Beijing National Laboratory for Condensed Matter Physics and Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, 100190, China.
School of Physical Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
Small. 2022 Feb;18(5):e2106498. doi: 10.1002/smll.202106498. Epub 2021 Dec 18.
Cell morphology and migration depend critically on the adhesions on the extracellular matrix (ECM), determined by the transmembrane protein integrins. The epithelial to mesenchymal transition (EMT) is a prominent transformation process in which adherent cells acquire a mesenchymal phenotype and a promoted migration. EMT plays important roles in embryonic development and cancer metastasis, and its hallmarks include the acquisition of front-back cell polarity and loss of cell-cell contact. However, how integrins dynamically regulate cell-ECM adhesions and cellular behaviors during EMT is still unclear. Using single-particle tracking of β1-integrins labeled with quantum dots, the temporal-spatial on-membrane dynamics of integrins in the EMT of MCF10A cells is revealed. β1-integrins exhibit significantly enhanced dynamics, which temporally behave more diffusive and less immobilized, and spatially become distributed asymmetrically with front regions being more dynamic. These dynamic alterations are shown to arise from microtubule remodeling in EMT. The results shed new light on the EMT mechanism from the cell-ECM adhesion perspective, and suggest that the enhanced integrin diffusion may represent as a new hallmark of EMT.
细胞形态和迁移取决于细胞外基质(ECM)上的黏附,这由跨膜蛋白整合素决定。上皮间质转化(EMT)是一种明显的转化过程,在此过程中,黏附细胞获得间充质表型和促进迁移。EMT 在胚胎发育和癌症转移中发挥重要作用,其特征包括获得前后细胞极性和丧失细胞间接触。然而,整合素如何在 EMT 过程中动态调节细胞-ECM 黏附及细胞行为仍不清楚。通过量子点标记的β1 整合素的单颗粒追踪,揭示了 MCF10A 细胞 EMT 过程中整合素在膜上的时空动态。β1 整合素表现出明显增强的动力学,在时间上表现出更扩散和更少固定的行为,在空间上分布不对称,前区更具动态性。这些动态变化是由 EMT 中的微管重排引起的。这些结果从细胞-ECM 黏附的角度揭示了 EMT 的机制,并表明增强的整合素扩散可能代表 EMT 的一个新特征。