Physical basis of Cell-Matrix Adhesions and Growth Through High Forces
Cells adhere to matrices through 100 nm clusters of integrins and grow dependent upon matrix rigidity. Similar integrin clusters of 50 integrins in 100 nm circles form on lipid bilayers and glass, raising the question of whether they form on small matrix fibers <20nm. Using 10nm lines coated with fibronectin ligand, we find that single lines will not but two lines separated by 80 nm will support 100nm clusters. We suggest that clusters contain many unliganded but activated integrins. Clusters are contracted by sarcomeric units to determine matrix rigidity. Contractions of ~120nm totally generate forces of >3000pN that stimulate adhesion assembly and growth (Meacci et al., 2016; Wolfenson et al., 2016). In dual stiffness pillar experiments, we find that very rigid (60 pN/nm) pillars are pulled to 60 nm by 110-150 myosin heads in bipolar filaments (>20 pN/head), which is theoretically possible because of the slow velocity (2-3 nm/sec) of the contractions (Lohner, Ruprecht, Prost and Sheetz). On soft surfaces, rigidity-sensing causes apoptosis but the depletion of tropomyosin 2.1, a-actinin, or myosin IIA will block rigidity-sensing (Meacci et al., 2016; Saxena et al., 2017b; Wolfenson et al., 2016) causing transformed growth. All transformed cancer cells tested lacked rigidity sensing (Yang et al., submitted) and the restoration of normal levels of cytoskeletal proteins enabled rigidity sensing and rigidity-dependent growth or anoikis. Thus, depletion of rigidity sensors results in transformed growth of cancer cells. In the rigidity sensors, non-muscle myosin heads can develop much higher forces than measured in vitro (>40 pN/myosin head)..
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