How deeply cells feel?

Cellular organization within a multicellular organism requires that a cell assess its relative location, taking in multiple cues from its microenvironment. Given that the extracellular matrix (ECM) consists of the most abundant proteins in animals and contributes both structure and elasticity to tissues, ECM probably provides key physical cues to cells. In vivo, in the vicinity of many tissue cell types, fibrous characteristics of the ECM are less discernible than the measurably distinct elasticity that characterizes different tissue microenvironments. As a cell engages matrix and actively probes, it senses the local elastic resistance of the ECM and nearby cells via their deformation, and - similar to the proverbial princess who feels a pea placed many mattresses below - the cell seems to possess feedback and recognition mechanisms that establish how far it can feel. Here, by utilizing polyacrylamide hydrogels with various thickness, we showed that cells increasingly respond to the rigidity of an underlying 'hidden' surface starting at about 10-20 μm gel thickness with a characteristic tactile length of less than about 5 μm.