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The Molecular Mechanics of Collagen Degradation: Implications for Human Disease

Abstract

Collagen is a unique structural protein that imparts tensile strength to bone, tendons, and numerous other tissues. Like many biological polymers, collagen is continually synthesized and degraded in the extracellular space. While collagen degradation is a normal part of collagen homeostasis, excessive collagenolysis has been implicated in a number of human diseases such as arthritis, cancer, and atherosclerosis. In this work we demonstrate how molecular simulations can be used to study the mechanics of collagen degradation. Dynamical simulations, which model the structural fluctuations that collagen can undergo under physiologic conditions, reveal that portions of collagen are quite flexible—a somewhat counterintuitive finding. Moreover, this flexibility likely facilitates the recognition and cleavage of collagen by proteolytic enzymes. Experiments on collagen-like model compounds are consistent with these observations and demonstrate that new insights into the physical basis of collagenolysis can be obtained from a combination of experiment and computation. More importantly, these results highlight new avenues for the development of potential therapies for disorders that involve abnormal collagen catabolism.

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Correspondence to C. M. Stultz.

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Salsas-Escat, R., Stultz, C.M. The Molecular Mechanics of Collagen Degradation: Implications for Human Disease. Exp Mech 49, 65–77 (2009). https://doi.org/10.1007/s11340-007-9105-1

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  • DOI: https://doi.org/10.1007/s11340-007-9105-1

Keywords

  • Collagen
  • Collagenolysis
  • Molecular simulations
  • Protein dynamics
  • Protein structure