598461.fig.002
Figure 2: Hypothetical mechanism for earlier cellular responses to changes in mechanical conditions. The principal difference between stretch and compression is characterized by the dissociation of different molecules from the cortical cytoskeleton, for example, alpha-actinin-1 at stretching and alpha-actinin-4 at compression. Under cell stretch, there are cortical cytoskeleton deformations and subsequent shifts in actin filaments relative to each other in the stress fibres. This increases the probability of dissociation of the proteins that connect actin filaments, for example, alpha-actinin-1. Under cell compression, this happens predominantly via membrane deformation so that the conformation of the alpha-actinin-4 binding sites (e.g., due to cholesterol raft convergence) can change. This will lead to a release of proteins which connect with the membrane, for example, alpha-actinin-4. The release of alpha-actinin-4 causes the activation of the expression of the alpha-actinin-1 gene and repression of own expression. This occurs similarly for alpha-actinin-1. The release of different proteins causes activation of different pathways and formation of the response to the increase or decrease in mechanical load. The proposed mechanism is only hypothetical and therefore needs to be checked experimentally.