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Published October 1, 2015 | Published + Supplemental Material
Journal Article Open

Quantifying cell-induced matrix deformation in three dimensions based on imaging matrix fibers

Abstract

During processes such as development and cancer metastasis, cells migrate into three-dimensional fibrous matrices. Previous studies have speculated on the mechanical forces required for migration by observing matrix fiber alignment, densification, and degradation, but these forces remain difficult to quantify. Here we present a new experimental technique to simultaneously measure full-field 3D displacements and structural remodeling of a fibrous matrix, both of which result from cellular forces. We apply this "2-in-1" experimental technique to follow single cells as they invade a physiologically relevant fibrin matrix. We find that cells generate tube-like structures in the matrix by plastically deforming their surroundings, and they re-use these tubes to extend protrusions. Cells generate these tubular structures by applying both pulling and pushing forces.

Additional Information

© 2015 The Royal Society of Chemistry. Received 17th January 2015, Accepted 19th May 2015, First published online 19 May 2015. We thank Scott Fraser for providing the transfected fibroblasts. We thank the Biological Imaging Center of the Beckman Institute at Caltech for use of the two-photon microscope. This work was funded by grants from the National Science Foundation (Division of Materials Research 0520565 and 1206121) and from the California Institute for Regenerative Medicine (RB5-07398). J.N. was supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-1144469. A.L. was supported in part by a Rothschild Foundation fellowship. We thank Samuel A. Safran and Xinpeng Xu for reviewing the paper and providing useful comments.

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