The cellular membrane disruption induced by the aggregation of Aβ peptide has been proposed as a plausible cause of neuronal cell death during Alzheimer’s disease. The molecular-level details of the Aβ interaction with cellular membranes were previously probed using solid state NMR (ssNMR), however, due to the limited sensitivity of the latter, studies were limited to samples with high Aβ-to-lipid ratio.

The dynamic nuclear polarization (DNP) is a technique for increasing the sensitivity of NMR. In this work we demonstrate the feasibility of DNP-enhanced ssNMR studies of Aβ₄₀ peptide interacting with various model liposomes: (1) a mixture of zwitterionic 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) and negatively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (POPG); (2) a mixture of POPC, POPG, cholesterol, sphingomyelin and ganglioside GM1; (3) the synaptic plasma membrane vesicles (SPMVs) extracted from rat brain tissues. In addition, DNP-ssNMR was applied to capturing changes in Aβ₄₀ conformation taking place upon the peptide insertion into POPG liposomes. The signal enhancements under conditions of DNP allow carrying out informative 2D ssNMR experiments with about 0.25 mg of Aβ₄₀ peptides (i.e. reaching Aβ₄₀-to-lipid ratio of 1:200). In the studied liposome models, the ¹³C NMR chemical shifts at many ¹³C-labelled sites of Aβ₄₀ are characteristic of β-sheets. In addition, in POPG liposomes the peptide forms hydrophobic contacts F19-L34 and F19-I32. Both the chemical shifts and hydrophobic contacts of Aβ₄₀ in POPG remain the same before and after 8 h of incubation. This suggests that conformation at the ¹³C-labelled sites of the peptide is similar before and after the insertion process. Overall, our results demonstrate that DNP helps to overcome the sensitivity limitation of ssNMR, and thereby expand the applicability of ssNMR for charactering the Aβ peptide interacting with lipids.

已提出由 Aβ 肽聚集引起的细胞膜破坏是阿尔茨海默病期间神经元细胞死亡的一个可能原因。先前使用固态核磁共振 (ssNMR) 探测了 Aβ 与细胞膜相互作用的分子水平细节，然而，由于后者的灵敏度有限，研究仅限于具有高 Aβ 与脂质比率的样品。

动态核极化 (DNP) 是一种提高 NMR 灵敏度的技术。_{在这项工作中，我们证明了 Aβ 40}肽与各种模型脂质体相互作用的 DNP 增强 ssNMR 研究的可行性：(1) 两性离子 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) 和带负电荷的 1 的混合物-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (POPG)；(2)POPC、POPG、胆固醇、鞘磷脂和神经节苷脂GM1的混合物；(3)从大鼠脑组织中提取的突触质膜囊泡(SPMVs)。此外，DNP-ssNMR 用于捕获 Aβ _40的变化肽插入 POPG 脂质体时发生构象。DNP 条件下的信号增强允许使用约 0.25 mg Aβ ₄₀肽（即达到1:200 的Aβ _{40与脂质比率）进行信息丰富的 2D ssNMR 实验。}在研究的脂质体模型中，Aβ _40的许多^{13 C 标记位点的13} C NMR 化学位移是 β-折叠的特征。此外，在 POPG 脂质体中，肽形成疏水接触 F19-L34 和 F19-I32。_{POPG 中 Aβ 40}的化学位移和疏水接触在孵育 8 小时前后保持不变。这表明在¹³肽的 C 标记位点在插入过程之前和之后是相似的。总体而言，我们的结果表明，DNP 有助于克服 ssNMR 的灵敏度限制，从而扩大了 ssNMR 在表征 Aβ 肽与脂质相互作用方面的适用性。