Dynamics of cell-matrix mechanical communication during morphogenesis

PROJECT SUMMARY Tissue and organ development occurs through coordinated cellular processes driven by the interplay of biochemical, mechanical, and spatial signals. However, the mechanisms by which such signals are integrated to produce functional structures remain poorly understood. In particular, we are only beginning to explore the role of extrinsic mechanical signals such as those originating from the extracellular matrix. The long-term goal of my research is to address this knowledge gap by investigating how mechanoregulatory signals control cell and tissue behavior during development. To this end, during this 5-year project, we will focus on dissecting the mechanisms by which mechanical regulation exerted by the extracellular matrix modulates cellular mechanisms of remodeling and adhesion to achieve tissue-level deformations. We will combine powerful optogenetic manipulations together with molecular/genetic perturbations, biophysical measurements and advanced imaging in in vitro and in vivo. Our approach proposes an integral understanding of the dynamic and complex nature of cell-ECM mechanical communication by studying mechano-regulation from multiple angles, ranging from intrinsic ECM mechanical properties (Gap 1: modulation of active tissue-deformation via ECM viscoelasticity) to a mechanistic understanding of cell-ECM signaling models remodeling (Gap 2: Cell-ECM communication mechanisms promoting active ECM remodeling); and adhesion (Gap 3: Interplay of cell-cell and cell-ECM adhesions driving tissue deformations).This work will provide a more comprehensive understanding of the dynamic and complex nature of cell-ECM mechanical communication, which is an essential component to unravel mechanochemical interactions driving the emergence of cell and tissue organization. Ultimately, the understanding provided by these studies will have important implications in two main fronts, first, to mechanistically understand mechanoregulatory signals leading to abnormal events and treat them as potential mechano-targets; and second, to leverage such signals as a means to engineer functional tissues in a predictable fashion for use in regenerative medicine.