Hetero-oligomers in solution and binding to the raft membrane

Disruptions of cell membranes by tau and amylin oligomers are linked to Alzheimer's and Type 2 diabetics, respectively. Recent studies suggest that misfolded tau and amylin can form neurotoxic hetero-tau-amylin oligomers that are structurally different from the homo-oligomers. We have designed and created hetero-tau-amylin oligomers of different sizes using microsecond-resolved coarse-grained MD simulations. In addition, we have modeled the protein binding events of these hetero-oligomers to phase-separated lipid nanodomains (CO-raft) containing saturated phosphatidylcholine (PC), unsaturated PC, and cholesterol. The CO-raft contains the saturated PC- and cholesterol-enriched Lo domain, the unsaturated PC- and cholesterol-depleted Ld domain, and the boundary Lod domain. By adding an anionic lipid, phosphatidylserine (PS) or ganglioside (GM1), to one lipid leaflet of the CO-raft, an asymmetric PS-raft or GM-raft was also created. The PS- and GM1-clusters on the asymmetric PS- and GM-...