Glycocalyx bending by an electric field increases cell motility

Abstract

The application of physiological strength electric fields may produce a wide range of effects on cells. The mechanisms by which cells detect the presence of these fields, however, are not fully understood. Previous experiments have shown that directionality of cells in the field is governed by an electromechanical mechanism in which the field exerts a torque on the negatively charged, inner glycocalyx that is then transmitted as a force on the cytoskeleton. This mechanism is similar to that by which cells detect fluid shear forces. Several authors, however, have reported that cell directionality and motility behave differently in an electric field. We propose here a second electromechanical mechanism in which the field bends the negatively charged, outer glycocalyx in proximity to the substrate, increasing cell adhesion and, thus, cell motility. The increase in motility depends not only on the field strength, but also on the adhesion of the cell to the substrate prior to application of the field. We show that these mechanisms are common to both human cells and amoebae and, hence, are evolutionarily conserved. Furthermore, the mechanism for detection of electric fields is simply an extension of the mechanism for detecting fluid shears. Bioelectromagnetics. 38:482-493, 2017. © 2017 Wiley Periodicals, Inc.

The Application of Electric Fields in Biology and Medicine

“…The predictions of the electromechanical model are consistent with the galvanotaxis of keratinocytes [36] and amoeba [37]. Galvanotaxis serves as a convenient effect for comparing the three proposed mechanisms because it is a process that is readily reproduced and is easily measured in real time.…”

“…However, if the cell adhesion is already optimal, the field does not produce a significant additional motility increase. The addition of positively-charged calcium ions that bind to the negativelycharged glycocalyx reduced the increase in directionality and motility produced by the field on amoeba-providing further confirmation of the electromechanical model [37]. The details are presented below.…”

“…Further confirmation of the electromechanical model, which identifies the glycocalyx as the transduction site, has been provided by Finkelstein et al [47] who showed that removal of the major negatively charged molecules in the glycocalyx in 3 T3 and HeLa cells eliminated galvanotaxis. Moreover, the effect of the superimposed fields on cell motility (speed) is also explained by the model [37]. An increase in cell motility often, but not always, accompanies the increase in directionality toward the field.…”

“…We present here an abbreviated description of the research we have conducted [36,37] to determine the mechanism by which cells initially detect physiological strength electric fields. Identifying and understanding this mechanism is important for further developing the various applications described above.…”

“…Three mechanisms have been proposed for this initial transduction process: (1) electrodiffusion/osmosis [38,39], (2) opening of voltage-gated channels [40], and (3) electromechanical torque exerted on the glycocalyx [41]. The electrodiffusion/osmosis model requires fields that are stronger than typical physiological strength fields applied for relatively long time intervals, and the changes in transmembrane potential produced by such fields are insufficient to open voltage-gated channels [37].…”