/189522
http://hdl.handle.net/10803/675535
Nonlinear and spatial dynamics for multicellular organisms
oai:diposit.ub.edu:2445/1898422024-03-12T17:02:13Zcom_2445_34657col_2445_106688
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Fernández i Gallén, Andreu
author
2022-07-08
[eng] Membranes are present in all cells, in some viruses, and are involved in all kinds of biological functions. The goal of this thesis is to expand our knowledge of this element, in hope that this -on top of all the other knowledge of biology and physics- can help someday improve people's life.
With this aim, what I tried to do was to understand how cells react when things happen to them. This is the drive behind the two different research paths written in this thesis: membranes inside a fluid flow, and membranes during topological transitions and fluctuations.
For the first research path -on membranes inside a flow- while this is not a new topic we wanted to start by making it more approachable. That has been achieved by introducing a new methodology to couple membranes and flows by using the stream function and the vorticity to solve the Navier Stokes equation. This approach creates a model derived straight from the hydrodynamic equations and grounded on the physics of the system rather than other more complex approaches.
With this model we tried to study the effects of confinement for membranes inside a Poiseuille flow. We mainly tried to replicate red blood cell shapes as it is a very researched case and there is plenty of experimental data on them. First starting with cells inside channels slightly bigger than their diameter, which is known to give a set of shapes named parachutes and slippers. We use this knowledge to prove the validity of our model.
For very wide channels, the low confinement Poiseuille flows have shown a different meta-stable shape which we named anti-parachute. Moreover, tumbling can be produced by introducing a different viscosity for the cell fluid, higher than the surrounding fluid.
In very narrow super-confined channels we have a Poiseuille flow where the cell is much bigger than the channel and gives very different shapes.
However, the model is capable of studying other flows rather than Poiseuille. Couette flow has been studied, where one can see a lift perpendicular to the flow that depends on the reduced volume of the cell as well as the viscosity contrast.
The most important thing has been leaving behind a methodology ready for expansion to time-dependent flows, inertial flows, or to generalize to 3 dimensions.
For the second research path --on topological transitions-- we have implemented the Gaussian curvature energy term to the membrane model, to allow study of fission and fusion.
With this methodology we study fission of tubes with the use of the spontaneous curvature, which deforms a membrane tube into a pearled tube. This pearled tube formed by an array of spheres connected through membrane tethers undergoes fission if the Gaussian rigidity is negative and high enough. A phase diagram of what happens depending on the values of Gaussian and bending rigidity is obtained.
Then we expand to study geometries less helpful for fission, such as a flat planar membrane. It will not matter how big is the spontaneous curvature of the Gaussian rigidity, as a perfectly flat membrane is a meta-stable shape. This is due the fact that to start the fission process we need an area with enough curvature so that the spontaneous curvature can kick-off the membrane budding process.
To solve this, we added a white noise to mimic temperature. This noise makes each point of the membrane position to fluctuate. There is a phase transition between a flat membrane that is not undergoing fission and one that does.
[cat] Les membranes estan presents a totes les cèl·lules, en alguns virus, i estan implicades en tot tipus de funcions biològiques. L'objectiu d'aquesta tesi és ampliar el nostre coneixement d'aquest element, amb l'esperança que això –junt amb tots els altres coneixements de biologia i física– pugui ajudar algun dia a millorar la vida de les persones.
Amb aquest objectiu, el que vaig intentar va ser entendre com reaccionen les cèl·lules quan els passen coses. Aquest és el objectiu de les dues parts en les que està dividida la recerca en aquesta tesi: membranes dins d'un flux de fluids i membranes durant transicions topològiques.
Per a la primera part de la recerca –sobre membranes dins d'un flux–, tot i que no és un tema extremadament nou, hem volgut començar per fer-lo més accessible. Això s'ha aconseguit introduint una nova metodologia per acoblar membranes i fluxos. Amb aquest model hem intentat estudiar els efectes del confinament de les membranes dins d'un flux. Tanmateix, el més important ha estat deixar enrere una metodologia preparada per a l'expansió a fluxos dependents del temps, fluxos inercials o per expandir-se a 3 dimensions.
Per a la segona part de la recerca –sobre transicions topològiques– hem implementat el terme d'energia de curvatura gaussiana al model de membrana, per permetre l'estudi de la fissió i la fusió. Amb això s'estudia la fissió de tubs amb l'ús de la curvatura espontània. A partir d'això ens expandim per estudiar geometries menys tolerants per a la fissió, com ara una membrana plana plana. Afegint una temperatura a les simulacions s'estudia com en funció de la temperatura es pot promoure fins i tot una membrana amb geometria difícil per generar vesícules.
http://hdl.handle.net/2445/189842
http://hdl.handle.net/10803/675668
Modelling the dynamics of cellular membranes
oai:diposit.ub.edu:2445/2012052024-03-12T17:02:13Zcom_2445_34657col_2445_106688
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Cereceda López, Eric
author
2023-07-14
[eng] In this thesis, I study the behavior of confined colloidal particles in aqueous suspension driven through an optical potential. For this purpose, I use micro-meter polystyrene particles, which I confine in the optical potential created with a system of optical tweezers.
With the help of an Acousto Optical Deflector (AOD), which varies the laser position at a high frequency, I can create multiple quasi-simultaneous optical traps. This way, I can easily manipulate the particles and define the desired experimental conditions for the potential.
I record videos of the particles' dynamics using optical microscopy. Thus, I obtain position information over time, which allows me to extract the necessary data to analyze the mechanisms that develop during forced transport.
The results presented in this thesis expose the importance of Hydrodynamic Interactions (HI) when the transport of particles occurs due to a fluid drag. In addition, different situations are compared, including the change in the relative particle size concerning the separation between potential wells.
In addition, I present a study on the emergence of solitons propagating in the opposite direction to the drag force. This situation, which appears when the experimental system is overcrowded, presents a mechanism where the transport dynamics accelerate, increasing the systems' efficiency.
[spa] En esta tesis estudio el comportamiento de partículas coloidales en suspensión acuosa cuando son forzadas a moverse a través de un potencial óptico. Para ello, utilizo partículas micro- métricas de poliestireno, las cuales confino en el potencial óptico creado con un sistema de pinzas ópticas.
Con la ayuda de un Deflector Acusto Óptico (AOD), el cual varía la posición del láser a una alta frecuencia, puedo crear múltiples trampas ópticas de manera casi simultánea. Esto me permite manipular las partículas con facilidad y definir las condiciones experimentales deseadas para el potencial.
A través de microscopía óptica, obtengo imágenes en vídeo de la dinámica de las partículas. Así, obtengo la información de la posición a lo largo del tiempo, lo que me permite extraer los datos necesarios para analizar los mecanismos que se desarrollan durante el transporte forzado.
Los resultados expuestos en esta tesis ponen de manifiesto la importancia de las Interacciones Hidrodinámicas (HI) en el transporte de partículas cuando son arrastradas por el fluido. Además, se comparan diferentes situaciones en las que se incluye el cambio en el tamaño relativo de las partículas respecto a la separación entre pozos de potencial.
Además, presento un estudio sobre la aparición de solitones que se propagan en la dirección contraria en la que se ejerce la fuerza de arrastre. Esta situación, que aparece al sobrepoblar el sistema experimental, presenta un mecanismo en el que el transporte de materia se acelera, lo que incrementa la eficiencia.
http://hdl.handle.net/2445/201205
http://hdl.handle.net/10803/688857
Non-Equilibrium Dynamics of Driven and Confined Colloidal Systems