Critical role of cytoskeletal prestress in cellular stiffening

In his recent comment, Isabey discussed the issue of external stress/strain induced cellular stiffening. While the mechanism of this behavior is not fully understood and deserves further investigation, I would like to mention the cellular stiffening (increase of shear stiffness) that depends on the level of the endogenous contractile prestress (pre-tension) generated by myosin II-actin interactions. Earlier experimental evidence for prestress-dependent cellular stiffening in living cells was demonstrated by us and our collaborators (R Hubmayr et al, 96, J Pourati et al, 98, S Cai et al, 98). A more definitive evidence came later in a couple of papers (N Wang et al, PNAS, 2001, N Wang et al, AJP Cell Physiol, 2002) in which we quantified contractile prestress and cell stiffness independently and found strong dependence of cell stiffness on prestress. This result was observed for the same cell spreading area, thus minimizing other potential confounding fators as possible underlying mechanisms. D Discher group later showed similar results in different cell types using different experimental approaches. It is interesting to note that D Weitz group showed prestress-dependent stiffening in actin polymers and that a recent paper from F MaKintosh group (Science Jan 07) showed that it is the tension in the actin polymers and not the crosslinks that is the key to myosin contractile tension induced stiffening of actin polymers. This elegant work pushes the understanding of prestress-dependent stiffening to the molecular level. I propose that many other vital cellular functions could also be dependent on the level of the contractile prestress in living cells, in addition to what we already know now: cell spreading, proliferation and apoptosis (see work of D Ingber lab and C Chen lab), stress propagation and mechanical signaling (our papers).