Department of Mechanical Engineering, University of Utah, Salt Lake City, UT 84112, United States.
Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, United States.
Acta Biomater. 2018 Feb;67:307-318. doi: 10.1016/j.actbio.2017.11.052. Epub 2017 Dec 8.
It is well established that overstretch of arteries alters their mechanics and compromises their function. However, the underlying structural mechanisms behind these changes are poorly understood. Utilizing a recently developed collagen hybridizing peptide (CHP), we demonstrate that a single mechanical overstretch of an artery produces molecular-level unfolding of collagen. In addition, imaging and quantification of CHP binding revealed that overstretch produces damage (unfolding) among fibers aligned with the direction of loading, that damage increases with overstretch severity, and that the onset of this damage is closely associated with tissue yielding. These findings held true for both axial and circumferential loading directions. Our results are the first to identify stretch-induced molecular damage to collagen in blood vessels. Furthermore, our approach is advantageous over existing methods of collagen damage detection as it is non-destructive, readily visualized, and objectively quantified. This work opens the door to revealing additional structure-function relationships in arteries. We anticipate that this approach can be used to better understand arterial damage in clinically relevant settings such as angioplasty and vascular trauma. Furthermore, CHP can be a tool for the development of microstructurally-based constitutive models and experimentally validated computational models of arterial damage and damage propagation across physical scales.
Arteries play a critical role by carrying oxygen and essential nutrients throughout the body. However, trauma to the head and neck, as well as surgical interventions, can overstretch arteries and alter their mechanics. In order to better understand the cause of these changes, we employ a novel collagen hybridizing peptide (CHP) to study collagen damage in overstretched arteries. Our approach is unique in that we go beyond the fiber- and fibril-level and characterize molecular-level disruption. In addition, we image and quantify fluorescently-labeled CHP to reveal a new structure-property relationship in arterial damage. We anticipate that our approach can be used to better understand arterial damage in clinically relevant settings such as angioplasty and vascular trauma.
众所周知，动脉过度拉伸会改变其力学特性并损害其功能。然而，这些变化背后的潜在结构机制还知之甚少。利用最近开发的胶原杂交肽（CHP），我们证明动脉的单次机械过度拉伸会导致胶原的分子水平展开。此外，对 CHP 结合的成像和定量分析表明，过度拉伸会导致与加载方向一致的纤维产生损伤（展开），损伤随过度拉伸的严重程度而增加，并且这种损伤的发生与组织屈服密切相关。这些发现对于轴向和周向加载方向都成立。我们的结果首次确定了血管中胶原拉伸诱导的分子损伤。此外，与现有的胶原损伤检测方法相比，我们的方法具有优势，因为它是非破坏性的，易于可视化并且可以客观地定量。这项工作为揭示动脉中的结构-功能关系开辟了道路。我们预计，这种方法可以用于更好地理解临床相关环境中的动脉损伤，例如血管成形术和血管创伤。此外，CHP 可以成为用于开发基于微观结构的动脉损伤和损伤传播的本构模型以及经过实验验证的计算模型的工具，跨越物理尺度。
动脉通过在全身输送氧气和必需的营养物质发挥着至关重要的作用。然而，头部和颈部的创伤以及手术干预都可能会过度拉伸动脉并改变其力学特性。为了更好地了解这些变化的原因，我们采用了一种新型的胶原杂交肽（CHP）来研究过度拉伸的动脉中的胶原损伤。我们的方法是独特的，因为我们超越了纤维和原纤维水平，并且表征了分子水平的破坏。此外，我们通过成像和定量分析荧光标记的 CHP 来揭示动脉损伤中的新结构-性能关系。我们预计，我们的方法可以用于更好地理解临床相关环境中的动脉损伤，例如血管成形术和血管创伤。
