Cells Sense Rigidity of their Micro-Environment by a Unique Force-Sensing Displacement Cassette

Abstract

Eukaryotic cells modulate their gene expression profile and differentiation in response to physical cues in their micro environment. The exact mechanism by which the cells sense the stiffness of the substrate has not yet been completely understood. Recent studies with micropillar arrays indicate that cells move fibronectin pillars for a constant displacement irrespective of the stiffness. Thus, rigidity sensing may involve the integration of the force required. To further understand the mechanism involved, we increased the center-to-center spacing of the micropillars to 3 micrometers and compared two different cell lines. We observed that the displacements of the pillars were constant over an order of magnitude variation in stiffness of pillars and a six-fold variation in spacing; however, the mouse embryonic fibroblast (RPTPα+/+) and cells foreskin fibroblast (HFF) cells exerted consistent peak pillar displacements of ∼70nm and ∼120nm respectively. Chemical and genetic perturbations of likely components of the mechanosensing machinery are being used to probe its composition and working. Delineating the components of this cassette is crucial to understand the sensing of the substrate stiffness by cells with implications for cell differentiation and metastasis.