Determination of single-molecule loading rate during mechanotransduction in cell adhesion

• 成果类型: Article
• 署名作者: Jo, Myung Hyun; Meneses, Paul; Yang, Olivia; Carcamo, Claudia C.; Pangeni, Sushil; Ha, Taekjip
• 署名单位: Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM); Harvard University; Harvard Medical School; Johns Hopkins University; Johns Hopkins University; Howard Hughes Medical Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8372
• DOI: 10.1126/science.adk6921
• 发表日期: 2024-03-22
• 页码: 1374-1379
• 关键词: force measurements; stranded-dna; integrin; tension; receptor; mechanisms; DYNAMICS; strength; probes

摘要

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.