Obscurin Acts as a Variable Force Resistor

Abstract

Obscurin, a giant cytoskeletal protein, functions in part to connect distal elements within a large variety of cell types. Due to this cellular role, obscurin likely changes shape as its molecular targets move throughout the cell. In this way, obscurin must intrinsically resist force. Here, we describe the molecular etiology of force resistance through the study of multiple tandem obscurin Ig domains. Using a combination of experimental and computational techniques, we find that obscurin acts as a differential force resistor. Differences in tandem Ig domain flexibility are dictated primarily by linker sequence and not linker length. These studies provide insight into the basic mechanisms of how cells respond to and resist stretch force.