Binding kinetics of ultrasmall gold nanoparticles with proteins

Autor(es)

Lira, Andre L. ^[1] ; Ferreira, Rodrigo S. ^[1] ; Torquato, Ricardo J. S. ^[1] ; Zhao, Huaying ^[2] ; Oliva, Maria Luiza V. ^[1] ; Hassan, Sergio A. ^[3] ; Schuck, Peter ^[2] ; Sousa, Alioscka A. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Biochem, Sao Paulo, SP - Brazil

^[2] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD - USA

^[3] NIH, Ctr Mol Modeling, OIR, CIT, Bldg 10, Bethesda, MD 20892 - USA

• Tipo de documento: Artigo Científico
• Fonte: NANOSCALE; v. 10, n. 7, p. 3235-3244, FEB 21 2018.
• Citações Web of Science: 8

Resumo

Synthetic ultrasmall nanoparticles (NPs) can be designed to interact with biologically active proteins in a controlled manner. However, the rational design of NPs requires a clear understanding of their interactions with proteins and the precise molecular mechanisms that lead to association/dissociation in biological media. Although much effort has been devoted to the study of the kinetics mechanism of 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 studied 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 found 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 found 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. (AU)

• Processo FAPESP: 13/18481-5 - Interações biológicas de uma biblioteca de nanopartículas de ouro com aplicações na nanomedicina
• Beneficiário: Alioscka Augusto Sousa
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores