Cells Sensing Mechanical Cues: Stiffness Influences the Lifetime of Cell–Extracellular Matrix Interactions by Affecting the Loading Rate

• Published in: ACS nano Vol. 10; no. 1; pp. 207 - 217
• Main Authors: Jiang, Li, Sun, Zhenglong, Chen, Xiaofei, Li, Jing, Xu, Yue, Zu, Yan, Hu, Jiliang, Han, Dong, Yang, Chun
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 26-01-2016
• Subjects: Actomyosin - genetics; Actomyosin - metabolism; Biomechanical Phenomena; Cell Differentiation; Collagen Type I - genetics; Collagen Type I - metabolism; Core Binding Factor Alpha 1 Subunit - genetics; Core Binding Factor Alpha 1 Subunit - metabolism; Elasticity; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Gene Expression Regulation; Hardness; Heterocyclic Compounds, 4 or More Rings - pharmacology; Humans; Integrin alpha2beta1 - genetics; Integrin alpha2beta1 - metabolism; Mechanotransduction, Cellular; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - metabolism; Nestin - genetics; Nestin - metabolism; Neurofilament Proteins - genetics; Neurofilament Proteins - metabolism; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Oligopeptides - pharmacology; Primary Cell Culture; Single-Cell Analysis; loading rate; single molecule force spectroscopy; single cell force spectroscopy; stem cells differentiation; substrate stiffness; integrin
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/acsnano.5b03157

The question of how cells sense substrate mechanical cues has gained increasing attention among biologists. By introducing contour-based data analysis to single-cell force spectroscopy, we identified a loading-rate threshold for the integrin α2β1–DGEA bond beyond which a dramatic increase in bond lifetime was observed. On the basis of mechanical cues (elasticity or topography), the effective spring constant of substrates k is mapped to the loading rate r under actomyosin pulling speed v, which, in turn, affects the lifetime of the integrin–ligand bond. Additionally, downregulating v with a low-dose blebbistatin treatment promotes the neuronal lineage specification of mesenchymal stem cells on osteogenic stiff substrates. Thus, sensing of the loading rate is central to how cells sense mechanical cues that affect cell–extracellular matrix interactions and stem cell differentiation.