Sacrificial bonds have been found within collagen. These break more rapidly than the foundational structure protecting the overall tissue.
Recent discoveries surrounding collagen, the body’s most abundant protein, have unveiled that sacrificial bonds within it break more rapidly than the foundational structure. This, in turn, safeguards the overall tissue, as harmful radicals produced during mechanical stress are neutralized.
Increasing longevity through unconventional means involves objects sacrificing a portion of themselves. This practice extends from the deployment of decoy burial chambers to confound grave robbers, the deliberate melting of a fuse within an electrical circuit to safeguard other appliances, to the detachment of a lizard’s tail in aid of its escape.
The same principle of sacrificial elements is evident in collagen, the body’s most abundant protein. A recent study conducted by researchers at the Heidelberg Institute for Theoretical Studies (HITS) has unveiled how the breaking of fragile sacrificial bonds within collagen tissue contributes to the localization of damage resulting from excessive force, minimizes adverse effects on the surrounding tissue, and supports the healing process.
Published in Nature Communications, light is shed on the mechanisms of collagen’s rupture, a critical aspect in comprehending tissue deterioration, material aging, and the potential advancement of techniques in tissue engineering.
Frauke Gräter, who spearheaded the research at HITS, comments on collagen’s remarkable crosslink chemistry. The findings, derived from the study of collagen in rat tissue using complementary computational and experimental methods, suggest that the bonds within collagen’s crosslinks, particularly the weaker ones, exhibit a strong propensity to rupture ahead of other bonds, including those in collagen’s backbone. This phenomenon serves as a protective mechanism, confining the harmful chemical and physical consequences of ruptures and likely supporting molecular recovery processes.
Roughly 30 percent of all proteins in the human body are composed of collagen.
It imparts strength to bones, elasticity to skin, protection to organs, flexibility to tendons, contributes to blood clotting, and supports the growth of new cells. Structurally, collagen takes on the appearance of a triple-braided helix, where three chains of amino acids intertwine, forming a sturdy and inflexible backbone.
Within each collagen fiber, numerous individual molecules are staggered and interconnected by crosslinks, enhancing collagen’s mechanical stability. Although it was previously believed that collagen crosslinks were susceptible to rupture, little was known about the specific locations of these bond breakages or the reasons behind their occurrence.
A group of scientists from the Molecular Biomechanics Group at HITS endeavored to unravel these mysteries by employing computer simulations to study collagen at various biological scales and under different mechanical forces. They verified their findings by conducting gel electrophoresis and mass spectrometry experiments on the tails, flexors, and Achilles’ tendons of rats. Through rigorous testing of collagen, specific points of breakage were identified. They observed how force dissipates through the intricate hierarchical structure of the tissue and how its chemical bonds bear the load.
The mature crosslinks within collagen consist of two arms, with one of them being weaker than other bonds within the collagen tissue. When subjected to excessive force, the weaker arm typically gives way first, dispersing the force and confining adverse effects to a localized area. The scientists noted that in regions of collagen tissue where these weak bonds are present, other bonds, both in the crosslinks and the collagen backbone, are more likely to remain intact, thereby preserving the structural integrity of the collagen tissue.
In previous research conducted by scientists at HITS, it was demonstrated that the application of excessive mechanical stress to collagen results in the generation of radicals, leading to damage and oxidative stress within the body.
The most recent study, with Benedikt Rennekamp as the first author, indicates that sacrificial bonds within collagen play a crucial role in preserving the overall material integrity and can assist in confining the effects of this mechanical stress, which might otherwise have disastrous consequences for the tissue. Collagen, being a significant component of bodily tissues, holds great importance. By uncovering and comprehending these rupture sites, valuable insights into collagen mechanics can be obtained, potentially paving the way for the development of strategies to bolster its resilience and mitigate damage.
Collagen is a force-bearing, hierarchical structural protein important to all connective tissue. In tendon collagen, high load even below macroscopic failure level creates mechanoradicals by homolytic bond scission, similar to polymers. The location and type of initial rupture sites critically decide on both the mechanical and chemical impact of these micro-ruptures on the tissue, but are yet to be explored. We here use scale-bridging simulations supported by gel electrophoresis and mass spectrometry to determine breakage points in collagen. We find collagen crosslinks, as opposed to the backbone, to harbor the weakest bonds, with one particular bond in trivalent crosslinks as the most dominant rupture site. We identify this bond as sacrificial, rupturing prior to other bonds while maintaining the material’s integrity. Also, collagen’s weak bonds funnel ruptures such that the potentially harmful mechanoradicals are readily stabilized. Our results suggest this unique failure mode of collagen to be tailored towards combatting an early onset of macroscopic failure and material ageing.