Galvanotactic control of collective cell migration in epithelial monolayers

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.

Electric signals regulate directional migration of ventral midbrain derived dopaminergic neural progenitor cells via Wnt/GSK3β signaling

“…These diverse responses indicate that the cellular effects of EFs are cell type and species specific, and need to be analyzed on a case-by-case basis. It has recently been demonstrated that collective migration of epithelium can be interactively guided by applied electric fields that bias the underlying signaling networks, because the regulation efficiency of cell migration is dependent on the size and shape of the cell population (Cohen et al, 2014). This contrasts with our observation when different experimental conditions are applied (unpublished data).…”

Impedance sensing device enables early detection of pressure ulcers in vivo

“…With a slight change in instrumentation, the same device can also be used to measure voltage at each electrode with respect to a common reference, creating a map of the voltage and endogenous electric field across the wound. It is well known that cells can be directed to migrate with an applied electric field [32][33][34][35][36] , and there is evidence, although somewhat controversial, that applying an electric field may assist in the healing process 37 . The device demonstrated here provides the capability to test the extension of these theories from cells to complex tissues in vivo.…”

Collective cell migration: guidance principles and hierarchies

“…In addition, migration-inducing cell surface receptors, including epidermal growth factor receptor (EGFR), acetylcholine receptor (AchR), and integrins were reported to respond electric fields and locally activate PI3K/Akt and MAP/ERK signaling [99,101]. In epithelial sheets, electrotaxis appears to engage both leader and follower cells to generate oriented traction forces parallel with the electric field and adaptive reorientation with altered field polarity [100,103].…”

“…Migration of an epithelial monolayer that is closing a tissue defect follows the interface between the underlying substrate and cell-free space until the gap is closed and contact inhibition of migration overrules promigratory signaling [11,30]. However, on additional exposure to an electric field, electrotaxis overrides other guidance principles resulting in either monolayers moving according to the current flow and in the opposite direction to open space or cells piling up at a barrier due to a lack of contact inhibition of migration [102,103]. Similarly, endothelial cells following a haptotactic gradient initiate migration in the opposite direction when exposed to countercurrent and sufficiently strong fluid flow, whereas haptotaxis dominates at low levels of shear stress [78].…”