Campus Units

Chemical and Biological Engineering, Genetics, Development and Cell Biology

Document Type

Article

Research Focus Area

Health Care Technology and Biomedical Engineering

Publication Version

Accepted Manuscript

Publication Date

1-15-2018

Journal or Book Title

Acta Biomaterialia

Volume

66

First Page

248

Last Page

257

DOI

10.1016/j.actbio.2017.11.039

Abstract

Cancer cell metastasis is responsible for approximately 90% of deaths related to cancer. The migration of cancer cells away from the primary tumor and into healthy tissue is driven in part by contact guidance, or directed migration in response to aligned extracellular matrix. While contact guidance has been a focus of many studies, much of this research has explored environments that present 2D contact guidance structures. Contact guidance environments in 3D more closely resemble in vivo conditions and model cell-ECM interactions better than 2D environments. While most cells engage in directed migration on potent 2D contact guidance cues, there is diversity in response to contact guidance cues based on whether the cell migrates with a mesenchymal or amoeboid migration mode. In this paper, rotational alignment of collagen gels was used to study the differences in contact guidance between MDA-MB-231 (mesenchymal) and MTLn3 (amoeboid) cells. MDA-MB-231 cells migrate with high directional fidelity in aligned collagen gels, while MTLn3 cells show no directional migration. The collagen stiffness was increased through glycation, resulting in decreased MDA-MB-231 directionality in aligned collagen gels. Interestingly, partial inhibition of cell contractility dramatically decreased directionality in MDA-MB-231 cells. The directionality of MDA-MB-231 cells was most sensitive to ROCK inhibition, but unlike in 2D contact guidance environments, cell directionality and speed are more tightly coupled. Modulation of the contractile apparatus appears to more potently affect contact guidance than modulation of extracellular mechanical properties of the contact guidance cue.

Comments

This is a manuscript of an article published as Nuhn, Jacob AM, Anai M. Perez, and Ian C. Schneider. "Contact guidance diversity in rotationally aligned collagen matrices." Acta Biomaterialia 66 (2018): 248-257. DOI: 10.1016/j.actbio.2017.11.039. Posted with permission.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Copyright Owner

Acta Materialia Inc.

Language

en

File Format

application/pdf

Available for download on Thursday, November 28, 2019

Published Version

Included in

Biomaterials Commons

Share

COinS