Guangdong Provincial Engineering Research Center of Molecular Imaging, Department of Radiology, Cardiac Surgery and Structural Heart Disease Unit of Cardiovascular Center, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519000, China.
Department of Biomedical Engineering, Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, Utah 84112, United States.
J Am Chem Soc. 2023 May 24;145(20):10901-10916. doi: 10.1021/jacs.3c00713. Epub 2023 May 9.
Collagen provides mechanical and biological support for virtually all human tissues in the extracellular matrix (ECM). Its defining molecular structure, the triple-helix, could be damaged and denatured in disease and injuries. To probe collagen damage, the concept of collagen hybridization has been proposed, revised, and validated through a series of investigations reported as early as 1973: a collagen-mimicking peptide strand may form a hybrid triple-helix with the denatured chains of natural collagen but not the intact triple-helical collagen proteins, enabling assessment of proteolytic degradation or mechanical disruption to collagen within a tissue-of-interest. Here we describe the concept and development of collagen hybridization, summarize the decades of chemical investigations on rules underlying the collagen triple-helix folding, and discuss the growing biomedical evidence on collagen denaturation as a previously overlooked ECM signature for an array of conditions involving pathological tissue remodeling and mechanical injuries. Finally, we propose a series of emerging questions regarding the chemical and biological nature of collagen denaturation and highlight the diagnostic and therapeutic opportunities from its targeting.
胶原蛋白为细胞外基质（ECM）中的几乎所有人类组织提供机械和生物学支持。其特有的分子结构，三螺旋，可以在疾病和损伤中受损和变性。为了探测胶原蛋白的损伤，胶原蛋白杂交的概念已经被提出、修订和验证，通过一系列早在 1973 年就有报道的研究：胶原蛋白模拟肽链可以与天然胶原蛋白变性链形成杂交三螺旋，但不能与完整的三螺旋胶原蛋白蛋白形成杂交三螺旋，从而能够评估组织中胶原蛋白的蛋白水解降解或机械破坏。在这里，我们描述了胶原蛋白杂交的概念和发展，总结了几十年来关于胶原蛋白三螺旋折叠规律的化学研究，并讨论了越来越多的关于胶原蛋白变性的生物医学证据，胶原蛋白变性作为一种以前被忽视的细胞外基质特征，与涉及病理性组织重塑和机械损伤的一系列情况有关。最后，我们提出了一系列关于胶原蛋白变性的化学和生物学性质的新兴问题，并强调了针对该问题的诊断和治疗机会。
