During development and disease, cells migrate collectively in response to gradients in physical, chemical and electrical cues. Despite its physiological significance and potential therapeutic applications, electrotactic collective cell movement is relatively less well understood. Here, we analyze the combined effect of intercellular interactions and electric fields on the directional migration of non-transformed mammary epithelial cells, MCF-10A. Our data show that clustered cells exhibit greater sensitivity to applied electric fields but align more slowly than isolated cells. Clustered cells achieve half-maximal directedness with an electric field that is 50% weaker than that required by isolated cells; however, clustered cells take ~2–4 fold longer to align. This trade-off in greater sensitivity and slower dynamics correlates with the slower speed and intrinsic directedness of collective movement even in the absence of an electric field. Whereas isolated cells exhibit a persistent random walk, the trajectories of clustered cells are more ballistic as evidenced by the superlinear dependence of their mean square displacement on time. Thus, intrinsically-directed, slower clustered cells take longer to redirect and align with an electric field. These findings help to define the operating space and the engineering trade-offs for using electric fields to affect cell movement in biomedical applications.
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We thank the members of the Asthagiri group for helpful discussions. This work was supported by the National Institutes of Health grant R01CA138899 and start-up resources provided by Northeastern University.
Conflict of interest
Mark L. Lalli and Anand R. Asthagiri declare that they have no conflict of interest.
No human or animal studies were carried out by the authors for this article.
Associate Editor Jason M. Haugh oversaw the review of this article.
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Lalli, M.L., Asthagiri, A.R. Collective Migration Exhibits Greater Sensitivity But Slower Dynamics of Alignment to Applied Electric Fields. Cel. Mol. Bioeng. 8, 247–257 (2015). https://doi.org/10.1007/s12195-015-0383-x
- Cell–cell interactions
- Directional bias