Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, GA 30332, USA.
Proc Natl Acad Sci U S A. 2012 May 8;109(19):7251-6. doi: 10.1073/pnas.1118088109. Epub 2012 Apr 23.
Applied forces and the biophysical nature of the cellular microenvironment play a central role in determining cellular behavior. Specifically, forces due to cell contraction are transmitted into structural ECM proteins and these forces are presumed to activate integrin "switches." The mechanism of such switches is thought to be the partial unfolding of integrin-binding domains within fibronectin (Fn). However, integrin switches remain largely hypothetical due to a dearth of evidence for their existence, and relevance, in vivo. By using phage display in combination with the controlled deposition and extension of Fn fibers, we report the discovery of peptide-based molecular probes capable of selectively discriminating Fn fibers under different strain states. Importantly, we show that the probes are functional in both in vitro and ex vivo tissue contexts. The development of such tools represents a critical step in establishing the relevance of theoretical mechanotransduction events within the cellular microenvironment.
施加的力和细胞微环境的生物物理性质在决定细胞行为方面起着核心作用。具体来说，由于细胞收缩产生的力会传递到结构性细胞外基质（ECM）蛋白上，并且这些力被认为可以激活整合素“开关”。这种开关的机制被认为是纤维连接蛋白（Fn）中整合素结合域的部分展开。然而，由于缺乏整合素开关在体内存在的证据，它们在很大程度上仍然是假设性的。通过使用噬菌体展示技术与纤维连接蛋白纤维的受控沉积和延伸相结合，我们报告了发现基于肽的分子探针，这些探针能够在不同的应变状态下选择性地识别纤维连接蛋白纤维。重要的是，我们表明这些探针在体外和离体组织环境中都是功能有效的。此类工具的开发是在细胞微环境中建立理论力学转导事件相关性的关键步骤。
