title: Cells Sensing Mechanical Cues: Stiffness Influences the Lifetime of Cell-Extracellular Matrix Interactions by Affecting the Loading Rate.
abstract: 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.
authors.affiliation: Institute of Biomechanics and Medical Engineering, School of Aerospace, Tsinghua University , Beijing 100084, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Institute of Biomechanics and Medical Engineering, School of Aerospace, Tsinghua University , Beijing 100084, People's Republic of China.|Suzhou Institute of Biomedical Engineering and Technology, China Academy of Science , Suzhou 215163, People's Republic of China.
authors.forename: Zhenglong
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Institute of Biomechanics and Medical Engineering, School of Aerospace, Tsinghua University , Beijing 100084, People's Republic of China.|Beijing Institute of Aerospace Systems Engineering , Beijing 100076, People's Republic of China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Institute of Biomechanics and Medical Engineering, School of Aerospace, Tsinghua University , Beijing 100084, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Biomechanics and Medical Engineering, School of Aerospace, Tsinghua University , Beijing 100084, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Institute of Biomechanics and Medical Engineering, School of Aerospace, Tsinghua University , Beijing 100084, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zu
authors.affiliation: Institute of Biomechanics and Medical Engineering, School of Aerospace, Tsinghua University , Beijing 100084, People's Republic of China.
authors.forename: Jiliang
authors.initials: J
authors.lastname: Hu
authors.affiliation: National Center for Nanoscience and Technology , Beijing 100190, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.affiliation: Institute of Biomechanics and Medical Engineering, School of Aerospace, Tsinghua University , Beijing 100084, People's Republic of China.
authors.forename: Chun
authors.initials: C
authors.lastname: Yang
mesh_terms: D000205:Actomyosin / Q000235:genetics / Q000378:metabolism; D001696:Biomechanical Phenomena; D002454:Cell Differentiation; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D004548:Elasticity; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D006244:Hardness; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D038982:Integrin alpha2beta1 / Q000235:genetics / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D061251:Primary Cell Culture; D059010:Single-Cell Analysis
chemical_list: D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D006576:Heterocyclic Compounds, 4 or More Rings; D038982:Integrin alpha2beta1; C577484:NES protein, human; D064231:Nestin; D016900:Neurofilament Proteins; D009842:Oligopeptides; C493709:RUNX2 protein, human; C113781:aspartyl-glycyl-glutamyl-alanine; C044882:neurofilament protein L; C472645:blebbistatin; D000205:Actomyosin
keywords: integrin; loading rate; single cell force spectroscopy; single molecule force spectroscopy; stem cells differentiation; substrate stiffness