Phospholipids Critical Micellar Concentrations Trigger Different Mechanisms of Intrinsically Disordered Proteins Interaction with Model Membranes
journal contributionposted on 2018-08-22, 00:00 authored by Federica Scollo, Carmelo Tempra, Fabio Lolicato, Michele F. M. Sciacca, Antonio Raudino, Danilo Milardi, Carmelo La Rosa
Amyloidogenic proteins are involved in many diseases, including Alzheimer’s, Parkinson’s, and type II diabetes. These proteins are thought to be toxic for cells because of their abnormal interaction with the cell membrane. Simpler model membranes (LUVs) have been used to study the early steps of membrane-protein interactions and their subsequent evolution. Phospholipid LUVs formed in water solution establish a chemical equilibrium between self-assembled LUVs and a small amount of phospholipids in water solution (CMC). Here, using both experimental and molecular dynamics simulations approach we demonstrate that the insertion of IAPP, an amyloidogenic peptide involved in diabetes, in membranes is driven by free lipids in solution in dynamic equilibrium with the self-assembled lipids of the bilayer. It is suggested that this could be a general mechanism lying at the root of membrane insertion processes of self-assembling peptides.
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LUVdynamics simulations approachIntrinsically Disordered Proteins InteractionCMCModel Membranes Amyloidogenic proteinsSimpler model membranesself-assembledpeptidePhospholipids Critical Micellar Concentrations TriggerIAPPtype II diabetesmembrane insertion processeswater solutioninteractionequilibrium