Newswise — Objects have a fascinating ability to enhance their longevity through self-sacrifice. This can be observed in various ways, such as the use of dummy burial chambers to deceive tomb raiders, the melting of a fuse in an electrical circuit to protect appliances, or a lizard shedding its tail to ensure its escape. Similarly, within collagen, the most abundant protein in our bodies, sacrificial parts play a significant role. Scientists at the Heidelberg Institute for Theoretical Studies (HITS) have recently shed light on how the rupture of weak sacrificial bonds within collagen tissue aids in localizing damage caused by excessive force, minimizing adverse effects on surrounding tissue, and facilitating recovery. These findings, published in Nature Communications, provide crucial insights into collagen's rupture mechanisms, offering a deeper understanding of tissue degradation, material aging, and potential advancements in tissue engineering techniques.
Lead researcher Frauke Gräter from HITS explains, "Collagen's remarkable crosslink chemistry appears to be perfectly adapted to handle mechanical stress. By utilizing a combination of computational and experimental approaches to investigate collagen in rat tissue, our study suggests that weak bonds within collagen's crosslinks have a higher tendency to rupture compared to other bonds, such as those within the collagen backbone. This serves as a protective mechanism, enabling the localization of harmful chemical and physical effects resulting from ruptures, while likely supporting molecular recovery processes."
Collagen makes up approximately 30 percent of all proteins in the human body, fulfilling various essential functions. It imparts strength to bones, elasticity to skin, safeguards organs, provides flexibility to tendons, assists in blood clotting, and supports the growth of new cells. Structurally, collagen resembles a triple-braided helix, with three chains of amino acids intertwining to form a robust and rigid backbone. Each collagen fiber consists of numerous individual molecules staggered and interconnected through crosslinks, contributing to collagen's mechanical stability. While it was previously understood that collagen crosslinks are susceptible to rupture, little was known about the specific rupture sites or the reasons behind their occurrence.
The Molecular Biomechanics Group at HITS embarked on a quest to unravel these mysteries by employing computer simulations to study collagen at various biological scales and under different mechanical forces. To validate their findings, they conducted gel electrophoresis and mass spectrometry experiments on rat tails, flexors, and Achilles tendons. Through rigorous testing, the team identified specific points of breakage in collagen and observed how mechanical forces propagate through the tissue's intricate hierarchical structure, bearing the load on its chemical bonds.
In mature collagen crosslinks, there exist two arms, with one arm being weaker compared to other bonds in collagen tissue. When subjected to excessive force, the weaker arm tends to rupture first, dissipating the force and confining detrimental effects to localized areas. The scientists discovered that in regions where weak bonds exist within collagen tissue, 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.
Previous research conducted by HITS scientists had revealed that excessive mechanical stress on collagen generates radicals, leading to damage and oxidative stress within the body. Benedikt Rennekamp, the study's first author, explains, "Our latest research demonstrates the vital role of sacrificial bonds in collagen in maintaining the overall integrity of the material and localizing the impact of mechanical stress that could otherwise have catastrophic consequences for the tissue. As collagen is a major constituent of our body's tissues, uncovering and understanding these rupture sites provide valuable insights into collagen mechanics and opens up possibilities for developing strategies to enhance its resilience and mitigate damage."
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