A condensation-ordering mechanism in nanoparticle-catalyzed peptide aggregation.
A condensation-ordering mechanism in nanoparticle-catalyzed peptide aggregation.
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DOI：
10.1371/journal.pcbi.1000458
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发表时间：
2009-08
影响因子：
4.3
通讯作者：
Vendruscolo M
中科院分区：
文献类型：
--
作者：
Auer S;Trovato A;Vendruscolo M
在活细胞中引入纳米粒子能够强烈地促进多肽和蛋白质的聚集。我们在这里使用分子动力学模拟来详细描述纳米颗粒表面催化多肽自组装成纤维结构的过程。在毫秒时间尺度上对数百个多肽系统的模拟使我们能够证明聚集机制包括第一阶段，小结构无序的低聚物聚集在纳米颗粒上，第二阶段，随着它们的大小增加，它们进化成高度有序的。蛋白质错误折叠和聚集与多种人类疾病有关，包括阿尔茨海默病、帕金森病和晚发性糖尿病。最近已经认识到，聚集过程可能是由纳米颗粒的存在引发的。我们在这里使用分子动力学模拟来表征这种纳米颗粒能够提高肽聚集体形成速率的分子机制。我们的研究结果表明，纳米颗粒表面作为一种催化剂，增加了局部肽的浓度，从而促进了它们随后组装成稳定的纤维结构。我们提出的方法，除了提供纳米颗粒存在下多肽聚集过程的描述外，还将使研究生物体内存在的各种其他潜在的聚集促进剂的作用机制成为可能，包括脂质膜和其他细胞成分。
Nanoparticles introduced in living cells are capable of strongly promoting the aggregation of peptides and proteins. We use here molecular dynamics simulations to characterise in detail the process by which nanoparticle surfaces catalyse the self-assembly of peptides into fibrillar structures. The simulation of a system of hundreds of peptides over the millisecond timescale enables us to show that the mechanism of aggregation involves a first phase in which small structurally disordered oligomers assemble onto the nanoparticle and a second phase in which they evolve into highly ordered as their size increases. Protein misfolding and aggregation are associated with a wide variety of human disorders, which include Alzheimer's and Parkinson's diseases and late onset diabetes. It has been recently realised that the process of aggregation may be triggered by the presence of nanoparticles. We use here molecular dynamics simulations to characterise the molecular mechanism by which such nanoparticles are capable of enhancing the rate of formation of peptide aggregates. Our findings indicate that nanoparticle surfaces act as a catalyst that increases the local concentration of peptides, thus facilitating their subsequent assembly into stable fibrillar structures. The approach that we present, in addition to providing a description of the process of aggregation of peptides in the presence of nanoparticles, will enable the study of the mechanism of action of a variety of other potential aggregation-promoting agents present in living organisms, including lipid membranes and other cellular components.
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影响因子：
11.4
作者：
Fändrich, M;Dobson, CM
通讯作者：
Dobson, CM
DOI：
10.1073/pnas.0402525101
发表时间：
2004-05-25
影响因子：
11.1
作者：
Hoang, TX;Trovato, A;Maritan, A
通讯作者：
Maritan, A
影响因子：
--
作者：
Auer, Stefan;Dobson, Christopher M.;Vendruscolo, Michele
通讯作者：
Vendruscolo, Michele
影响因子：
4.4
作者：
Bellesia, Giovanni;Shea, Joan-Emma
通讯作者：
Shea, Joan-Emma
DOI：
10.1073/pnas.0708193105
发表时间：
2008-04-22
影响因子：
11.1
作者：
Baumketner, Andrij;Krone, Mary Griffin;Shea, Joan-Emma
通讯作者：
Shea, Joan-Emma