Les liaisons dangereuses: Adhesion molecules do it statistically

In 1970 Jacques Monod—one of the founding fathers of molecular biology—wrote his classic text Le hasard et la nécessité (1), in which he emphasized the fundamentally different role in molecular biology of covalent chemical bonds on the one hand and polar, hydrogen, and van der Waals’ bonding on the other hand. Strong covalent bonds can be broken only by the expenditure of a significant number of ATP fuel molecules and are suitable to hold together the individual atoms of a biological macromolecule, like a protein or DNA. Weaker, noncovalent bonds can be broken by the expenditure of just a single ATP molecule and are more suitable to collectively stabilize the architecture of macromolecules or, since they are easily broken up, to be used by signaling molecules transferring information from one part of the cell to another or from one cell to another.

Can we use this classification also for larger complexes? Adhesion proteins expressed on the surface of a cell play a central role in both providing structural integrity to cells and in transferring information to a cell. For example, the successful establishment of an adhesive link between a cell and a surface by integrins initiates multiple cascades of signaling pathways that can lead to cell motion (2). The nature of the expressed adhesion molecules of a cell also can act as an address of a differentiated cell during the tissue formation of an embryo (3), while endothelial cells lining the gut and blood vessels are stapled together by rivets consisting of clusters of adhesion molecules. Finally, the recognition of “self” from “non-self” during the immune response in part involves “lock-and-key” adhesion between adhesion molecules of the white blood cells of the immune systems with partner adhesion molecules on the target cells (4).

Adhesion molecules rely on noncovalent bonds …