Letter abstract


Nature Cell Biology 12, 598 - 604 (2010)
Published online: 16 May 2010 | doi:10.1038/ncb2062

A distinctive role for focal adhesion proteins in three-dimensional cell motility

Stephanie I. Fraley1,2,6, Yunfeng Feng2,3,4,6, Ranjini Krishnamurthy1, Dong-Hwee Kim1,2, Alfredo Celedon1,5, Gregory D. Longmore2,3,4 & Denis Wirtz1,2

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Focal adhesions are large multi-protein assemblies that form at the basal surface of cells on planar dishes, and that mediate cell signalling, force transduction and adhesion to the substratum. Although much is known about focal adhesion components in two-dimensional (2D) systems, their role in migrating cells in a more physiological three-dimensional (3D) matrix is largely unknown. Live-cell microscopy shows that for cells fully embedded in a 3D matrix, focal adhesion proteins, including vinculin, paxillin, talin, α-actinin, zyxin, VASP, FAK and p130Cas, do not form aggregates but are diffusely distributed throughout the cytoplasm. Despite the absence of detectable focal adhesions, focal adhesion proteins still modulate cell motility, but in a manner distinct from cells on planar substrates. Rather, focal adhesion proteins in matrix-embedded cells regulate cell speed and persistence by affecting protrusion activity and matrix deformation, two processes that have no direct role in controlling 2D cell speed. This study shows that membrane protrusions constitute a critical motility/matrix-traction module that drives cell motility in a 3D matrix.

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  1. Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
  2. Johns Hopkins Physical Sciences in Oncology Center, Johns Hopkins University, Baltimore, Maryland 21218, USA.
  3. Departments of Medicine and Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  4. Washington University BRIGHT Institute, Washington University School of Medicine, St. Louis, MO 63110, USA.
  5. Department of Mechanical Engineering, Pontificia Universidad Católica de Chile, P.O. Box 306, Santiago, 6904411, Chile.
  6. These authors contributed equally to this work.

Correspondence to: Gregory D. Longmore2,3,4 e-mail: glongmor@dom.wustl.edu

Correspondence to: Denis Wirtz1,2 e-mail: wirtz@jhu.edu



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