Cyclic stretch-regulated wound healing

Abstract

Living cells often experience cyclic stretches in both physiological and pathological conditions, such as those found during wound closure, embryonic development and pulmonary fibrosis. Critical challenges in the field of mechanobiology are understanding whether cells respond to these stimuli via physiological pathways or by pathological pathways, and how to switch back to physiological homeostasis once the latter occurs. A longstanding model for trying to tease this apart is culturing monolayer cells on a stretchable membrane, which simulates these conditions and potentially enables researchers to examine how cells react to cyclic stretch. The results can vary substantially, depending on the cell type, amplitude, duration and frequency of the applied stretch (1, 2). Specifically, a great diversity of cellular responses (1-4) have been reported, including 1) re-alignment of cells, associated with the remodeling of cellular stress fibers and focal adhesions; 2) altered cell proliferation or apoptosis; 3) migration of cells driven by stretch-triggered formation of lamellipodia; 4) secretion of extracellular matrix (ECM) proteins that are critical for tissue remodeling; 5) activation of mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-kB) and Wnt signaling pathways; and 6) upregulation of genes involved in cell adhesion and inflammation.