Hyaluronan Disrupts Cardiomyocyte Organization within 3D Fibrin-Based Hydrogels
Hyaluronan Disrupts Cardiomyocyte Organization within 3D Fibrin-Based Hydrogels
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DOI：
10.1016/j.bpj.2019.02.018
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发表时间：
2019-04-02
影响因子：
3.4
通讯作者：
Janmey, Paul A.
中科院分区：
文献类型：
--
作者：
Bouhrira, Nesrine;Galie, Peter A.;Janmey, Paul A.
体内细胞外基质含有可变但通常大量的影响细胞和组织功能的糖胺聚糖。透明质酸 (HA) 是早期发育期间和心肌梗塞后心肌细胞外基质中丰富的糖胺聚糖。其灵活的阴离子结构对基质内的机械响应和间质液流动有很大影响。此外，HA 通过一系列细胞表面受体（包括 CD44、RHAMM/CD168 和其他表面暴露结构）对细胞产生直接的生化作用。最近的研究表明，HA 调节心肌细胞和其他细胞类型对不同弹性模量的二维基质的反应。本研究在体外研究了不同成分和机械特性的三维基质中心肌细胞和心脏成纤维细胞对 HA 的力响应。 HA 显着降低了张力计测试平台和微型组织测量仪中细胞基质结构所施加的力。然而，其作用与海藻酸盐没有什么不同，海藻酸盐是一种具有相同电荷密度但没有特异性跨膜受体的阴离子多糖。因此，这些结果表明，HA 在三维水凝胶中发挥了通用的物理化学效应，在研究细胞-基质相互作用时必须考虑到这一效应。
The extracellular matrix in vivo contains variable but often large amounts of glycosaminoglycans that influence cell and tissue function. Hyaluronan (HA) is an abundant glycosaminoglycan within the extracellular matrix of the myocardium during early development and in the aftermath of a myocardial infarction. Its flexible anionic structure has a strong influence on mechanical response and interstitial fluid flow within the matrix. Additionally, HA has a direct, biochemical effect on cells through an array of cell-surface receptors, including CD44, RHAMM/CD168, and other surface-exposed structures. Recent studies have shown that HA modulates the response of cardiomyocytes and other cell types to two-dimensional substrates of varying elastic moduli. This study investigates the force response to HA of cardiomyocytes and cardiac fibroblasts within three-dimensional matrices of variable composition and mechanical properties in vitro. HA significantly decreased the force exerted by the cell-matrix constructs in a tensiometer testing platform and within microfabricated tissue gauges. However, its effect was no different from that of alginate, an anionic polysaccharide with the same charge density but no specific transmembrane receptors. Therefore, these results establish that HA exerts a generic physical-chemical effect within three-dimensional hydrogels that must be accounted for when interrogating cell-matrix interactions.