Mechanochemical Switches in the Regulation of Protein Functional States

A large number of cell-life fundamental processes are regulated by mechanical tensions. The main pathway along which these mechanical tensions are transmitted is the physical connection between the cytoskeleton and the extracellular matrix (ECM). The same mechanical tensions trigger signalling pathways by switching-on new functionalities in the stressed biomolecules. Recently, also the cleavage or formation of disulfide bonds have been proposed to be able to trigger biochemical signals. Until a few years ago these bonds were thought to be selected by evolution to serve two main purposes: to stabilize the native conformation of a protein by entropically destabilizing the unfolded form and to help maintaining protein integrity in a chemically and mechanically harsh extracellular environment. This point of view was therefore looking at disulfide bonds just as simple inert structural features. This point of view is now considered too limited. The disulfide bond is in fact an intrinsically labile bond that can be reversibly cleaved and reformed with the help of various physiological agents. It can therefore act as a reversible switch that can turn off and on biochemical signals. We analyze the possibility that these two switching mechanisms might act synergically in concert. These biological switching mechanisms can be a source of inspiration for the tailoring and the construction of nanodevices.