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Published 11 September 2006. doi:10.1083/jcb.200601159
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 174, Number 6, 767-772
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Direct measurement of the lamellipodial protrusive force in a migrating cell



Marcus Prass1, Ken Jacobson2,3, Alex Mogilner4,5, and Manfred Radmacher1

1 Institute of Biophysics, University of Bremen, D-28359 Bremen, Germany
2 Department of Cell and Developmental Biology and 3 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
4 Department of Mathematics and 5 Center for Genetics and Development, University of California, Davis, Davis, CA 95616

Correspondence to Manfred Radmacher: mr{at}biophysik.uni-bremen.de

There has been a great deal of interest in the mechanism of lamellipodial protrusion (Pollard, T., and G. Borisy. 2003. Cell. 112:453–465). However, one of this mechanism's endpoints, the force of protrusion, has never been directly measured. We place an atomic force microscopy cantilever in the path of a migrating keratocyte. The deflection of the cantilever, which occurs over a period of ~10 s, provides a direct measure of the force exerted by the lamellipodial leading edge. Stall forces are consistent with ~100 polymerizing actin filaments per micrometer of the leading edge, each working as an elastic Brownian ratchet and generating a force of several piconewtons. However, the force-velocity curves obtained from this measurement, in which velocity drops sharply under very small loads, is not sensitive to low loading forces, and finally stalls rapidly at large loads, are not consistent with current theoretical models for the actin polymerization force. Rather, the curves indicate that the protrusive force generation is a complex multiphase process involving actin and adhesion dynamics.

Abbreviations used in this paper: AFM, atomic force microscopy; RICM, reflection interference contrast microscopy.


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