The magnitudes of those forces vary among different cell and tissue types, as do cells’ sensitivities to changes in magnitudes, frequencies, and durations of the forces.
Using Arg-Gly-Asp peptide-coated magnetic beads that clustered integrins and induced the formation of focal adhesions beneath the beads on the inner surface of the cell membrane, I applied measured amounts of stress to the surfaces of living cells and found that cell stiffness increased with the magnitude of the forces.
Subsequently, using a laser tweezer, Mike Sheetz’s lab at Columbia University independently confirmed that focal adhesions transmit external forces into the cell.2 In addition, two other groups-those of Yu-Li Wang, now at Carnegie Mellon University, and Benny Geiger at the Weizmann Institute of Science-found that focal adhesions also transmit forces generated inside the cell by powerful molecular motors such as myosin II, which binds to F-actin in the cytoskeleton, out into the ECM. This research showed that focal adhesion-mediated transmission of mechanical signals is bidirectional.
Using a micropipette coated with fibronectin to attach to the cell surface, the researchers pulled on the cell and found that the nuclear envelope distorted.
Because endogenous forces are constantly generated inside a living cell, these findings suggest that gene expression might be incessantly regulated by physical forces via this direct structural pathway and the indirect pathways of matrix rigidity-dependent nuclear translocation of certain factors, such as yes-associated protein and TWIST1.
The role of physical forces in biology is by no means limited to stem cells and cancer biology.
“Matrix elasticity directs stem cell lineage specification,” Cell, 126:677-89, 2006.