title: Guidance of collective cell migration by substrate geometry.
abstract: Collective behavior refers to the emergence of complex migration patterns over scales larger than those of the individual elements constituting a system. It plays a pivotal role in biological systems in regulating various processes such as gastrulation, morphogenesis and tissue organization. Here, by combining experimental approaches and numerical modeling, we explore the role of cell density ('crowding'), strength of intercellular adhesion ('cohesion') and boundary conditions imposed by extracellular matrix (ECM) proteins ('constraints') in regulating the emergence of collective behavior within epithelial cell sheets. Our results show that the geometrical confinement of cells into well-defined circles induces a persistent, coordinated and synchronized rotation of cells that depends on cell density. The speed of such rotating large-scale movements slows down as the density increases. Furthermore, such collective rotation behavior depends on the size of the micropatterned circles: we observe a rotating motion of the overall cell population in the same direction for sizes of up to 200 μm. The rotating cells move as a solid body, with a uniform angular velocity. Interestingly, this upper limit leads to length scales that are similar to the natural correlation length observed for unconfined epithelial cell sheets. This behavior is strongly altered in cells that present a downregulation of adherens junctions and in cancerous cell types. We anticipate that our system provides a simple and easy approach to investigate collective cell behavior in a well-controlled and systematic manner.
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore117411.
authors.forename: Kevin
authors.initials: K
authors.lastname: Doxzen
authors.forename: Sri Ram Krishna
authors.initials: SR
authors.lastname: Vedula
authors.forename: Man Chun
authors.initials: MC
authors.lastname: Leong
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hirata
authors.forename: Nir S
authors.initials: NS
authors.lastname: Gov
authors.forename: Alexandre J
authors.initials: AJ
authors.lastname: Kabla
authors.forename: Benoit
authors.initials: B
authors.lastname: Ladoux
authors.forename: Chwee Teck
authors.initials: CT
authors.lastname: Lim
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002462:Cell Membrane; D002465:Cell Movement / Q000502:physiology*; D003198:Computer Simulation; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology*; D058750:Epithelial-Mesenchymal Transition; D005353:Fibronectins / Q000737:chemistry; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D009010:Monte Carlo Method
chemical_list: D005353:Fibronectins