title: Myosin II controls cellular branching morphogenesis and migration in three dimensions by minimizing cell-surface curvature.
abstract: In many cases, cell function is intimately linked to cell shape control. We used endothelial cell branching morphogenesis as a model to understand the role of myosin II in shape control of invasive cells migrating in 3D collagen gels. We applied principles of differential geometry and mathematical morphology to 3D image sets to parameterize cell branch structure and local cell-surface curvature. We find that Rho/ROCK-stimulated myosin II contractility minimizes cell-scale branching by recognizing and minimizing local cell-surface curvature. Using microfabrication to constrain cell shape identifies a positive feedback mechanism in which low curvature stabilizes myosin II cortical association, where it acts to maintain minimal curvature. The feedback between regulation of myosin II by curvature and control of curvature by myosin II drives cycles of localized cortical myosin II assembly and disassembly. These cycles in turn mediate alternating phases of directionally biased branch initiation and retraction to guide 3D cell migration.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Hunter
authors.initials: H
authors.lastname: Elliott
authors.affiliation: Cell Biology and Physiology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Fischer
authors.affiliation: 1] Cell Biology and Physiology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA [2] Department of Biological Sciences, University of the Sciences, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Myers
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Ravi A
authors.initials: RA
authors.lastname: Desai
authors.affiliation: 1] Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA [2] Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Gao
authors.affiliation: 1] Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA [2] Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA [3] Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Genetics and Developmental Biology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Adelstein
authors.affiliation: Cell Biology and Physiology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Clare M
authors.initials: CM
authors.lastname: Waterman
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Gaudenz
authors.initials: G
authors.lastname: Danuser
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement; D042783:Endothelial Cells / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D021621:Imaging, Three-Dimensional; D051379:Mice; D009024:Morphogenesis; D024462:Myosin Type II / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors
chemical_list: D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D024462:Myosin Type II