Department of Bioengineering, University of Utah, Salt Lake City, Utah 84112, USA.
Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, Utah 84112, USA.
Nat Commun. 2017 Mar 22;8:14913. doi: 10.1038/ncomms14913.
Mechanical injury to connective tissue causes changes in collagen structure and material behaviour, but the role and mechanisms of molecular damage have not been established. In the case of mechanical subfailure damage, no apparent macroscale damage can be detected, yet this damage initiates and potentiates in pathological processes. Here, we utilize collagen hybridizing peptide (CHP), which binds unfolded collagen by triple helix formation, to detect molecular level subfailure damage to collagen in mechanically stretched rat tail tendon fascicle. Our results directly reveal that collagen triple helix unfolding occurs during tensile loading of collagenous tissues and thus is an important damage mechanism. Steered molecular dynamics simulations suggest that a likely mechanism for triple helix unfolding is intermolecular shearing of collagen α-chains. Our results elucidate a probable molecular failure mechanism associated with subfailure injuries, and demonstrate the potential of CHP targeting for diagnosis, treatment and monitoring of tissue disease and injury.
机械性损伤会导致结缔组织中的胶原蛋白结构和材料性能发生变化，但分子损伤的作用和机制尚未确定。在机械性亚失效损伤的情况下，虽然无法检测到明显的宏观损伤，但这种损伤会引发并加剧病理过程。在这里，我们利用胶原杂交肽（CHP），它通过三螺旋形成与展开的胶原蛋白结合，来检测机械拉伸的大鼠尾腱束中胶原蛋白的分子水平亚失效损伤。我们的结果直接表明，在胶原组织的拉伸加载过程中会发生胶原蛋白三螺旋展开，因此这是一种重要的损伤机制。定向分子动力学模拟表明，三螺旋展开的一种可能机制是胶原蛋白α-链的分子间剪切。我们的结果阐明了与亚失效损伤相关的可能分子失效机制，并表明 CHP 靶向在组织疾病和损伤的诊断、治疗和监测方面具有潜力。
