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Title: Protein crowding and lipid complexity influence the nanoscale dynamic organization of ion channels in cell membranes

Cell membranes are crowded and complex environments. To investigate the effect of protein-lipid interactions on dynamic organization in mammalian cell membranes, we have performed coarse-grained molecular dynamics simulations containing >100 copies of an inwardly rectifying potassium (Kir) channel which forms specific interactions with the regulatory lipid phosphatidylinositol 4,5-bisphosphate (PIP 2). The tendency of protein molecules to cluster has the effect of organizing the membrane into dynamic compartments. At the same time, the diversity of lipids present has a marked effect on the clustering behavior of ion channels. Sub-diffusion of proteins and lipids is observed. Protein crowding alters the sub-diffusive behavior of proteins and lipids such as PIP 2 which interact tightly with Kir channels. Protein crowding also affects bilayer properties, such as membrane undulations and bending rigidity, in a PIP 2-dependent manner. As a result, this interplay between the diffusion and the dynamic organization of Kir channels may have important implications for channel function.
Authors:
 [1] ; ORCiD logo [2] ;  [3] ;  [4] ; ORCiD logo [1] ;  [5] ; ORCiD logo [1]
  1. Univ. of Oxford, Oxford (United Kingdom)
  2. Univ. of Oxford, Oxford (United Kingdom); Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  3. Univ. of Oxford, Oxford (United Kingdom); D. E. Shaw Research, New York, NY (United States)
  4. Univ. of Oxford, Oxford (United Kingdom); Semmle, Oxford (United Kingdom)
  5. Univ. of Oxford, Oxford (United Kingdom); IPBS-CNRS, Midi-Pyrenees (France)
Publication Date:
Report Number(s):
LA-UR-17-25048
Journal ID: ISSN 2045-2322
Grant/Contract Number:
AC52-06NA25396
Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 7; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Research Org:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org:
Foreign Funding; USDOE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Biological Science; membrane proteins; clustering; molecular dynamics; mesoscale; single particle tracking
OSTI Identifier:
1422920

Duncan, Anna L., Reddy, Tyler John Edward, Koldsø, Heidi, Hélie, Jean, Fowler, Philip W., Chavent, Matthieu, and Sansom, Mark S. P.. Protein crowding and lipid complexity influence the nanoscale dynamic organization of ion channels in cell membranes. United States: N. p., Web. doi:10.1038/s41598-017-16865-6.
Duncan, Anna L., Reddy, Tyler John Edward, Koldsø, Heidi, Hélie, Jean, Fowler, Philip W., Chavent, Matthieu, & Sansom, Mark S. P.. Protein crowding and lipid complexity influence the nanoscale dynamic organization of ion channels in cell membranes. United States. doi:10.1038/s41598-017-16865-6.
Duncan, Anna L., Reddy, Tyler John Edward, Koldsø, Heidi, Hélie, Jean, Fowler, Philip W., Chavent, Matthieu, and Sansom, Mark S. P.. 2017. "Protein crowding and lipid complexity influence the nanoscale dynamic organization of ion channels in cell membranes". United States. doi:10.1038/s41598-017-16865-6. https://www.osti.gov/servlets/purl/1422920.
@article{osti_1422920,
title = {Protein crowding and lipid complexity influence the nanoscale dynamic organization of ion channels in cell membranes},
author = {Duncan, Anna L. and Reddy, Tyler John Edward and Koldsø, Heidi and Hélie, Jean and Fowler, Philip W. and Chavent, Matthieu and Sansom, Mark S. P.},
abstractNote = {Cell membranes are crowded and complex environments. To investigate the effect of protein-lipid interactions on dynamic organization in mammalian cell membranes, we have performed coarse-grained molecular dynamics simulations containing >100 copies of an inwardly rectifying potassium (Kir) channel which forms specific interactions with the regulatory lipid phosphatidylinositol 4,5-bisphosphate (PIP2). The tendency of protein molecules to cluster has the effect of organizing the membrane into dynamic compartments. At the same time, the diversity of lipids present has a marked effect on the clustering behavior of ion channels. Sub-diffusion of proteins and lipids is observed. Protein crowding alters the sub-diffusive behavior of proteins and lipids such as PIP2 which interact tightly with Kir channels. Protein crowding also affects bilayer properties, such as membrane undulations and bending rigidity, in a PIP2-dependent manner. As a result, this interplay between the diffusion and the dynamic organization of Kir channels may have important implications for channel function.},
doi = {10.1038/s41598-017-16865-6},
journal = {Scientific Reports},
number = 1,
volume = 7,
place = {United States},
year = {2017},
month = {11}
}