Membrane Anchored Polymers Modulate Amyloid Fibrillation. Issue 12 (13th May 2021)

• Record Type: Journal Article
• Authors: Sen, Newton; Hause, Gerd; Binder, Wolfgang H.
• Is Part Of: Macromolecular rapid communications. Volume 42:Issue 12(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-05-13
• Subjects: amyloid beta fibrillation -- lipid‐polymer conjugate -- stimuli‐responsive polymers; Macromolecules -- Periodicals; Polymers -- Periodicals; Chemistry -- Periodicals; 547.705
• DOI: 10.1002/marc.202100120
• Languages: English
• ISSNs: 1022-1336

Abstract

Abstract: The nucleating role of cellular membrane components, such as lipid moieties on amyloid beta (A β 1–40 ) fibrillation, has been reported in recent years. The influence of conjugates fabricated from lipid anchors (cholesterol, diacylglycerol) and hydrophilic polymers on A β 1–40 fibrillation is reported here, aiming to understand the impact of polymers cloud point temperature ( T cp ) and its hydrophobic tails on the amyloid fibrillation. Novel lipid‐polymer conjugates, consisting of poly(oligo(ethylene glycol) m 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. The impact of these conjugates on A β 1–40 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 A β 1–40 . Other hydrophobic end groups are also delaying fibrillation of A β 1–40, 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. Abstract : Hydrophobic interactions guide the assembly of soluble amyloid beta (A β 1–40 ) peptides into aggregates, with membrane lipids (cholesterol, diacylglycerols) being important contributors. Lipid conjugates of thermoresponsive poly(oligo(ethylene glycol) m acrylates) are prepared to mimic lipid interactions during A β 1–40 aggregation. Such, membrane‐similar conjugates inhibit A β 1–40 fibrillation, successfully elongating lag ( t lag ) and half times ( t 1/2 ) of the A β 1–40 peptides.