Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Science. 2024 Mar 22;383(6689):1374-1379. doi: 10.1126/science.adk6921. Epub 2024 Mar 21.
Cells connect with their environment through surface receptors and use physical tension in receptor-ligand bonds for various cellular processes. Single-molecule techniques have revealed bond strength by measuring "rupture force," but it has long been recognized that rupture force is dependent on loading rate-how quickly force is ramped up. Thus, the physiological loading rate needs to be measured to reveal the mechanical strength of individual bonds in their functional context. We have developed an overstretching tension sensor (OTS) to allow more accurate force measurement in physiological conditions with single-molecule detection sensitivity even in mechanically active regions. We used serially connected OTSs to show that the integrin loading rate ranged from 0.5 to 4 piconewtons per second and was about three times higher in leukocytes than in epithelial cells.
细胞通过表面受体与环境相连，并利用受体-配体键中的物理张力来进行各种细胞过程。单分子技术通过测量“断裂力”来揭示键的强度，但人们早就认识到，断裂力取决于加载速率——力增加的速度有多快。因此，需要测量生理加载速率，以在其功能环境中揭示单个键的机械强度。我们开发了一种过拉伸张力传感器（OTS），即使在机械活跃区域，也可以在具有单分子检测灵敏度的生理条件下进行更准确的力测量。我们使用串联连接的 OTS 表明，整合素的加载速率范围为 0.5 到 4 皮牛顿每秒，在白细胞中的加载速率比在上皮细胞中高约三倍。
