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Membrane mechanics as a probe of ion-channel gating mechanisms

Reeves, Daniel and Ursell, Tristan and Sens, Pierre and Kondev, Jane and Phillips, Rob (2008) Membrane mechanics as a probe of ion-channel gating mechanisms. Physical Review E, 78 (4). Art. No. 041901. ISSN 1539-3755. http://resolver.caltech.edu/CaltechAUTHORS:REEpre08

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Abstract

The details of conformational changes undergone by transmembrane ion channels in response to stimuli, such as electric fields and membrane tension, remain controversial. We approach this problem by considering how the conformational changes impose deformations in the lipid bilayer. We focus on the role of bilayer deformations in the context of voltage-gated channels because we hypothesize that such deformations are relevant in this case as well as for channels that are explicitly mechanosensitive. As a result of protein conformational changes, we predict that the lipid bilayer suffers deformations with a characteristic free-energy scale of 10kBT. This free energy is comparable to the voltage-dependent part of the total gating energy, and we argue that these deformations could play an important role in the overall free-energy budget of gating. As a result, channel activity will depend upon mechanical membrane parameters such as tension and leaflet thickness. We further argue that the membrane deformation around any channel can be divided into three generic classes of deformation that exhibit different mechanosensitive properties. Finally, we provide the theoretical framework that relates conformational changes during gating to tension and leaflet thickness dependence in the critical gating voltage. This line of investigation suggests experiments that could discern the dominant deformation imposed upon the membrane as a result of channel gating, thus providing clues as to the channel deformation induced by the stimulus.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1103/PhysRevE.78.041901DOIUNSPECIFIED
http://link.aps.org/abstract/PRE/v78/e041901PublisherUNSPECIFIED
Additional Information:©2008 The American Physical Society. (Received 10 May 2008; published 1 October 2008) We are thankful to a number of people for helpful conversation and comments on the manuscript: Chris Miller, Olaf Anderson, Cathy Morris, and Chris Gandhi. J.K. acknowledges the support of National Science Foundation Grants No. DMR-0403997 and No. DMR-0706458. R.P. acknowledges the support of National Science Foundation Grant No. CMS-0301657. T.U. and R.P. acknowledge the support of the National Science Foundation as well as the National Institutes of Health. D.R. acknowledges the support of National Science Foundation Grant No. DGE-0549390.
Funders:
Funding AgencyGrant Number
National Science FoundationDMR-0403997
National Science FoundationDMR-0706458
National Science FoundationCMS-0301657
National Institutes of HealthUNSPECIFIED
National Science FoundationDGE-0549390
Subject Keywords:bioelectric phenomena; biomechanics; biomembrane transport; deformation; lipid bilayers; molecular biophysics; proteins
Record Number:CaltechAUTHORS:REEpre08
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:REEpre08
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:11836
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:04 Oct 2008 04:12
Last Modified:26 Dec 2012 10:21

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