Mechanics of the extracellular matrix (ECM) play a pivotal role in governing cell behavior, such as cell spreading and differentiation. ECM mechanics have been recapitulated primarily in elastic hydrogels, including with dynamic properties to mimic complex behaviors (e.g., fibrosis); however, these dynamic hydrogels fail to introduce the viscoelastic nature of many tissues. Here, we developed a two-step crosslinking strategy to first form (via platinum-catalyzed crosslinking) networks of polydimethylsiloxane (PDMS) and then to increase PDMS crosslinking (via thiol-ene click reaction) in a temporally-controlled manner. This photoinitiated reaction increased the compressive modulus of PDMS up to 10-fold within minutes and was conducted under cytocompatible conditions. With stiffening, cells displayed increased spreading, changing from ∼1300 to 1900 μm² and from ∼2700 to 4600 μm² for fibroblasts and mesenchymal stem cells, respectively. In addition, higher myofibroblast activation (from ∼2 to 20%) for cardiac fibroblasts was observed with increasing PDMS substrate stiffness. These results indicate a cellular response to changes in PDMS substrate mechanics, along with a demonstration of a mechanically dynamic and photoresponsive PDMS substrate platform to model the dynamic behavior of ECM.

中文翻译：

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机械动态PDMS基板可研究不断变化的细胞环境

细胞外基质（ECM）的力学在控制细胞行为（例如细胞扩散和分化）中起着关键作用。主要在弹性水凝胶中概述了ECM机理，包括具有模仿复杂行为（例如纤维化）的动态特性。然而，这些动态水凝胶无法引入许多组织的粘弹性。在这里，我们开发了两步交联策略，首先以时间可控的方式形成（通过铂催化的交联）聚二甲基硅氧烷（PDMS）网络，然后增加PDMS的交联（通过硫醇-烯点击反应）。这种光引发的反应在数分钟内将PDMS的压缩模量提高了10倍，并且是在细胞相容性条件下进行的。随着硬化，细胞显示出增加的扩散，²并从~2700至4600微米²为成纤维细胞和间充质分别干细胞。此外，随着PDMS底物硬度的增加，观察到心脏成纤维细胞的成纤维细胞活化更高（约2％至20％）。这些结果表明细胞对PDMS基板力学变化的反应，以及对机械动态和光响应性PDMS基板平台进行建模以演示ECM动力学行为的演示。