title: Contact angle at the leading edge controls cell protrusion rate.
abstract: Plasma membrane tension and the pressure generated by actin polymerization are two antagonistic forces believed to define the protrusion rate at the leading edge of migrating cells [1-5]. Quantitatively, resistance to actin protrusion is a product of membrane tension and mean local curvature (Laplace's law); thus, it depends on the local geometry of the membrane interface. However, the role of the geometry of the leading edge in protrusion control has not been yet investigated. Here, we manipulate both the cell shape and substrate topography in the model system of persistently migrating fish epidermal keratocytes. We find that the protrusion rate does not correlate with membrane tension, but, instead, strongly correlates with cell roundness, and that the leading edge of the cell exhibits pinning on substrate ridges-a phenomenon characteristic of spreading of liquid drops. These results indicate that the leading edge could be considered a triple interface between the substrate, membrane, and extracellular medium and that the contact angle between the membrane and the substrate determines the load on actin polymerization and, therefore, the protrusion rate. Our findings thus illuminate a novel relationship between the 3D shape of the cell and its dynamics, which may have implications for cell migration in 3D environments.
authors.affiliation: Laboratory of Cell Biophysics, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland. Electronic address: chiara.gabella@epfl.ch.
authors.forename: Chiara
authors.initials: C
authors.lastname: Gabella
authors.affiliation: Laboratory of Cell Biophysics, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland; Laboratory of Physics of Complex Matter, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Elena
authors.initials: E
authors.lastname: Bertseva
authors.affiliation: Laboratory of Cell Biophysics, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Céline
authors.initials: C
authors.lastname: Bottier
authors.affiliation: Laboratory of Cell Biophysics, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Niccolò
authors.initials: N
authors.lastname: Piacentini
authors.affiliation: Laboratory of Cell Biophysics, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Alicia
authors.initials: A
authors.lastname: Bornert
authors.affiliation: Laboratory of Physics of Complex Matter, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Jeney
authors.affiliation: Laboratory of Physics of Complex Matter, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: László
authors.initials: L
authors.lastname: Forró
authors.affiliation: MOSAIC Group, Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
authors.forename: Ivo F
authors.initials: IF
authors.lastname: Sbalzarini
authors.affiliation: Laboratory of Cell Biophysics, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Meister
authors.affiliation: Laboratory of Cell Biophysics, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Verkhovsky
mesh_terms: D000199:Actins / Q000737:chemistry*; D000818:Animals; D002462:Cell Membrane / Q000502:physiology*; D002465:Cell Movement; D048430:Cell Shape; D060126:Characidae / Q000502:physiology*; D000078404:Epidermal Cells; D004847:Epithelial Cells / Q000166:cytology*; D058105:Polymerization; D011312:Pressure
chemical_list: D000199:Actins