Maximizing force production from molecule to tissue – MaxForce

The mechanical force generated by the acto-myosin system is at the heart 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 and in tissue are not fully understood.

The main objective of our project is to characterize how the composition, the organization and the geometry of the acto-myosin network influence the production of contractile forces. Based on our published and preliminary results, our working hypothesis is that the combination of biochemical and geometrical parameters lead to a contractile force variation that is not monotonic and that thus some force maxima exist. We would like to characterize those parameters and identify the working conditions in which force production is maximal. By performing these analyses at the levels of the acto-myosin network, of the cell and of the tissue, we hope to gain a multi-scale understanding of the mechanisms of force production.

To achieve the goals of our project, we will rely on interdisciplinary approaches in systems of increasing complexity ranging from contractile system reconstituted in vitro from purified proteins (Resp. Laurent Blanchoin), single cells or minimum multicellular systems (Resp. Manuel Théry) and finally in an multicellular system during the development of epithelial tissue (Resp. Yohanns Bellaïche).

Collectively, our work should unveil the general principles that control force scaling and should provide a comprehensive understanding of the conserved mechanisms controlling cell mechanics to regulate cell shape and tissue morphogenesis.