颗粒物与蛋白质相互作用研究：吸附-脱附行为与淀粉样聚集

The interaction between particles and proteins is central to many aspects of environment and health fields. In this proposal, two types of proteins, mucoprotein and amyloid proteins, which are closely related with many serious diseases, are chosen as the models. The interaction between nanoparticles/ atmospheric particulates and proteins will be comprehensively investigated at the molecular and supramolecular level. Specifically, 1) we plan to study the adsorption-desorption behavior of particles on the mucoprotein surfaces and the effect of the deposited particles on the lubrication/antifouling performance of proteins. According to the change in proteins’ structure and the interaction force, together with the the theoretical calculation and simulation, we attempt to conclude the mechanism on the interaction between particles and proteins; 2) we plan to monitor the nucleation and fibrillation process of the amyloid proteins was monitored using a combination of electron microscopy and spectroscopic techniques. We also investigate the effect of particles with different characteristics on the aggregation behavior of amyloid proteins. Furthermore, we try to understand the mechanism of amyloid aggregation in the presence of particles; 3) we plan to develop the new approaches for enhancing the desorption of particles from protein surface, inhibiting the amyloid aggregation or inducing the disaggregation of amyloid fibrils, aiming to clear the toxicity of particles. The methodologies and results of this proposal will provide a useful reference for researchers who wish to in-depth understand the biological effect and the toxicity mechanism of particles.

颗粒物-蛋白质相互作用研究是环境与健康领域的前沿和难点之一。本项目以黏蛋白和淀粉样蛋白两类与重大疾病密切相关的蛋白质为研究对象，从分子、超分子尺度上研究纳米颗粒、大气颗粒物与蛋白质的相互作用。具体研究中：①考察颗粒物在黏蛋白表面的吸附-脱附行为及其对黏蛋白性能（润滑、抗污染）的影响，根据蛋白质结构、相互作用力大小等参数，结合理论计算模拟，剖析颗粒物-蛋白质相互作用机理；②组合光谱/波谱学、电镜学等，跟踪表征淀粉样蛋白的成核和纤维化过程，对比分析颗粒物对蛋白质聚集行为的影响，统计分析不同颗粒物特性对蛋白质聚集的影响规律，并剖析蛋白质聚集机理及颗粒物的影响机制；③开发颗粒物在黏蛋白表面的脱附过程强化、抑制蛋白质淀粉样聚集/诱导蛋白纤维解聚的新方法，消除颗粒物对蛋白的毒性影响。本项目的研究方法和成果可为深入理解颗粒物生物学效应及毒性机制提供有益的参考和丰富的实验依据。

颗粒物-蛋白质相互作用研究是环境与健康领域的前沿和难点之一。本项目以粘蛋白和淀粉样蛋白两类与重大疾病密切相关的蛋白质为研究对象，深入研究了纳米颗粒、大气颗粒物与蛋白质的相互作用。具体工作包括：1）揭示了黑磷量子点、二硫化物纳米片、飞灰颗粒物与粘蛋白的相互作用及其在粘蛋白表面的吸附-脱附行为，发现颗粒属性、表面修饰基团、pH值、离子强度/价态对表面吸脱附行为起重要作用。其中，黑磷量子点可在粘蛋白表面快速吸附并解脱，很难紧密附着在蛋白表面，经聚乙二醇修饰后吸附速率降低但吸附量增大；而飞灰颗粒物的引入，则与粘蛋白形成复合物（发生荧光淬灭），导致蛋白膜表面质量减少，表明飞灰颗粒物会破坏粘蛋白膜；2）发现聚苯乙烯纳塑料可通过吸附非极性或弱极性有机小分子污染物，促进淀粉样蛋白聚集核的形成，缩短聚集滞后时间，加快胰岛素淀粉样纤维化进程。分子动力学模拟结果揭示范德华力和疏水相互作用是促进蛋白聚集的主要作用力；3）设计合成了荧光硅纳米颗粒和黑磷量子点，有效抑制了淀粉样蛋白聚集，并可部分解聚淀粉样纤维。其中，黑磷量子点即使在超低浓度（100 ng/mL）下也具有出色的抑制胰岛素聚集和分解胰岛素成熟纤维的能力。黑磷量子点对胰岛素淀粉样纤维化的抑制作用体现在聚集的各个阶段，并可提高PC12细胞的存活率。分子动力学模拟表明黑磷量子点可稳定胰岛素原本的α-螺旋结构，并消除构成原纤维的β-折叠结构。综上，本项目的研究方法和成果可为深入理解颗粒物生物学效应及毒性机制提供有益的参考和丰富的实验依据。