# name
Optimization of SH-SY5Y  Differentiation to Study Neuronal Mechanosensitivity

# metadata.dc.description[].value
Treballs Finals de Grau d'Enginyeria Biomèdica. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona. Curs: 2022-2023. Tutor/Director: Roca-Cusachs Soulere, Pere, De la Cruz, Jorge Oliver

# metadata.dc.description.abstract[].value
Neurodegenerative disorders, including Alzheimer’s disease, pose a global social burden strongly 
linked with aging populations. Despite extensive research efforts, the underlying causes of the 
neuropathological changes that result in neuronal death are unknown, making the improvement of 
in vitro models a priority to address. Moreover, these pathological events are accompanied by 
alterations in brain rigidity, and while it is well established how various cell types can feel these 
mechanical cues and adapt their function, neuronal mechanosensing remains mostly unexplored.
For this reason, in this project we aimed to investigate the mechanobiology of Alzheimer's disease 
by optimizing the differentiation of SH-SY5Y cells into pseudo-neurons.
To facilitate neuronal differentiation, we adopted a novel strategy in which, by introducing a genetic 
construct in the SH-SY5Y cells, we could control the expression of the neuronal master gene 
NGN2. We demonstrated that this system, along with an optimized differentiation protocol, led to 
the production of more mature neuron-like cells.
Subsequently, the response of differentiated cells to mechanical stimulation was tested by culturing 
them in polyacrylamide gels with varying stiffness. Immunostaining and image analysis confirmed 
the morphological adaptation of neuron-like cells to matrix stiffness, presenting better morphology 
at a higher stiffness. Finally, we observed detectable levels of the co-transcriptional factor YAP and
confirmed that its nuclear presence is mechanoregulated in neurons.
In conclusion, by combining differentiation techniques, genetic modification, and mechanical 
stimulation, our study provides a new model to explore Alzheimer's disease mechanobiology, 
potentially leading to innovative therapeutic strategies by uncovering complex underlying 
mechanisms.

# metadata.dc.rights[].value
cc-by-nc-nd (c)  Hinojosa Grajales, Yara, 2023

# metadata.dc.source[].value
Treballs Finals de Grau (TFG) - Enginyeria Biomèdica

# metadata.dc.title[].value
Optimization of SH-SY5Y  Differentiation to Study Neuronal Mechanosensitivity