Vascular smooth muscle cell functional contractility depends on extracellular mechanical properties.
Vascular smooth muscle cell functional contractility depends on extracellular mechanical properties.
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DOI：
10.1016/j.jbiomech.2015.07.029
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发表时间：
2015-09-18
影响因子：
2.4
通讯作者：
Alford PW
中科院分区：
文献类型：
--
作者：
Steucke KE;Tracy PV;Hald ES;Hall JL;Alford PW
血管平滑肌细胞的主要功能是通过主动收缩和舒张来维持血管的稳态。在高血压和动脉粥样硬化等疾病中，这种功能受到抑制，同时血管平滑肌细胞周围的机械环境发生变化。众所周知，细胞功能和细胞外力学是相互关联的;底物模量的变化影响细胞迁移、增殖和分化。迄今为止，尚不清楚血管平滑肌细胞的细胞外力学环境如何影响其收缩功能。在这里，我们已经建立在以前的血管肌肉薄膜技术，以开发一种可变模量的血管肌肉薄膜，测量血管组织的功能收缩性与一系列的病理和生理模量的基板。使用这种改性的血管肌肉薄膜，我们发现，血管平滑肌细胞产生更大的应力基板上具有较高的模量相比，基板具有较低的模量。然后，我们测量了通常被认为表明血管平滑肌细胞收缩表型的蛋白质标记物，发现该表型不受底物模量的影响。这些数据表明，血管平滑肌细胞的细胞外环境的机械特性直接影响其功能行为，并且不会诱导表型转换。
Vascular smooth muscle cells’ primary function is to maintain vascular homeostasis through active contraction and relaxation. In diseases such as hypertension and atherosclerosis, this function is inhibited concurrent to changes in the mechanical environment surrounding vascular smooth muscle cells. It is well established that cell function and extracellular mechanics are interconnected; variations in substrate modulus affect cell migration, proliferation, and differentiation. To date, it is unknown how the evolving extracellular mechanical environment of vascular smooth muscle cells affects their contractile function. Here, we have built upon previous vascular muscular thin film technology to develop a variable-modulus vascular muscular thin film that measures vascular tissue functional contractility on substrates with a range of pathological and physiological moduli. Using this modified vascular muscular thin film, we found that vascular smooth muscle cells generated greater stress on substrates with higher moduli compared to substrates with lower moduli. We then measured protein markers typically thought to indicate a contractile phenotype in vascular smooth muscle cells and found that phenotype is unaffected by substrate modulus. These data suggest that mechanical properties of vascular smooth muscle cells’ extracellular environment directly influence their functional behavior and do so without inducing phenotype switching.