Molecular Machinery of Mechano-sensitivity in Cells

University Of California-Davis, Davis CA

Investigators

Abstract

This award supports fundamental research to identify and test molecules essential for cells to respond and adapt to external physical perturbations. The epithelial tissue is a physical barrier that separates the internal structures of the human body from the outside. The epithelial tissues consist of individual cells that are highly inter-connected by cell junctions. These junctions are dynamic, and respond to mechanical perturbations, yet, little is known about how cells sense physical forces at a molecular level. The new strategy generates a spatial map of proteins under different physical perturbations, and identifies unique protein-to-protein interactions that may be responsible for force-sensing. Identification of force-sensitive molecular arrangement is essential for fundamental understanding of tissue mechanics. This interdisciplinary research also supports outreach efforts to promote science careers especially in under-represented groups. Physical force emerged as a key regulator of tissue homeostasis, and plays an important role in embryogenesis, tissue regeneration, and disease progression. Currently, the details of protein interactions under elevated physical stress are largely missing, therefore, preventing fundamental, molecular understanding of mechano-transduction. This research is based on an innovative biochemical strategy to identify force-induced protein interactions surrounding zyxin, a unique force-sensing protein. Using promiscuous biotin ligase to label proximal proteins and cell stretch device to exaggerate forces exerted to cell junctions, the research team will determine how the composition of proteins surrounding zyxin changes with the application of substrate stretch, then test the roles of these proteins during the force-generating events. Furthermore, the precise force-dependent protein-protein interactions will be analyzed using mutational approaches.