Pajic-Lijakovic Ivana, Milivojevic Milan, Martinac Boris, McClintock Peter V E
Department of Chemical Engineering, Faculty of Technology and Metallurgy, University of Belgrade, Belgrade, Serbia.
Mechanosensory Biophysics Laboratory, Victor Chang Cardiac Research Institute, Sydney, Australia.
Biophys Rev. 2025 Mar 19;17(3):847-865. doi: 10.1007/s12551-025-01304-y. eCollection 2025 Jun.
The application of cyclic stretch could represent a novel therapeutic method for fighting cancer. Research indicates that this mechanical stimulus selectively induces cell death in cancer mesenchymal-like cells while enhancing the migration and proliferation of healthy epithelial cells. Although the mechanisms have been examined through the lenses of cell signalling, gene expression, and biochemical processes, a significant gap persists in our understanding of the physical factors that drive cellular responses. This study aims to clarify the importance of physical factors, particularly the viscoelastic characteristics of the cell membrane, including actin cytoskeleton and lipid bilayer, and how their coupling affects bilayer bending and activation of the mechanosensitive Piezo1 channels in response to cyclic stretch in both epithelial and cancer cells. The bending of the bilayer surrounding Piezo1 molecules affects their conformations, which in turn influences calcium influx. This bending is contingent upon the coupling between the cell membrane and extracellular matrix. The primary factors contributing to the mechanically induced apoptosis of cancer cells are the perturbation of intracellular calcium homeostasis and disruption of focal adhesions.
周期性拉伸的应用可能代表一种对抗癌症的新型治疗方法。研究表明，这种机械刺激能选择性地诱导癌症间充质样细胞死亡，同时增强健康上皮细胞的迁移和增殖。尽管已经通过细胞信号传导、基因表达和生化过程等方面对其机制进行了研究，但在我们对驱动细胞反应的物理因素的理解上仍存在重大差距。本研究旨在阐明物理因素的重要性，特别是细胞膜的粘弹性特征，包括肌动蛋白细胞骨架和脂质双层，以及它们的耦合如何影响双层弯曲和机械敏感的Piezo1通道的激活，以响应上皮细胞和癌细胞中的周期性拉伸。围绕Piezo1分子的双层弯曲会影响其构象，进而影响钙内流。这种弯曲取决于细胞膜与细胞外基质之间的耦合。导致癌细胞机械诱导凋亡的主要因素是细胞内钙稳态的扰动和粘着斑的破坏。
