Contact guidance diversity in rotationally aligned collagen matrices

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Nuhn, Jacob
Perez, Anai
Schneider, Ian
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Schneider, Ian
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Genetics, Development and Cell Biology

The Department of Genetics, Development, and Cell Biology seeks to teach subcellular and cellular processes, genome dynamics, cell structure and function, and molecular mechanisms of development, in so doing offering a Major in Biology and a Major in Genetics.

The Department of Genetics, Development, and Cell Biology was founded in 2005.

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Genetics, Development and Cell BiologyChemical and Biological Engineering

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.


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.

Sun Jan 01 00:00:00 UTC 2017