Department of Physics, University of Ottawa, Ottawa, ON, Canada.
Med Biol Eng Comput. 2010 Oct;48(10):1015-22. doi: 10.1007/s11517-010-0640-z. Epub 2010 Jun 10.
Apoptosis is a critical physiological pathway required for the normal functioning, homeostasis, and development of many organisms. This process is highly regulated at the biochemical level and has been intensively studied. Recent evidence has demonstrated that apoptosis is also a controlled nanomechanical process which relies on feedback between biochemical signaling and the nanomechanical properties of the microenvironment. Deregulation of the nanomechanical breakdown of apoptotic cells results in the poorly timed release of cells and cell debris that leads to the pathogenesis of several inflammatory diseases. In this study, we investigate the nanomechanical consequences of early apoptosis in human fibroblasts grown as single cells and as cell monolayers. These fibroblasts are found within the body and are involved in many processes including wound healing and repair in which apoptosis plays a major role. We find that although the cells undergo massive morphological remodeling and nanomechanical breakdown, the extra-cellular matrix (ECM) acts to maintain monolayer integrity. Via strong interactions between fibronectin and F-actin (fibronexus junctions), the ECM maintains and reinforces cell monolayers during breakdown. This study sheds new insights on our understanding of apoptosis and how biological systems utilize multiple inter- and intra-cytoarchitectures to regulate nanomechanical breakdown.
细胞凋亡是许多生物体正常功能、内稳态和发育所必需的关键生理途径。这个过程在生化水平上受到高度调节，并且已经进行了深入研究。最近的证据表明，细胞凋亡也是一个受控制的纳米力学过程，依赖于生化信号与微环境纳米力学特性之间的反馈。细胞凋亡的纳米力学分解失调会导致细胞和细胞碎片的释放时机不当，从而导致几种炎症性疾病的发病机制。在这项研究中，我们研究了作为单细胞和细胞单层生长的人成纤维细胞早期细胞凋亡的纳米力学后果。这些成纤维细胞存在于体内，参与许多过程，包括伤口愈合和修复，其中细胞凋亡起着主要作用。我们发现，尽管细胞经历了大规模的形态重塑和纳米力学分解，但细胞外基质（ECM）起到维持细胞单层完整性的作用。通过纤连蛋白和 F-肌动蛋白（纤维连接结）之间的强相互作用，ECM 在分解过程中维持和加强细胞单层。这项研究为我们理解细胞凋亡以及生物系统如何利用多种细胞间和细胞内结构来调节纳米力学分解提供了新的见解。
