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  • Open Access

Three-dimensional cancer cell migration directed by dual mechanochemical guidance

Pedram Esfahani1, Herbert Levine2,3,*, Mrinmoy Mukherjee2, and Bo Sun1,†

  • 1Department of Physics, Oregon State University, Corvallis, Oregon 97331, USA
  • 2Center for Theoretical Biological Physics, Northeastern University, Boston, Massachusetts 02115, USA
  • 3Departments of Physics and Bioengineering, Northeastern University, Boston, Massachusetts 02115, USA

  • *Corresponding author: h.levine@northeastern.edu
  • †Corresponding author: sunb@oregonstate.edu
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Phys. Rev. Research 4, L022007 – Published 12 April, 2022

DOI: https://doi.org/10.1103/PhysRevResearch.4.L022007

Abstract

Directed cell migration guided by external cues plays a central role in many physiological and pathophysiological processes. The microenvironment of cells often simultaneously contains various cues and the motility response of cells to multiplexed guidance is poorly understood. Here we combine experiments and mathematical models to study the three-dimensional migration of breast cancer cells in the presence of both contact guidance and a chemoattractant gradient. We find that the chemotaxis of cells is complicated by the presence of contact guidance as the microstructure of extracellular matrix (ECM) vary spatially. In the presence of dual guidance, the impact of ECM alignment is determined externally by the coherence of ECM fibers and internally by cell mechanosensing Rho/Rock pathways. When contact guidance is parallel to the chemical gradient, coherent ECM fibers significantly increase the efficiency of chemotaxis. When contact guidance is perpendicular to the chemical gradient, cells exploit the ECM disorder to locate paths for chemotaxis. Our results underscore the importance of fully characterizing the cancer cell microenvironment in order to better understand invasion and metastasis.

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Outline

Information

Phys. Rev. Research 4, L022007– Published 12 April, 2022
  • Received 7 November 2021
  • Accepted 29 March 2022
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Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.

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