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Hajer Ennomani

Contractile response of biomimetic actomyosin systems

Published on 6 November 2015

Thesis presented November 06, 2015

Cellular contractility - the internal generation of force by a cell orchestrated by the actomyosin machinery - is a critical regulator of a wide range of cellular processes including the establishment of cell polarity, cell migration, tissue integrity or morphogenesis during development. Disruptions of the force generation and of mechanical properties of living cells affect their physiological functions and consequently can lead to pathological defects including cancer. However, the parameters or mechanisms that drive force production by the actin-myosin system and their mode of regulation in cells are not fully understood.
During my PhD, I used biomimetic system made of a minimum set of proteins to study the properties of actomyosin contractile systems The goal was to understand how/if the actin architecture can mediate the contractile response. For this purpose, I was first interested in building a variety of actin organization that will serve next as substrate for myosin during contraction. To understand the general principles that dictate geometrically-controlled actin assembly, we developed a model that allowed us to identify key parameters including filaments/filaments interaction, filament mechanical property and contact activation between actin filaments growing from the adjacent pattern and the nucleation area. These actin templates were used then to evaluate the response of oriented actin structures to myosin-induced contractility.
I demonstrated that crosslinking level modulates the myosin-induced deformation of actin networks according to their architecture. I showed also that cross linkers are necessary to sustain myosin-driven deformation and force production of dynamic actin networks. In addition, we developed numerical simulation in order to relate the observed myosin-driven actin deformation with the underlying microscopic mechanism. This work revealed how diverse cellular actin networks contract differently to a define set of biochemical conditions and hence how dynamic rearrangements can modulate network contractility.

Actin, myosin, contractile​ system, biomimetic system, molecular motor

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