Co-dynamics of contraction and adhesion in animal morphogenesis – CODAC

During embryonic development, forces produced within single cells are transmitted through adhesive cell-cell contacts to drive multicellular tissue morphogenesis. The protein networks that govern contraction and adhesion are dynamically coupled materials that undergo continuous assembly/disassembly and force-dependent remodeling. How mechanical and biochemical coupling among these networks governs their co-dynamics to ensure robust morphogenetic outcomes remains a major question. We will use C. elegans as a uniquely tractable model system and combinine quantitative multiscale microscopy, genetic perturbations and biophysical modeling to address the following questions: (a) how are shape changes of cell-cell contacts driven by gradients of active contractile stress working against the effectively viscous resistances of contractile and adhesion networks to deformation, detachment, and shear? (b) How do local stress, effective friction and viscosity emerge from, and depend upon, the microscopic architecture and co-dynamics of contractile and adhesion networks? (c ) How in turn are microscopic architecture and co-dynamics shaped by deformation and flow? We expect to determine and understand the molecular underpinnings of key physical parameters, including how the kinetics of association/dissociation of adhesion and contractile networks in vivo define frictional resistance and force transmission across cell contacts, and generate flow at the embryo scale.