title: Mechanical tugging force regulates the size of cell-cell junctions.
abstract: Actomyosin contractility affects cellular organization within tissues in part through the generation of mechanical forces at sites of cell-matrix and cell-cell contact. While increased mechanical loading at cell-matrix adhesions results in focal adhesion growth, whether forces drive changes in the size of cell-cell adhesions remains an open question. To investigate the responsiveness of adherens junctions (AJ) to force, we adapted a system of microfabricated force sensors to quantitatively report cell-cell tugging force and AJ size. We observed that AJ size was modulated by endothelial cell-cell tugging forces: AJs and tugging force grew or decayed with myosin activation or inhibition, respectively. Myosin-dependent regulation of AJs operated in concert with a Rac1, and this coordinated regulation was illustrated by showing that the effects of vascular permeability agents (S1P, thrombin) on junctional stability were reversed by changing the extent to which these agents coupled to the Rac and myosin-dependent pathways. Furthermore, direct application of mechanical tugging force, rather than myosin activity per se, was sufficient to trigger AJ growth. These findings demonstrate that the dynamic coordination of mechanical forces and cell-cell adhesive interactions likely is critical to the maintenance of multicellular integrity and highlight the need for new approaches to study tugging forces.
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Liu
authors.forename: John L
authors.initials: JL
authors.lastname: Tan
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Cohen
authors.forename: Michael T
authors.initials: MT
authors.lastname: Yang
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Sniadecki
authors.forename: Sami Alom
authors.initials: SA
authors.lastname: Ruiz
authors.forename: Celeste M
authors.initials: CM
authors.lastname: Nelson
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Chen
mesh_terms: D022005:Adherens Junctions / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure*; D019943:Amino Acid Substitution; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001696:Biomechanical Phenomena; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology; D008845:Microinjections; D024462:Myosin Type II / Q000502:physiology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D020744:rac GTP-Binding Proteins / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000008:administration & dosage / Q000235:genetics / Q000502:physiology; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D049452:Green Fluorescent Proteins; D008246:Lysophospholipids; D024462:Myosin Type II; D011994:Recombinant Proteins; D013110:Sphingosine; D013917:Thrombin; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D000099152:Cadherin 5; C066737:RHOA protein, human; C060506:sphingosine 1-phosphate
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