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

TY - JOUR

T1 - Protein crowding and lipid complexity influence the nanoscale dynamic organization of ion channels in cell membranes

AU - Duncan, Anna L.

AU - Reddy, Tyler

AU - Koldsø, Heidi

AU - Hélie, Jean

AU - Fowler, Philip W.

AU - Chavent, Matthieu

AU - Sansom, Mark S.P.

N1 - Publisher Copyright: © 2017 The Author(s).

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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. This interplay between the diffusion and the dynamic organization of Kir channels may have important implications for channel function.

AB - 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. This interplay between the diffusion and the dynamic organization of Kir channels may have important implications for channel function.

UR - http://www.scopus.com/inward/record.url?scp=85036606055&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-16865-6

DO - 10.1038/s41598-017-16865-6

M3 - Journal article

C2 - 29192147

AN - SCOPUS:85036606055

SN - 2045-2322

VL - 7

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 16647

ER -