Nature 453, 475-480 (22 May 2008) | doi:10.1038/nature06952; Received 14 December 2007; Accepted 31 March 2008

Mechanism of shape determination in motile cells

Kinneret Keren1,3,7, Zachary Pincus1,4,7, Greg M. Allen1, Erin L. Barnhart1, Gerard Marriott5, Alex Mogilner6 & Julie A. Theriot1,2

  1. Department of Biochemistry, and,
  2. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA
  3. Department of Physics, Technion- Israel Institute of Technology, Haifa 32000, Israel
  4. Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA
  5. Department of Physiology, University of Wisconsin at Madison, Madison, Wisconsin 53706, USA
  6. Department of Neurobiology, Physiology and Behavior and Department of Mathematics, University of California, Davis, California 95616, USA
  7. These authors contributed equally to this work.

Correspondence to: Julie A. Theriot1,2 Correspondence and requests for materials should be addressed to J.A.T. (Email:


The shape of motile cells is determined by many dynamic processes spanning several orders of magnitude in space and time, from local polymerization of actin monomers at subsecond timescales to global, cell-scale geometry that may persist for hours. Understanding the mechanism of shape determination in cells has proved to be extremely challenging due to the numerous components involved and the complexity of their interactions. Here we harness the natural phenotypic variability in a large population of motile epithelial keratocytes from fish (Hypsophrys nicaraguensis) to reveal mechanisms of shape determination. We find that the cells inhabit a low-dimensional, highly correlated spectrum of possible functional states. We further show that a model of actin network treadmilling in an inextensible membrane bag can quantitatively recapitulate this spectrum and predict both cell shape and speed. Our model provides a simple biochemical and biophysical basis for the observed morphology and behaviour of motile cells.


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