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Microfabricated tissues for investigating traction forces involved in cell migration and tissue morphogenesis

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Abstract

Cell-generated forces drive an array of biological processes ranging from wound healing to tumor metastasis. Whereas experimental techniques such as traction force microscopy are capable of quantifying traction forces in multidimensional systems, the physical mechanisms by which these forces induce changes in tissue form remain to be elucidated. Understanding these mechanisms will ultimately require techniques that are capable of quantifying traction forces with high precision and accuracy in vivo or in systems that recapitulate in vivo conditions, such as microfabricated tissues and engineered substrata. To that end, here we review the fundamentals of traction forces, their quantification, and the use of microfabricated tissues designed to study these forces during cell migration and tissue morphogenesis. We emphasize the differences between traction forces in two- and three-dimensional systems, and highlight recently developed techniques for quantifying traction forces.

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Abbreviations

2D:

Two-dimensional

3D:

Three-dimensional

AFM:

Atomic force microscopy

ECM:

Extracellular matrix

FRET:

Fluorescence resonance energy transfer

MDCK:

Madin–Darby canine kidney

PA:

Polyacrylamide

PEG:

Polyethylene glycol

TFM:

Traction force microscopy

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Acknowledgements

Work from the authors’ group was supported in part by grants from the NIH (GM083997, HL110335, HL118532, HL120142, and CA 187692), the NSF (CMMI-1435853), the David and Lucile Packard Foundation, the Alfred P. Sloan Foundation, the Camille and Henry Dreyfus Foundation, and the Burroughs Wellcome Fund. M.J.S. was supported in part by the NSF Graduate Research Fellowship Program. C.M.N. was supported in part by a Faculty Scholars Award from the Howard Hughes Medical Institute.

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  1. Department of Chemical and Biological Engineering, Princeton University, 303 Hoyt Laboratory, William Street, Princeton, NJ, 08544, USA

    Bryan A. Nerger, Michael J. Siedlik & Celeste M. Nelson

  2. Department of Molecular Biology, Princeton University, 303 Hoyt Laboratory, William Street, Princeton, NJ, 08544, USA

    Celeste M. Nelson

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Nerger, B.A., Siedlik, M.J. & Nelson, C.M. Microfabricated tissues for investigating traction forces involved in cell migration and tissue morphogenesis. Cell. Mol. Life Sci. 74, 1819–1834 (2017). https://doi.org/10.1007/s00018-016-2439-z

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