Voltage Gating of a Biomimetic Nanopore: Electrowetting of a Hydrophobic Barrier

Jemma L Trick,Chen Song,Mark S P Sansom,E Jayne Wallace

doi:10.1021/acsnano.6b07865

Jemma L Trick, Chen Song + Show 2 more

Open Access

https://doi.org/10.1021/acsnano.6b07865

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Abstract

It is desirable that nanopores that are components of biosensors are gated, i.e., capable of controllable switching between closed (impermeable) and open (permeable) states. A central hydrophobic barrier within a nanopore may act as a voltage-dependent gate via electrowetting, i.e., changes in nanopore surface wettability by application of an electric field. We use "computational electrophysiology" simulations to demonstrate and characterize electrowetting of a biomimetic nanopore containing a hydrophobic gate. We show that a hydrophobic gate in a model β-barrel nanopore can be functionally opened by electrowetting at voltages that do not electroporate lipid bilayers. During the process of electrowetting, voltage-induced alignment of water dipoles occurs within the hydrophobic gate region of the nanopore, with water entry preceding permeation of ions through the opened nanopore. When the ionic imbalance that generates a transbilayer potential is dissipated, water is expelled from the hydrophobic gate and the nanopore recloses. The open nanopore formed by electrowetting of a "featureless" β-barrel is anionic selective due to the transmembrane dipole potential resulting from binding of Na+ ions to the headgroup regions of the surrounding lipid bilayer. Thus, hydrophobic barriers can provide voltage-dependent gates in designed biomimetic nanopores. This extends our understanding of hydrophobic gating in synthetic and biological nanopores, providing a framework for the design of functional nanopores with tailored gating functionality.

Highlights

A promising design of a potential gate in a nanopore is the presence of a hydrophobic barrier within the pore.[14]
Our model protein nanopores were derived from those designed in a previous study,[43] consisting of a membrane spanning a β-barrel with a central hydrophobic barrier formed by rings of leucine side chains
We have demonstrated, using realistic simulation of transbilayer voltages via computational electrophysiology, that hydrophobic gates in model β-barrel nanopores can be functionally opened by electrowetting at voltages that do not electroporate lipid bilayers (Figure 7)

Summary

Introduction

A promising design of a potential gate in a nanopore is the presence of a hydrophobic barrier within the pore.[14] Such a region may be sterically unoccluded but of sufficient local hydrophobicity to “dewet”, i.e., to exclude water molecules and prevent permeation of both water molecules and ions.[15] Such a hydrophobic region in a nanopore has been the subject of some interest and has been variously referred to as a hydrophobic gate,[16] barrier,[17] vapor lock,[18,19] or a hydrophobic region leading to local dewetting of a pore The properties of such hydrophobic barriers in nanopores and their dependence on local pore geometry, hydrophobicity, and flexibility have formed the subject of numerous computational studies of hydrophobic gates in simple models,[14,15,20−25] in nanopores formed by carbon nanotubes,[26−28] and in biological pores.[16,29−31] rather less attention has been paid to how such gates may be switched between closed and open states in a controlled fashion, even though this is of central importance in the design of functional nanopores for a number of applications. We use CE to demonstrate and characterize electrowetting of a biomimetic nanopore containing a hydrophobic gate, showing that this permits controllable and reversible voltage gating of a nanopore in a lipid bilayer membrane

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