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

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Abstract

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.

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Duncan, A. L., Reddy, T., Koldsø, H., Hélie, J., Fowler, P. W., Chavent, M., & Sansom, M. S. P. (2017). Protein crowding and lipid complexity influence the nanoscale dynamic organization of ion channels in cell membranes. Scientific Reports, 7(1). https://doi.org/10.1038/s41598-017-16865-6

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