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Galvanotactic control of collective cell migration in epithelial monolayers

Nature Materials volume 13, pages 409–417 (2014)Cite this article

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A Corrigendum to this article was published on 22 April 2014

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Abstract

Many normal and pathological biological processes involve the migration of epithelial cell sheets. This arises from complex emergent behaviour resulting from the interplay between cellular signalling networks and the forces that physically couple the cells. Here, we demonstrate that collective migration of an epithelium can be interactively guided by applying electric fields that bias the underlying signalling networks. We show that complex, spatiotemporal cues are locally interpreted by the epithelium, resulting in rapid, coordinated responses such as a collective U-turn, divergent migration, and unchecked migration against an obstacle. We observed that the degree of external control depends on the size and shape of the cell population, and on the existence of physical coupling between cells. Together, our results offer design and engineering principles for the rational manipulation of the collective behaviour and material properties of a tissue.

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Figure 1: Galvanotactic chamber design.
Figure 2: Epithelial monolayers undergoing galvanotaxis perform collective U-turns and respond rapidly.
Figure 3: Epithelial monolayer migration follows field lines in 2D electric fields.
Figure 4: Monolayer size and shape affect galvanotactic controllability.
Figure 5: Leader cells are insensitive to galvanotaxis.
Figure 6: MDCK-II monolayers undergo galvanotaxis against co-cultured obstacles.

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Change history

  • 21 March 2014

    In the version of this Article originally published, in Figs 4a,e, 5b,c and 6a, the units for velocity should have read 'μm h–1'. This error has now been corrected in the online versions of the Article.

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Acknowledgements

We thank the following for reagents and advice: N. Borghi (Institut Jacques Monod, Paris); K. Matlin (Univ. Chicago); D.J. Seo (UC Berkeley); M. Lowndes (Stanford University); C. Tropini (Stanford University); W. Marshall (UCSF); S. Prabhu (UCLA) and J. Bone (UC Berkeley). This work was supported by a Graduate Fellowship from the NSF to D.J.C., HFSP (RGP0040/2012) to W.J.N., and EFRI-1240380 to M.M.M.

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Authors and Affiliations

  1. Joint Graduate Program in Bioengineering, University of California at Berkeley, Berkeley, California 94720, USA

    Daniel J. Cohen

  2. Department of Biology and Molelcular and Cellular Physiology, Stanford University, Stanford, California 94305, USA

    W. James Nelson

  3. Department of Electrical Engineering and Computer Science, University of California at Berkeley, Berkeley, California 94720, USA

    Michel M. Maharbiz

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  1. Daniel J. Cohen
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Contributions

D.J.C. designed and built the device, designed and performed experiments, and analysed and interpreted data. W.J.N. interpreted biological data. M.M.M. contributed to the design of the device. All authors participated in writing the paper.

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Correspondence to Daniel J. Cohen.

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The authors declare no competing financial interests.

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Cohen, D., James Nelson, W. & Maharbiz, M. Galvanotactic control of collective cell migration in epithelial monolayers. Nature Mater 13, 409–417 (2014). https://doi.org/10.1038/nmat3891

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