Electric Field Induced Wetting of a Hydrophobic Gate in a Model Nanopore Based on the 5-HT₃Receptor Channel

Abstract

In this study we examined the influence of a transmembrane voltage on the hydrophobic gating of nanopores using molecular dynamics simulations. We observed electric field induced wetting of a hydrophobic gate in a biologically inspired model nanopore based on the 5-HT3 receptor in its closed state, with a field of at least ∼100 mV nm −1 was required to hydrate the pore. We also found an unequal distribution of charged residues can generate an electric field intrinsic to the nanopore which, depending on its orientation, can alter the effect of the external field, thus making the wetting response asymmetric. This wetting response could be described by a simple model based on water surface tension, the volumetric energy contribution of the electric field, and the influence of charged amino acids lining the pore. Finally, the electric field response was used to determine time constants characterising the phase transitions of water confined within the nanopore, revealing liquid-vapour oscillations on a time scale of~5 ns. This time scale was largely independent of the water model employed and was similar for different sized pores representative of the open and closed states of the pore. Furthermore, our finding that the threshold voltage required for hydrating a hydrophobic gate depends on the orientation of the electric field provides an attractive perspective for the design of rectifying artificial nanopores. ToC/Abstract Graphic

Water in Nanopores and Biological Channels: A Molecular Simulation Perspective

“…The same 5-HT 3 pore has been used to explore electrowetting (see section 4.3 above), revealing that a (supra-physiological) potential difference of ∼0.85 V across the membrane was required to hydrate the hydrophobic gate of the closed (i.e., dewetted) state of the pore. 466 …”

Electrically Suppressed Outflow of Confined Liquid in Hydrophobic Nanopores

“…These localized features under electric fields are different from that in the electrowetting of hydrophobic membranes and channels. 43,44 To further probe the H-bond degradation, Figure 3c,d demonstrates the variation of local H-bond number density ρ HB with ε at different radial locations r/r 0 . The black dashed line separates the bulk region and interface region where the interface region is recognized by the outermost peak in the radial number density distribution (Figure S5).…”

“…This suppression agrees with the enhanced surface stress and the increase of the associated surface energy density by the electric field (Figures S6 and S7), which is similar to the electrowetting of hydrophobic membranes and channels. 43,44 Figure 3g shows the ensemble average of the H-bond orientation ⟨cos(θ HB-z )⟩, where θ HB-z is the angle formed by the nanopore axis and H-bonds and ranges between 0 and 90°. The insets present the cos(θ HB-z ) contours with axial and radial locations at ε = 0 (left) and 5% (right) and with E = 0 (top) and 0.3 V/nm (bottom).…”

An open state of a voltage-gated sodium channel involving a π-helix and conserved pore-facing asparagine

“…Having observed the experimental structure to be nonconducting at 0 mV, we further asked whether the application of a transmembrane potential might stimulate conformational transition to a hydrated, more plausibly open state. Indeed, the introduction of an electrical potential has been shown to alter the surface tension of water at hydrophobic surfaces and may result in the hydration of transmembrane pores via an electrowetting phenomenon (61,62). We therefore probed whether electrowetting might also enable hydration of NavMs.…”