Lipid-polymer hybrid-vesicles interrupt nucleation of amyloid fibrillation.

Solubility and aggregation of proteins are crucial factors for their functional and further biological roles. Aggregation of proteins , such as the amyloid beta (Aβ) peptide into fibrils, is significantly modulated by membrane lipids, abundantly present in cells. We developed a model membrane system, composed of lipid hybrid-vesicles bearing embedded hydrophilic polymers to study the aggregation of the Aβ peptide.

Inhibition of the Fibrillation of Amyloid Aβ by Hybrid-Lipid-Polymer Vesicles.

The transformation of functional proteins into amyloidic plaques is responsible for the impairment of neurological functions in patients fallen victim to debilitating neurological conditions like Alzheimer's, Parkinson's, and Huntington's diseases. The nucleating role of amyloid beta (Aβ ) peptide into amyloids is well established. Herein, lipid hybrid-vesicles are generated with glycerol/cholesterol-bearing polymers aiming to alter the nucleation process and modulate the early phases of Aβ fibrillation.

Membrane Anchored Polymers Modulate Amyloid Fibrillation.

The nucleating role of cellular membrane components, such as lipid moieties on amyloid beta (Aβ ) fibrillation, has been reported in recent years. The influence of conjugates fabricated from lipid anchors (cholesterol, diacylglycerol) and hydrophilic polymers on Aβ fibrillation is reported here, aiming to understand the impact of polymers cloud point temperature (T ) and its hydrophobic tails on the amyloid fibrillation. Novel lipid-polymer conjugates, consisting of poly(oligo(ethylene glycol) acrylates) and hydrophobic groups (diacylglyceryl-, cholesteryl-, octyl-, decyl-, hexadecyl-) as anchors are synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization, allowing to tune the hydrophilic-hydrophobic profile of the conjugates by varying both, the degree of polymerization (n) and number of ethylene glycol units (m) in their side chain.