ScienceDaily (Dec. 17, 2009) — Scientists at Brown University and the California Institute of Technology have for the first time tracked how cells move in three dimensions by measuring the force exerted by them on their surroundings. The scientists' experiments revealed that cells move in a push-pull fashion, such as probing at depth, redistributing weight at various points and coiling and elongating.
Our cells are more like us than we may think. They're sensitive to their environment, poking and prodding deliberately at their surroundings with hand-like feelers and chemical signals as they decide whether and where to move. Such caution serves us well but has vexed engineers who seek to create synthetic tissue, heart valves, implants and other devices that the human body will accept.
Three-dimensional cell. Scientists at Brown University and the California Institute of Technology have for the first time tracked how cells move by measuring the force exerted by them on their surroundings. The method could lead to better understanding how healthy cells differ from malignant cells. (Credit: Christian Franck, Brown University)
To overcome that obstacle, scientists have sought to learn more about how cells explore what's around them. While numerous studies have looked at cellular movement in two dimensions and a few recent experiments involved cellular motion in three dimensions, scientists remained unsure just how much cells interacted with their surroundings. Now, a study involving Brown University and the California Institute of Technology has recorded for the first time how cells move in three dimensions by measuring the force exerted by cells on their environs. The research gives scientists their most complete assessment to date about how cells move.
"We've learned that cells move in much more complex ways than previously believed," said Christian Franck, assistant professor in engineering at Brown and the co-lead author of the study published online in the Proceedings of the National Academy of Sciences. "Now, we can start to really put numbers on how much cells push and pull on their environment and how much cells stick to tissues as they move around and interact."
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Quantifying cellular traction forces in three dimensions
Stacey A. Maskarinec a,1, Christian Franck b,1,2, David A. Tirrell a and Guruswami Ravichandran c
- Author Affiliations
aDivision of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC 210-41, Pasadena, CA 91125;
bDivision of Engineering, Brown University, 182 Hope Street, Box D, Providence, RI 02912; and
cDivision of Engineering and Applied Science, California Institute of Technology, 1200 East California Boulevard, MC 105-50, Pasadena, CA 91125
↵1S.A.M. and C.F. contributed equally to this work.
Edited by Steven G. Boxer, Stanford University, Stanford, CA, and approved November 2, 2009 (received for review April 27, 2009)
Abstract
Cells engage in mechanical force exchange with their extracellular environment through tension generated by the cytoskeleton. A method combining laser scanning confocal microscopy (LSCM) and digital volume correlation (DVC) enables tracking and quantification of cell-mediated deformation of the extracellular matrix in all three spatial dimensions. Time-lapse confocal imaging of migrating 3T3 fibroblasts on fibronectin (FN)-modified polyacrylamide gels of varying thickness reveals significant in-plane (x, y) and normal (z) displacements, and illustrates the extent to which cells, even in nominally two-dimensional (2-D) environments, explore their surroundings in all three dimensions. The magnitudes of the measured displacements are independent of the elastic moduli of the gels. Analysis of the normal displacement profiles suggests that normal forces play important roles even in 2-D cell migration.
digital volume correlation laser scanning confocal microscopy three-dimensional
Footnotes
2To whom correspondence should be addressed. E-mail: franck@brown.edu
Author contributions: S.A.M., C.F., D.A.T., and G.R. designed research; S.A.M. and C.F. performed research; S.A.M. and C.F. contributed new reagents/analytic tools; S.A.M., C.F., D.A.T., and G.R. analyzed data; and S.A.M., C.F., D.A.T., and G.R. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
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