Chair of Macromolecular Chemistry, Faculty of Natural Science II, Von-Danckelmann-Platz 4, Institute of Chemistry, Martin-Luther University Halle-Wittenberg, Halle (Saale), D-06120, Germany.
Biocenter, Martin-Luther University Halle-Wittenberg, Weinbergweg 22, Halle (Saale), D-06120, Germany.
Macromol Rapid Commun. 2021 Jun;42(12):e2100120. doi: 10.1002/marc.202100120. Epub 2021 May 13.
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. The impact of these conjugates on Aβ 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 Aβ . Other hydrophobic end groups are also delaying fibrillation of Aβ , 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.
近年来，已有研究报道细胞膜成分（如淀粉样β（Aβ）纤维中的脂质部分）在 Aβ 纤维形成中的成核作用。本文报道了由脂质锚（胆固醇、二酰基甘油）和亲水聚合物制成的缀合物对 Aβ 纤维形成的影响，旨在了解聚合物浊点温度（T）及其疏水尾部对淀粉样纤维形成的影响。新型脂质-聚合物缀合物由聚（低聚（乙二醇）丙烯酸酯）和疏水基团（二酰基甘油基、胆固醇基、辛基、癸基、十六烷基）作为锚通过可逆加成-断裂链转移（RAFT）聚合合成，允许通过改变侧链中的聚合度（n）和乙二醇单元数（m）来调整缀合物的亲-疏水性分布。通过体外动力学研究和透射电子显微镜（TEM）研究了这些缀合物对 Aβ 纤维形成的影响。疏水脂质锚显著延迟了纤维的形成（滞后时间和半时间都延长），与天然 Aβ 相比，通过 TEM 观察到相似的纤维结构。其他疏水末端基团也延迟了 Aβ 的纤维形成，这与它们的“n”和“m”无关，而更亲水的聚合物（侧链的乙二醇单元更长，辛基、癸基的 m = 3，胆固醇的 m = 5）仅略微抑制纤维形成。
