Work

Matrix degradation enhances stress relaxation, regulating cell adhesion and spreading

Year: 2025

Type: article

Abstract: In native extracellular matrices (ECM), cells utilize matrix metalloproteinases (MMPs) to degrade and remodel their microenvironment. Accordingly, synthetic matrices have been engineered to permit MMP-mediated cleavage, facilitating cell spreading, migration, and interactions. However, the interplay between matrix degradability and mechanical properties remains underexplored. We hypothesized that MMP activity induces immediate mechanical alterations in the ECM, which are subsequently detected by cells. We observed that both fibrillar collagen and synthetic degradable matrices exhibit enhanced stress relaxation following MMP exposure. Cells responded to these variations in relaxation by modulating their spreading and focal adhesions. Furthermore, we demonstrated that stress relaxation and cell spreading can be precisely controlled through the rational design of matrix degradability. These findings establish a fundamental link between matrix degradability and stress relaxation, with potential implications for a broad spectrum of biological applications.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.2416771122

Authors: Badri Narayanan Narasimhan, Stephanie I. Fraley

Institution: University of California San Diego

Language: English

Topic: Cellular Mechanics and Interactions

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Funders: National Science Foundation, American Cancer Society, National Cancer Institute, National Institute of Neurological Disorders and Stroke

Awards: Regulation of Collective Breast Cancer Invasion and Metastasis, Integrating Four-Dimensional Cell Migration Modeling with Quantitative Experiments, University of California San Diego Neuroscience Microscopy Imaging Core, G986932322