The fibrous character of pericellular matrix mediates cell mechanotransduction

Abstract

Cells in solid tissues sense and respond to mechanical signals that are transmitted through extracellular matrix (ECM) over distances that are many times their size. This long-range force transmission is known to arise from strain-stiffening and buckling in the collagen fiber ECM network, but must also pass through the denser pericellular matrix (PCM) that cells form by secreting and compacting nearby collagen. However, the role of the PCM in the transmission of mechanical signals is still unclear. We therefore studied an idealized computational model of cells embedded within fibrous collagen ECM and PCM. Our results suggest that the smaller network pore sizes associated with PCM attenuates tension-driven collagen-fiber alignment, undermining long-range force transmission and shielding cells from mechanical stress. However, elongation of the cell body or anisotropic cell contraction can compensate for these effects to enable long distance force transmission. Results are consistent with recent experiments that highlight an effect of PCM on shielding cells from high stresses. Results have implications for the transmission of mechanical signaling in development, wound healing, and fibrosis.