Membrane Anchored Polymers Modulate Amyloid Fibrillation

Abstract

The nucleating role of cellular membrane components, such as lipid moieties on amyloid beta (Aβ1–40) fibrillation, has been reported in recent years. The influence of conjugates fabricated from lipid anchors (cholesterol, diacylglycerol) and hydrophilic polymers on Aβ1–40 fibrillation is reported here, aiming to understand the impact of polymers cloud point temperature (Tcp) and its hydrophobic tails on the amyloid fibrillation. Novel lipid-polymer conjugates, consisting of poly(oligo(ethylene glycol)macrylates) 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. The impact of these conjugates on Aβ1–40 fibrillation is investigated via in vitro kinetic studies and transmission electron microscopy (TEM). Hydrophobic lipid-anchors are significantly delaying fibrillation (both lag- and half times), observing similar fibrillar structures via TEM when compared to native Aβ1–40. Other hydrophobic end groups are also delaying fibrillation of Aβ1–40, irrespective of their “n” and “m,” whereas more hydrophilic polymers (both with longer ethylene glycol-sidechains, m = 3 for octyl, decyl and m = 5 for cholesterol) are only marginally inhibited fibrillation.