Sarcoglycans versus Integrins in Mechanotransduction

Brigham And Women'S Hospital, Boston MA

Investigators

Abstract

DESCRIPTION (provided by the applicant): Cells respond in a variety of ways to mechanical stresses. External sensors for detecting these stresses may include the integrins, protein heterodimers that bind to specific extracellular matrix molecules. The sarcoglycan-dystroglycan complex, a complex of proteins that also connects the extracellular matrix with the cytoskeleton, may also transduce biomechanical signals. Although the roles of integrins and the sarcoglycan-dystroglycan complex in mechanotransduction are unclear, defining the relative contributions of these complexes is a critical component of understanding cellular behavior. By using precisely-controlled forces targeted to the integrins or sarcoglycans, as well as genetically-engineered models, we can explore the roles of these protein complexes in mechanotransduction. The specific aims of this project are: 1 - to characterize the mechanical stimuli required to induce molecular responses in vascular cells, and 2 - to distinguish between the molecular responses of cells when stressed via the integrins versus the sarcoglycan-dystroglycan complex.