Figure 1

Mechanism of mechanotransduction of stem cells activated by matrix stiffness. The initial tension caused by stress fiber contraction is balanced by the microtubules resisting the resulting compression forces and the traction stress exerted on the extracellular matrix (ECM) across the focal adhesions, which directly cause the resultant force determined by matrix stiffness, contributing to microtubule compression. Then, the cell reads out the resultant forces from traction stress through the activation of integrin-mediated signal transduction pathways, which mediate actin filament polymerization and therefore change stress fiber contractility. Also, the initial tension from stress fiber contraction and the opposing compressive forces exerted by microtubules might also transmit into the nucleus and be resisted by lamin-A, which in turn promotes cell contractility by activating the transcriptional pathway that regulates actin filament bundling. Through cytoskeleton-based feedback loops, a cell changes its maximal mechanosensitivity close to the microtubule compression determined by matrix stiffness. Some transcriptional pathway modulates lamin-A expression, and feedback by lamin-A indirectly regulates transcriptional pathways, which crosstalk with integrin-mediated signaling and ultimately direct stem cell differentiation.