Binding kinetics of ultrasmall gold nanoparticles with proteins.
Binding kinetics of ultrasmall gold nanoparticles with proteins.
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DOI：
10.1039/c7nr06810g
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发表时间：
2018-02-15
期刊：
影响因子：
6.7
通讯作者：
Sousa AA
中科院分区：
文献类型：
--
作者：
Lira AL ;Ferreira RS ;Torquato RJS ;Zhao H ;Oliva MLV ;Hassan SA ;Schuck P ;Sousa AA
人工合成的超小纳米颗粒(NPs)可以设计成以受控的方式与具有生物活性的蛋白质相互作用。然而，合理设计纳米粒子需要清楚地了解它们与蛋白质的相互作用，以及在生物介质中导致缔合/解离的精确分子机制。虽然人们对蛋白质在大颗粒上形成电晕的动力学机制进行了大量的研究，但在超小颗粒上NP-蛋白质相互作用的性质是完全不同的，也很少被理解。采用实验和计算相结合的方法，我们研究了模型蛋白质CrataBL与经对硫代苯甲酸(AuMBA)和谷胱甘肽(AuGSH)钝化的超小金纳米颗粒的相互作用。我们已将该体系确定为了解结合亲和力和动力学对NP表面化学的依赖的理想体外平台。我们发现，钝化NP层的结构和化学复杂性导致了从缓慢和反应受限(AuGSH)到快速和扩散受限(AuMBA)的截然不同的缔合动力学。我们还发现，在缓冲溶液中测量到的AuGSH与蛋白质之间的弱相互作用和缓慢相互作用在大分子拥挤溶液中被增强。这些发现促进了我们对超小范围内仿生NP-蛋白质相互作用的机制的理解，并对在所有生物介质常见的拥挤条件下设计和使用NPs具有指导意义。纳米粒子与蛋白质相互作用的动力学受纳米粒子表面化学的调控。
Synthetic ultrasmall nanoparticles (NPs) can be designed to interact with biologically active proteins in a controlled manner. However, rational design of NPs requires a clear understanding of their interactions with proteins and the precise molecular mechanisms that leads to association/dissociation in biological media. Although much effort has been devoted to the study of the kinetics mechanism of the protein corona formation on large NPs, the nature of NP-protein interactions in the ultrasmall regime is radically different and poorly understood. Using a combination of experimental and computational approaches, we study the interactions of a model protein, CrataBL, with ultrasmall gold NPs passivated with p-mercaptobenzoic acid (AuMBA) and glutathione (AuGSH). We have identified this system as an ideal in vitro platform to understand the dependence of binding affinity and kinetics on NP surface chemistry. We find that the structural and chemical complexity of the passivating NP layer leads to quite different association kinetics, from slow and reaction-limited (AuGSH) to fast and diffusion-limited (AuMBA). We also find that the otherwise weak and slow AuGSH-protein interactions measured in buffer solution are enhanced in macromolecular crowded solutions. These findings advance our mechanistic understanding of biomimetic NP-protein interactions in the ultrasmall regime, and have implications for the design and use of NPs in the crowded conditions common to all biological media. The kinetics of nanoparticle-protein interactions is modulated by nanoparticle surface chemistry.
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影响因子：
3
作者：
Cardone, Antonio;Bornstein, Aaron;Pant, Harish C.;Brady, Mary;Sriram, Ram;Hassan, Sergio A.
通讯作者：
Hassan, Sergio A.
影响因子：
12.6
作者：
Canoa, Pilar;Simon-Vazquez, Rosana;Gonzalez-Fernandez, Africa
通讯作者：
Gonzalez-Fernandez, Africa
影响因子：
17.1
作者：
Casals, Eudald;Pfaller, Tobias;Puntes, Victor
通讯作者：
Puntes, Victor
影响因子：
17.1
作者：
Hassan SA
通讯作者：
Hassan SA
影响因子：
38.3
作者：
Deng, Zhou J.;Liang, Mingtao;Minchin, Rodney F.
通讯作者：
Minchin, Rodney F.