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

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