By studying with the single molecule force spectroscopy (SMFS) methodology the mechanical behaviour of single biomolecules, we are learning how mechanical forces like those present in the extracellular space modify the conformation of proteins, possibly leading to functional switches. We also understand that the functional efficiency of those mechanical switches can rely on their coupling to some independent biochemical control of the protein conformational changes. The disulfide bonds have been recently proposed to act as potential redox switches, even if their structural bases are unclear. Here we discuss, also on the basis of experimental evidences based on SMFS, the possibility that disulfide bond switching and mechanical deformation of extracellular proteins can be coupled, thus leading to an efficient and highly tuned switch for protein function. We propose this as one of the biological mechanisms that regulate extracellular protein functionality. (c) 2006 Elsevier Ltd. All rights reserved.