Mechanically Enhanced Proline Ring-Opening in Proteins

Proteins such as collagen and elastin are subjected to highly repetitive stresses in the cardiovascular system. These proteins can have half-lives of many decades and, therefore, experience many tens or hundreds of millions of stress-strain cycles. Such a large number of cycles, even for a modest level of stress, subjects these molecules bond breaking and fatigue failure. To gain further insight into bond breaking in mechanically stressed proteins, the mechanical strength of bonds in the polypeptide backbone are estimated using bond dissociation energies from model compounds for individual amino acids. This analysis shows that the N-Cα bond in proline has a bond dissociation energy that is ~60 kJ/mol less than the next weakest bond in a polypeptide backbone. Thus, when mechanically stressed, the pyrrolidine ring of proline will open before other backbone bonds break. Such mechanically enhanced proline ring-opening would maintain structural continuity of the peptide backbone while increasing the length of the backbone by ~0.3 nm per ring-opening. The increase in length would redistribute forces to nearby molecules, thus effectively remodeling the mechanical properties of the tissue involved.