Optical metrics of the extracellular matrix predict compositional and mechanical changes after myocardial infarction.
Optical metrics of the extracellular matrix predict compositional and mechanical changes after myocardial infarction.
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DOI：
10.1038/srep35823
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发表时间：
2016-11-07
影响因子：
4.6
通讯作者：
Black LD
中科院分区：
文献类型：
--
作者：
Quinn KP;Sullivan KE;Liu Z;Ballard Z;Siokatas C;Georgakoudi I;Black LD
理解细胞外基质（ECM）的组织和力学功能对于制定调节疾病或损伤后伤口愈合的治疗策略至关重要。然而，在心肌梗死（MI）后的重塑过程中，由于细胞数量的快速变化以及无法无损地表征ECM的微观结构和功能，这些关系难以阐明。在这项研究中，我们通过全器官脱细胞处理和非线性光学显微镜直接关联心肌ECM的微观结构和力学性能，从而克服了这些挑战。我们利用二次谐波产生（SHG）和双光子激发自发荧光对脱细胞的健康和梗死心肌内的胶原蛋白组织、含量和交联进行无损量化。拉伸力学测试和成分分析表明，每个图像体积内的累积SHG强度以及平均胶原蛋白自发荧光分别与ECM的胶原蛋白含量和弹性模量显著相关。与健康的ECM相比，梗死组织的胶原蛋白含量和纤维排列显著增加，而交联和弹性模量降低。这些发现表明，交联在梗死后胶原蛋白纤维水平的刚度中起关键作用，并强调了这种无损评估重塑的方法可如何用于理解ECM的结构 - 功能关系。
Understanding the organization and mechanical function of the extracellular matrix (ECM) is critical for the development of therapeutic strategies that regulate wound healing following disease or injury. However, these relationships are challenging to elucidate during remodeling following myocardial infarction (MI) due to rapid changes in cellularity and an inability to characterize both ECM microstructure and function non-destructively. In this study, we overcome those challenges through whole organ decellularization and non-linear optical microscopy to directly relate the microstructure and mechanical properties of myocardial ECM. We non-destructively quantify collagen organization, content, and cross-linking within decellularized healthy and infarcted myocardium using second harmonic generation (SHG) and two photon excited autofluorescence. Tensile mechanical testing and compositional analysis reveal that the cumulative SHG intensity within each image volume and the average collagen autofluorescence are significantly correlated with collagen content and elastic modulus of the ECM, respectively. Compared to healthy ECM, infarcted tissues demonstrate a significant increase in collagen content and fiber alignment, and a decrease in cross-linking and elastic modulus. These findings indicate that cross-linking plays a key role in stiffness at the collagen fiber level following infarction, and highlight how this non-destructive approach to assessing remodeling can be used to understand ECM structure-function relationships.
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影响因子：
3.2
作者：
Amenta, PS;Scivoletti, NA;Myers, JC
通讯作者：
Myers, JC
影响因子：
3.6
作者：
Brown, RM;Millard, AC;Campagnola, PJ
通讯作者：
Campagnola, PJ
影响因子：
16.6
作者：
Evans, Mark A.;Smart, Nicola;Dube, Karina N.;Bollini, Sveva;Clark, James E.;Evans, Hayley G.;Taams, Leonie S.;Richardson, Rebecca;Levesque, Mathieu;Martin, Paul;Mills, Kevin;Riegler, Johannes;Price, Anthony N.;Lythgoe, Mark F.;Riley, Paul R.
通讯作者：
Riley, Paul R.
DOI：
10.1016/j.jmbbm.2014.07.016
发表时间：
2014-11
影响因子：
3.9
作者：
D'Amore, Antonio;Amoroso, Nicholas;Gottardi, Riccardo;Hobson, Christopher;Carruthers, Christopher;Watkins, Simon;Wagner, William R.;Sacks, Michael S.
通讯作者：
Sacks, Michael S.
影响因子：
2.4
作者：
LaComb, Ronald;Nadiarnykh, Oleg;Campagnola, Paul J.
通讯作者：
Campagnola, Paul J.