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cc by-nc (c) Campàs i Rigau, Otger, 2022
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/191581

From molecular force generation to large scale cellular movements

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[eng] The propulsion mechanisms that drive the movements of living cells constitute perhaps the most impressive engineering works of nature. Still, it is simply the interaction between molecules which is responsible for these complex and robust motility mechanisms. A question that arises naturally is thus how the underlying molecules self-organize to perform such highly coordinated tasks. Although a global understanding of cell behavior is still out of reach, the study of particular aspects of biological systems may help building up a more clear picture. Biologists have made lots of efforts to characterize the proteins involved in cellular movements, to identify their interactions and to understand their regulation. This information is very important and has explained several aspects of the motility of living cells. The discovery of proteins able to generate forces at molecular scales, known as motor proteins, provided essential information to understand the observed cellular movements. However, the force developed at the molecular level by a single protein is too weak to drive cellular movement on its own. Probably the clearest example is the functioning of muscles. The forces developed are about 12 orders of magnitude larger than the forces generated at molecular scales. This is possible because the contraction of muscles involves the collective action of many motor proteins (Alberts et al., 2004; Bray, 1992). Although each one of these proteins generates a small force (in the picoNewton range), the sum of their individual contributions leads to large forces. At the cellular scales something similar occurs. The necessary forces for the motion of a cell and even for intracellular movements, are larger than molecular forces. The collective action of molecular force generators is thus essential to understand most cellular movements. Here we study theoretically some examples of cellular movements and compare quantitatively, when possible, our results to the experimental observations. The work is divided in three parts: we first study the motion of oil drops propelled by an actin comet tail, which closely mimics the motility mechanism of several bacterial pathogens, as the bacteria Listeria. The second part is devoted to particular aspects of intracellular transport. We study the physical mechanism of membrane tube extraction by motor proteins, the traffic of motor proteins at large scales and the collective force generation of molecular motors pulling on fluid membranes. In the last part we address both the motion of chromosomes in eukaryotic cell division and the stability of spindle-like structures, as the mitotic spindle. Our aim is to understand how these movements arise from the cooperative action of molecular force generators. The forces developed by ensembles of force generators are not static, but depend on the dynamic state of the system. This is so because the kinetics of the individual force generators is strongly affected by the forces created by themselves. As we discuss below, this force-dependent kinetics imposes a highly non-linear dynamics for the system and, as a consequence, several dynamic instabilities occur. Our work shows that the collective behavior of molecular force generators is essential to understand some features of cellular movements.

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CAMPÀS I RIGAU, Otger. From molecular force generation to large scale cellular movements. [consulta: 28 de novembre de 2025]. [Disponible a: https://hdl.handle.net/2445/191581]

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