Degradability tunes ECM stress relaxation and cellular mechanics

Abstract

In native extracellular matrices (ECM), cells can use matrix metalloproteinases (MMPs) to degrade and remodel their surroundings. Likewise, synthetic matrices have been engineered to facilitate MMP-mediated cleavage that enables cell spreading, migration, and interactions. However, the intersection of matrix degradability and mechanical properties has not been fully considered. We hypothesized that immediate mechanical changes result from the action of MMPs on the ECM and that these changes are sensed by cells. Using atomic force microscopy (AFM) to measure cell-scale mechanical properties, we find that both fibrillar collagen and synthetic degradable matrices exhibit enhanced stress relaxation after MMP exposure. Cells respond to these relaxation differences by altering their spreading and focal adhesions. We demonstrate that stress relaxation can be tuned through the rational design of matrix degradability. These findings establish a fundamental link between matrix degradability and stress relaxation, which may impact a range of biological applications. Table of contentsThis work reveals that matrix degradability, through its effects on stress relaxation, is an important cellular mechanotransduction cue. Cell-scale mechanical characterization shows that collagen gels and degradable synthetic gels display enhanced stress relaxation post-degradation. Stress relaxation is then tuned by systematically varying degradability, resulting in the regulation of cell spreading. This identifies degradability as a key chemomechanical design feature. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=181 SRC="FIGDIR/small/605514v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@13a701dorg.highwire.dtl.DTLVardef@196bb05org.highwire.dtl.DTLVardef@d04613org.highwire.dtl.DTLVardef@1a8b1d1_HPS_FORMAT_FIGEXP M_FIG C_FIG