Resonance-driven ion transport and selectivity in prokaryotic ion channels

Ronald Westra*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Web of Science)

Abstract

Ion channels exhibit a remarkably high accuracy in selecting uniquely its associated type of ion. The mechanisms behind ion selectivity are not well understood. Current explanations build mainly on molecular biology and bioinformatics. Here we propose a simple physical model for ion selectivity based on the driven damped harmonic oscillator (DDHO). The driving force for this oscillator is provided by self-organizing harmonic turbulent structures in the dehydrating ionic flow through the ion channel, namely, oscillating pressure waves in one dimension, and toroidal vortices in two and three dimensions. Density fluctuations caused by these turbulences efficiently transmit their energy to aqua ions that resonate with the driving frequency. Consequently, these release their hydration shell and exit the ion channel as free ions. Existing modeling frameworks do not express the required complex spatiotemporal dynamics, hence we introduce a macroscopic continuum model for ionic dehydration and transport, based on the hydrodynamics of a dissipative ionic flow through an ion channel, subject to electrostatic and amphiphilic interactions. This model combines three classical physical fields: Navier-Stokes equations from hydrodynamics, Gauss's law from Maxwell theory, and the convection-diffusion equation from continuum physics. Numerical experiments with mixtures of chemical species of ions in various degrees of hydration indeed reveal the emergence of strong oscillations in the ionic flow that are instrumental in the efficient dehydration and cause a strong ionic jet into the cell. As such, they provide a powerful engine for the DDHO mechanism. Theoretical predictions of the modeling framework match significantly with empirical patch-clamp data. The DDHO standard response curve defines a unique resonance frequency that depends on the mass and charge of the ion. In this way, the driving oscillations act as a selection mechanism that filters out one specific ion. Application of the DDHO model to real ion data shows that this mechanism indeed clearly distinguishes between chemical species and between aqua and bare ions with a large Mahalanobis distance and high oscillator quality. The DDHO framework helps to understand how SNP mutations can cause severe genetic pathologies as they destroy the geometry of the channel and so alter the resonance peaks of the required ion type.

Original languageEnglish
Article number062410
Number of pages32
JournalPhysical Review E
Volume100
Issue number6
DOIs
Publication statusPublished - 23 Dec 2019

Keywords

  • MOLECULAR-DYNAMICS
  • POTASSIUM-CHANNEL
  • HYDROPHOBIC MOMENT
  • CONTINUUM-THEORIES
  • BROWNIAN DYNAMICS
  • ENTROPIC FORCES
  • KCSA CHANNEL
  • MECHANISM
  • HYDRATION
  • PERMEATION

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