School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA.
Department of Biomedical Engineering, Schools of Engineering and Medicine, University of Virginia, Charlottesville, VA, USA.
Nat Commun. 2024 Oct 9;15(1):8751. doi: 10.1038/s41467-024-52742-3.
The extracellular matrix (ECM) is a protein polymer network that physically supports cells within a tissue. It acts as an important physical and biochemical stimulus directing cell behaviors. For fibronectin (Fn), a predominant component of the ECM, these physical and biochemical activities are inextricably linked as physical forces trigger conformational changes that impact its biochemical activity. Here, we analyze whether oxidative post-translational modifications, specifically glutathionylation, alter Fn's mechano-chemical characteristics through stretch-dependent protein modification. ECM post-translational modifications represent a potential for time- or stimulus-dependent changes in ECM structure-function relationships that could persist over time with potentially significant impacts on cell and tissue behaviors. In this study, we show evidence that glutathionylation of Fn ECM fibers is stretch-dependent and alters Fn fiber mechanical properties with implications on the selectivity of engaging integrin receptors. These data demonstrate the existence of multimodal post-translational modification mechanisms within the ECM with high relevance to the microenvironmental regulation of downstream cell behaviors.
细胞外基质（ECM）是一种蛋白质聚合物网络，它为组织内的细胞提供物理支撑。它作为一个重要的物理和生化刺激物，指导着细胞的行为。对于细胞外基质中的主要成分纤维连接蛋白（Fn），这些物理和生化活动是紧密相关的，因为物理力会引发构象变化，从而影响其生化活性。在这里，我们分析了氧化翻译后修饰，特别是谷胱甘肽化，是否通过拉伸依赖性蛋白修饰改变 Fn 的机械化学特性。细胞外基质翻译后修饰代表了细胞外基质结构-功能关系中时间或刺激依赖性变化的可能性，这种变化可能随着时间的推移而持续存在，并对细胞和组织行为产生潜在的重大影响。在这项研究中，我们证明了 Fn 细胞外基质纤维的谷胱甘肽化是拉伸依赖性的，并改变了 Fn 纤维的机械性能，这对整合素受体的结合具有选择性意义。这些数据表明，细胞外基质中存在着多种翻译后修饰机制，与下游细胞行为的微环境调节具有高度相关性。
