SCHEEPDOG: Programming Electric Cues to Dynamically Herd Large-Scale Cell Migration.

Tom J Zajdel,Alejandro Rossello-Martinez,Linus Wang,Daniel J Cohen,Gawoon Shim

doi:10.1016/j.cels.2020.05.009

Tom J Zajdel, Alejandro Rossello-Martinez + Show 3 more

Open Access

https://doi.org/10.1016/j.cels.2020.05.009

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Journal: Cell Systems	Publication Date: Jun 1, 2020
Citations: 55	License type: cc-by

Affiliation: Princeton University, Imperial College London

Abstract

Directed cell migration is critical across biological processes spanning healing to cancer invasion, yet no existing tools allow real-time interactive guidance over such migration. We present a new bioreactor that harnesses electrotaxis-directed cell migration along electric field gradients-by integrating four independent electrodes under computer control to dynamically program electric field patterns, and hence steer cell migration. Using this platform, we programmed and characterized multiple precise, two-dimensional collective migration maneuvers in renal epithelia and primary skin keratinocyte ensembles. First, we demonstrated on-demand, 90-degree collective turning. Next, we developed a universal electrical stimulation scheme capable of programming arbitrary 2D migration maneuvers such as precise angular turns and migration in a complete circle. Our stimulation scheme proves that cells effectively time-average electric field cues, helping to elucidate the transduction timescales in electrotaxis. Together, this work represents an enabling platform for controlling cell migration with broad utility across many cell types.

Highlights

As directed and large-scale collective cell migration underlie key multicellular processes spanning morphogenesis, healing, and cancer progression, a tool to shepherd such migration would enable new possibilities across cell biology and biomedical engineering (Friedl and Gilmour, 2009)
We present the only instance of freely programmable, 2D herding of collective cell migration, enabled by our next-gen electro-bioreactor called SCHEEPDOG (Spatiotemporal Cellular HErding with Electrochemical Potentials to Dynamically Orient Galvanotaxis)
The bioreactor housing uses rapid, in situ microfluidic assembly around pre-patterned cells or tissues, and integrates bestpractices from our prior work and that of others (Cohen et al, 2014; Sun, 2017; Cho et al, 2018) (Figure 1 and S1). It ensures stability and consistency by reducing variable conditions in previous assembly procedures of microfluidic devices, many of which rely on vacuum grease and glass coverslip-ceilings (Cao et al, 2011; Gokoffski et al, 2019)

Summary

Introduction

As directed and large-scale collective cell migration underlie key multicellular processes spanning morphogenesis, healing, and cancer progression, a tool to shepherd such migration would enable new possibilities across cell biology and biomedical engineering (Friedl and Gilmour, 2009). Such a tool must be: (1) broadly applicable across multiple cell and tissue types and (2) programmable to allow spatiotemporal control. Chemotaxis, an obvious candidate, lacks broad applicability as it requires ligand-receptor interactions. Optogenetics requires genetic modification and must be targeted to individual cells at a subcellular level to guide migration (Weitzman and Hahn, 2014)

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