Nucleation of protein fibrillation by nanoparticles
Nucleation of protein fibrillation by nanoparticles
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DOI：
10.1073/pnas.0701250104
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发表时间：
2007-05-22
影响因子：
11.1
通讯作者：
Dawson, Kenneth A.
中科院分区：
文献类型：
--
作者：
Linse, Sara;Cabaleiro-Lago, Celia;Dawson, Kenneth A.
纳米颗粒呈现巨大的表面积，并发现通过减少成核的滞后时间来提高蛋白质原纤化的速率。蛋白质纤维化涉及许多人类疾病，包括阿尔茨海默氏病、克-雅二氏病和透析相关淀粉样变性。原纤形成通过成核依赖性动力学发生，其中临界核的形成是关键的速率决定步骤，之后原纤化快速进行。我们发现，纳米粒子（共聚物颗粒，氧化铈颗粒，量子点，和碳纳米管）提高了一个关键的核的出现的概率，从人β（2）-微球蛋白的蛋白质纤维成核。观察到的较短的滞后（成核）阶段取决于颗粒表面的量和性质。在溶液和纳米颗粒表面之间存在蛋白质交换，并且β（2）-微球蛋白在颗粒表面上形成多层，提供促进寡聚体形成的局部增加的蛋白质浓度。这和缩短的滞后期表明，涉及表面辅助成核的机制，可能会增加毒性簇和淀粉样蛋白形成的风险。它还为蛋白质和肽的受控自组装成新型纳米材料的新途径打开了大门。
Nanoparticles present enormous surface areas and are found to enhance the rate of protein fibrillation by decreasing the lag time for nucleation. Protein fibrillation is involved in many human diseases, including Alzheimer's, Creutzfeld-Jacob disease, and dialysis-related amyloidosis. Fibril formation occurs by nucleation-dependent kinetics, wherein formation of a critical nucleus is the key rate-determining step, after which fibrillation proceeds rapidly. We show that nanoparticles (copolymer particles, cerium oxide particles, quantum dots, and carbon nanotubes) enhance the probability of appearance of a critical nucleus for nucleation of protein fibrils from human beta(2)-microglobulin. The observed shorter lag (nucleation) phase depends on the amount and nature of particle surface. There is an exchange of protein between solution and nanoparticle surface, and beta(2)-Microglobulin forms multiple layers on the particle surface, providing a locally increased protein concentration promoting oligomer formation. This and the shortened lag phase suggest a mechanism involving surf ace-assisted nucleation that may increase the risk for toxic cluster and amyloid formation. It also opens the door to new routes for the controlled self-assembly of proteins and peptides into novel nanomaterials.