Tamara presents Computational Models of Cell Adhesions Mechanobiology

Abstract. Cell-cell junctions and cell-substrate adhesions are specialized regions of the plasma membrane that couple the cytoskeleton network to the extracellular environment. They are critical in several cell activities, including tissue morphogenesis, homeostasis, migration and wound healing. Central elements of adhesions are transmembrane receptors, that form physical links between cell cytoskeleton and external binding partners: cadherins mediate cell-cell junctions and integrins form cell-substrate adhesions. Cadherin and integrin sense, resist and transmit cytoskeletal contractility. In particular, adhesion resistance to contractility makes cadherin and integrin cell mechanosensors, responding to mechanical signals with specific kinetic activities. Unfortunately, the biophysical mechanisms by which adhesions reinforce in response to stress are not fully understood. In this study, we developed a computational model based on Brownian Dynamics in order to study mechanisms of adhesion reinforcement via two biophysical mechanisms: catch-bond kinetics and clustering. Our model shows that a dynamic interplay between the two biophysical mechanisms can promote adhesions stabilization. Moreover, combination of catch-bond kinetics with receptor clustering allow identifying different regimes of adhesion tension, that are necessary to transmit stresses via junctional tension and cell-substrate interactions. These results provide important insights into the biophysical principles and mechanisms of adhesion mechanosensing, with functional consequences on both cell and tissue physiology.