Arterial Extracellular Matrix: A Mechanobiological Study of the Contributions and Interactions of Elastin and Collagen
Arterial Extracellular Matrix: A Mechanobiological Study of the Contributions and Interactions of Elastin and Collagen
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DOI：
10.1016/j.bpj.2014.05.014
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发表时间：
2014-06-17
影响因子：
3.4
通讯作者：
Zhang, Yanhang
中科院分区：
文献类型：
--
作者：
Chow, Ming-Jay;Turcotte, Raphael;Zhang, Yanhang
弹性蛋白和胶原细胞外基质(ECM)的复杂网络结构构成了动脉壁的主要承重成分。弹性蛋白和胶原蛋白之间的结构和力学生物相互作用对于正常运作的动脉是重要的。在这里，我们通过机械加载和多光子成像相结合的方法研究了弹性蛋白和胶原的组织、重排和募集。用多光子视频率显微镜进行双光子激发荧光和二次谐波产生方法，实时捕捉双轴变形过程中弹性蛋白和胶原结构的变化。用酶法去除弹性蛋白，以评估剩余胶原结构的结构变化。利用二维快速傅立叶变换和分形分析相结合的方法对弹性蛋白和胶原的结构变化进行了定量分析，从而可以更全面地了解结构变化。我们的研究提供了新的定量证据，据我们所知，不同动脉ECM组件在机械负荷下的顺序接合。外膜胶原以大的波状纤维束的形式存在，在20%的应变后表现出纤维结合。中层胶原蛋白在整个拉伸过程中都处于接合状态，并观察到高达20%应变的显著弹性纤维接合，之后接合平台处于停滞状态。纤维取向分布函数在机械载荷作用下，ECM结构的变化明显不同。中层胶原呈明显的周向分布，而外膜胶原纤维族在无或低机械应变时被波浪形所遮挡。两层中的胶原纤维在不均匀的双轴载荷下表现出明显的重排。弹性纤维的分布要均匀得多，并且由于加载而保持相对不变。去除弹性蛋白会产生与机械负荷类似的胶原蛋白结构变化。我们的研究表明，弹性纤维处于拉伸状态，并向胶原蛋白施加内在的压应力。
The complex network structure of elastin and collagen extracellular matrix (ECM) forms the primary load bearing components in the arterial wall. The structural and mechanobiological interactions between elastin and collagen are important for properly functioning arteries. Here, we examined the elastin and collagen organization, realignment, and recruitment by coupling mechanical loading and multiphoton imaging. Two-photon excitation fluorescence and second harmonic generation methods were performed with a multiphoton video-rate microscope to capture real time changes to the elastin and collagen structure during biaxial deformation. Enzymatic removal of elastin was performed to assess the structural changes of the remaining collagen structure. Quantitative analysis of the structural changes to elastin and collagen was made using a combination of two-dimensional fast Fourier transform and fractal analysis, which allows for a more complete understanding of structural changes. Our study provides new quantitative evidence, to our knowledge on the sequential engagement of different arterial ECM components in response to mechanical loading. The adventitial collagen exists as large wavy bundles of fibers that exhibit fiber engagement after 20% strain. The medial collagen is engaged throughout the stretching process, and prominent elastic fiber engagement is observed up to 20% strain after which the engagement plateaus. The fiber orientation distribution functions show remarkably different changes in the ECM structure in response to mechanical loading. The medial collagen shows an evident preferred circumferential distribution, however the fiber families of adventitial collagen are obscured by their waviness at no or low mechanical strains. Collagen fibers in both layers exhibit significant realignment in response to unequal biaxial loading. The elastic fibers are much more uniformly distributed and remained relatively unchanged due to loading. Removal of elastin produces similar structural changes in collagen as mechanical loading. Our study suggests that the elastic fibers are under tension and impart an intrinsic compressive stress on the collagen.