Contact Guidance Drives Upward Cellular Migration at the Mesoscopic Scale

Xiaoxiao Chen; Youjun Xia; Wenqiang Du; Han Liu; Ran Hou; Yiyu Song; Wenhu Xu; Yuxin Mao; Jianfeng Chen

doi:10.1007/s12195-023-00766-y

Contact Guidance Drives Upward Cellular Migration at the Mesoscopic Scale

Cell Mol Bioeng. 2023 May 1;16(3):205-218. doi: 10.1007/s12195-023-00766-y. eCollection 2023 Jun.

Authors

Xiaoxiao Chen^{1

2}, Youjun Xia^{2

3}, Wenqiang Du⁴, Han Liu¹, Ran Hou¹, Yiyu Song¹, Wenhu Xu¹, Yuxin Mao⁵, Jianfeng Chen¹

Affiliations

¹ School of Advanced Manufacturing, Nanchang University, Nanchang, 330031 Jiangxi China.
² Department of Precision Machinery and Precision Instrumentation, University of Science and Technology of China, Hefei, 230027 Anhui China.
³ Key Laboratory of Precision Scientific Instrumentation of Anhui Higher Education Institutes, University of Science and Technology of China, Hefei, 230027 Anhui China.
⁴ Biomedical Engineering Department, University of Connecticut Health Center, Farmington, CT 06030 USA.
⁵ School of Biomedical Engineering, Anhui Medical University, Hefei, 230032 Anhui China.

PMID: 37456789
PMCID: PMC10338420 (available on 2024-05-01)
DOI: 10.1007/s12195-023-00766-y

Abstract

Introduction: Cancer metastasis is associated with increased cancer incidence, recurrence, and mortality. The role of cell contact guidance behaviors in cancer metastasis has been recognized but has not been elucidated yet.

Methods: The contact guidance behavior of cancer cells in response to topographical constraints is identified using microgrooved substrates with varying dimensions at the mesoscopic scale. Then, the cell morphology is determined to quantitatively analyze the effects of substrate dimensions on cells contact guidance. Cell density and migrate velocity signatures within the cellular population are determined using time-lapse phase-contrast microscopy. The effect of soluble factors concentration is determined by culturing cells upside down. Then, the effect of cell-substrate interaction on cell migration is investigated using traction force microscopy.

Results: With increasing depth and decreasing groove width, cell elongation and alignment are enhanced, while cell spreading is inhibited. Moreover, cells display preferential distribution on the ridges, which is found to be more pronounced with increasing depth and groove width. Determinations of cell density and migration velocity signatures reveal that the preferential distribution on ridges is caused by cell upward migration. Combined with traction force measurement, we find that migration toward ridges is governed by different cell-substrate interactions between grooves and ridges caused by geometrical constraints. Interestingly, the upward migration of cells at the mesoscopic scale is driven by entropic maximization.

Conclusions: The mesoscopic cell contact guidance mechanism based on the entropic force driven theory provides basic support for the study of cell alignment and migration along healthy tissues with varying size, thereby aiding in the prediction of cancer metastasis.

Supplementary information: The online version contains supplementary material available at 10.1007/s12195-023-00766-y.

Keywords: Cell migration; Cell-substrate adhesion; Contact guidance; Mesoscopic scale; Topographical features.

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