Department of Applied Mechanics, Beijing Institute of Technology, Beijing, China; Wenzhou Key Laboratory of Biophysics, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, China.
Wenzhou Key Laboratory of Biophysics, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, China.
Biophys J. 2023 Jun 20;122(12):2404-2420. doi: 10.1016/j.bpj.2023.03.034. Epub 2023 Mar 24.
Wound closure is a fundamental process in many physiological and pathological processes, but the regulating effects of external force on the closure process are still unclear. Here, we systematically studied the closure process of wounds of different shape under cyclic stretching. We found that the stretching amplitude and direction had significant effect on the healing speed and healing mode. For instance, there was a biphasic dependence of the healing speed on the stretching amplitude. That is, the wound closure was faster under relatively small and large amplitude, while it was slower under intermediate amplitude. At the same time, the stretching could regulate the healing pattern. We showed that the stretching would increase the healing speed along the direction perpendicular to the stretching direction. Specifically, when the stretching was along the major axis of the wound, it accelerated the healing speed along the short axis, which induced a rosette to stitching-line mode transition. In contrast, stretching along the minor axis accelerated the healing speed along the long axis, inducing a stitching-line to rosette mode transition. Our theoretical analyses demonstrated that the wound closure process was coregulated by the mechanical factors including prestress in the cytoskeleton, the protrusion of cells, and the contraction of the actin ring, as well as the geometry of the wound. The cyclic stretch could further modulate the roles of these factors. For example, the stretching changed the stress field in the cell layer, and switched the direction of cell protrusions. This article reveals important cellular mechanisms of the wound healing process under cyclic stretching, and provides an insight into possible approaches of regulating cell collective behaviors via mechanical forces.
伤口闭合是许多生理和病理过程中的基本过程，但外力对闭合过程的调节作用仍不清楚。在这里，我们系统地研究了在循环拉伸下不同形状的伤口的闭合过程。我们发现，拉伸幅度和方向对愈合速度和愈合模式有显著影响。例如，愈合速度与拉伸幅度之间存在双相依赖性。也就是说，在相对较小和较大的幅度下，伤口闭合得更快，而在中间幅度下则更慢。同时，拉伸可以调节愈合模式。我们表明，拉伸会增加垂直于拉伸方向的愈合速度。具体来说，当拉伸沿伤口的长轴进行时，它会加速短轴的愈合速度，从而诱导从缝合线模式到玫瑰花结模式的转变。相比之下，沿短轴拉伸会加速长轴的愈合速度，从而诱导从玫瑰花结模式到缝合线模式的转变。我们的理论分析表明，伤口闭合过程受到包括细胞骨架中的预应力、细胞突起和肌动球蛋白环收缩在内的机械因素以及伤口几何形状的共同调节。循环拉伸可以进一步调节这些因素的作用。例如，拉伸改变了细胞层中的应力场，并改变了细胞突起的方向。本文揭示了循环拉伸下伤口愈合过程中的重要细胞机制，并为通过机械力调节细胞集体行为提供了新的见解。
