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Contact Guidance Drives Upward Cellular Migration at the Mesoscopic Scale

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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.

Graphical Abstract

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Acknowledgements

The authors also thank Ze Cai from Key Laboratory of Precision Scientific Instrumentation of Anhui Higher Education Institutes, University of Science and Technology of China; Ran Rao from CAS Key Laboratory of Mechanical Behavior and Design of Materials, Department of Modern Mechanics, University of Science and Technology of China, for their help with AFM measurement and observation of cellular motility using time-lapse phase-contrast microscopy.

Funding

This work was supported by the National Natural Science Foundation of China [No. 51905248].

Author information

Author notes

  1. Xiaoxiao Chen and Youjun Xia are co-first authors

Authors and Affiliations

  1. School of Advanced Manufacturing, Nanchang University, Nanchang, 330031, Jiangxi, China

    Xiaoxiao Chen, Han Liu, Ran Hou, Yiyu Song, Wenhu Xu & Jianfeng Chen

  2. Department of Precision Machinery and Precision Instrumentation, University of Science and Technology of China, Hefei, 230027, Anhui, China

    Xiaoxiao Chen & Youjun Xia

  3. Key Laboratory of Precision Scientific Instrumentation of Anhui Higher Education Institutes, University of Science and Technology of China, Hefei, 230027, Anhui, China

    Youjun Xia

  4. Biomedical Engineering Department, University of Connecticut Health Center, Farmington, CT, 06030, USA

    Wenqiang Du

  5. School of Biomedical Engineering, Anhui Medical University, Hefei, 230032, Anhui, China

    Yuxin Mao

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Contributions

XC, YX, WD, and JC contributed to the conception and design of the study. HL, RH, and YS performed the experiments and analyzed the data. WX and YM contributed to writing reviews and editing. XC contributed to the original draft writing. JC contributed to funding acquisition and review. All authors contributed to the manuscript revision, read, and approved the submitted version. All authors reviewed this manuscript, contributed, and approved the final manuscript.

Corresponding author

Correspondence to Jianfeng Chen.

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Conflict of interest

Xiaoxiao Chen, Youjun Xia, Wenqiang Du, Han Liu, Ran Hou, Yiyu Song, Wenhu Xu, Yuxin Mao and Jianfeng Chen declare that they have no conflict of interest.

Ethical Approval

No human or animal studies were carried out by the authors for this article.

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Associate Editor Anubhav Tripathi oversaw the review of this article.

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Chen, X., Xia, Y., Du, W. et al. Contact Guidance Drives Upward Cellular Migration at the Mesoscopic Scale. Cel. Mol. Bioeng. 16, 205–218 (2023). https://doi.org/10.1007/s12195-023-00766-y

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