Cell-cell adhesion complexes are macromolecular adhesive organelles that integrate cells into tissues. This mechanochemical coupling in cell-cell adhesion is required for a large number of cell behaviors, and perturbations of the cell-cell adhesion structure or related mechanotransduction pathways can lead to critical pathological conditions such as skin and heart diseases, arthritis, and cancer. Mechanical stretching has been a widely used method to stimulate the mechanotransduction process originating from the cell-cell adhesion and cell-extracellular matrix (ECM) complexes. These studies aimed to reveal the biophysical processes governing cell proliferation, wound healing, gene expression regulation, and cell differentiation in various tissues, including cardiac, muscle, vascular, and bone. This review explores techniques in mechanical stretching in two-dimensional settings with different stretching regimens on different cell types. The mechanotransduction responses from these different cell types will be discussed with an emphasis on their biophysical transformations during mechanical stretching and the cross talk between the cell-cell and cell-ECM adhesion complexes. Therapeutic aspects of mechanical stretching are reviewed considering these cellular responses after the application of mechanical forces, with a focus on wound healing and tissue regeneration. Impact Statement Mechanical stretching has been proposed as a therapeutic option for tissue regeneration and wound healing. It has been accepted that mechanotransduction processes elicited by mechanical stretching govern cellular response and behavior, and these studies have predominantly focused on the cell-extracellular matrix (ECM) sites. This review serves the mechanobiology community by shifting the focus of mechanical stretching effects from cell-ECM adhesions to the less examined cell-cell adhesions, which we believe play an equally important role in orchestrating the response pathways.

中文翻译：

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细胞间粘附机械拉伸的组织再生。

细胞-细胞粘附复合物是将细胞整合到组织中的大分子粘附细胞器。细胞间粘附中的这种机械化学耦合是大量细胞行为所必需的，细胞间粘附结构或相关机械转导途径的扰动可能导致严重的病理状况，例如皮肤和心脏病、关节炎和癌症。机械拉伸是一种广泛使用的方法，用于刺激源自细胞-细胞粘附和细胞-细胞外基质 (ECM) 复合物的力转导过程。这些研究旨在揭示各种组织（包括心脏、肌肉、血管和骨骼）中细胞增殖、伤口愈合、基因表达调控和细胞分化的生物物理过程。本综述探讨了在二维环境中对不同细胞类型采用不同拉伸方案的机械拉伸技术。将讨论这些不同细胞类型的机械转导反应，重点是它们在机械拉伸期间的生物物理转变以及细胞-细胞和细胞-ECM 粘附复合物之间的串扰。考虑到施加机械力后的这些细胞反应，回顾机械拉伸的治疗方面，重点是伤口愈合和组织再生。影响陈述 机械拉伸已被提议作为组织再生和伤口愈合的治疗选择。人们普遍认为，机械拉伸引起的力传导过程控制细胞反应和行为，并且这些研究主要集中在细胞-细胞外基质 (ECM) 位点。这篇综述通过将机械拉伸效应的焦点从细胞-ECM 粘附转移到较少检查的细胞-细胞粘附，为机械生物学界服务，我们认为细胞-细胞粘附在协调反应途径中发挥着同样重要的作用。