Scollo Federica, Tempra Carmelo, Lolicato Fabio, Sciacca Michele F M, Raudino Antonio, Milardi Danilo, La Rosa Carmelo
Department of Chemical Sciences , University of Catania , Viale A. Doria 6 , 95125 Catania , Italy.
Department of Physics , University of Helsinki , P.O. Box 64, FI-00014 , Helsinki , Finland.
J Phys Chem Lett. 2018 Sep 6;9(17):5125-5129. doi: 10.1021/acs.jpclett.8b02241. Epub 2018 Aug 27.
Amyloidogenic proteins are involved in many diseases, including Alzheimer's, Parkinson's, and type II diabetes. These proteins are thought to be toxic for cells because of their abnormal interaction with the cell membrane. Simpler model membranes (LUVs) have been used to study the early steps of membrane-protein interactions and their subsequent evolution. Phospholipid LUVs formed in water solution establish a chemical equilibrium between self-assembled LUVs and a small amount of phospholipids in water solution (CMC). Here, using both experimental and molecular dynamics simulations approach we demonstrate that the insertion of IAPP, an amyloidogenic peptide involved in diabetes, in membranes is driven by free lipids in solution in dynamic equilibrium with the self-assembled lipids of the bilayer. It is suggested that this could be a general mechanism lying at the root of membrane insertion processes of self-assembling peptides.
淀粉样蛋白与许多疾病有关，包括阿尔茨海默病、帕金森病和II型糖尿病。这些蛋白质被认为对细胞有毒，因为它们与细胞膜存在异常相互作用。更简单的模型膜（大单层囊泡）已被用于研究膜 - 蛋白相互作用的早期步骤及其后续演变。在水溶液中形成的磷脂大单层囊泡在自组装的大单层囊泡和水溶液中的少量磷脂（临界胶束浓度）之间建立化学平衡。在这里，我们使用实验和分子动力学模拟方法证明，参与糖尿病的淀粉样肽胰岛淀粉样多肽（IAPP）在膜中的插入是由溶液中与双层自组装脂质处于动态平衡的游离脂质驱动的。有人提出，这可能是自组装肽膜插入过程的一个普遍机制。
