(721e) The Effect of Mechanical Load on Collagen Proteolysis by Matrix Metalloproteinase-1

Adhikari, A. S., Stanford University
Chai, J., Stanford University
Dunn, A. R., Stanford University

Both mechanotransduction and ECM remodeling are critically important during embryonic development and in the progression of arthritis, aneurysms, atherosclerosis, and cancer metastasis. Although mechanical stress is known to profoundly influence ECM remodeling, the effect of applied load on ECM degradation by matrix metalloproteinases (MMPs) is largely unexplored. We used a single-molecule magnetic tweezers assay to study the effect of force on collagen proteolysis by MMP-1. Here we show that 10 pN forces (orders of magnitude less than the traction forces exerted by cells) cause a 100-fold increase in proteolysis rates. Our results support a mechanistic model in which collagen triple helix increases in length prior to proteolysis, thus accounting for the surprising degree of force sensitivity. Our data and the resulting model predict that cell-generated traction forces may dramatically increase localized collagen proteolysis rates, suggesting that cells may use mechanical force as a novel means for regulating proteolytic ECM remodeling.