Biointeractions of gold nanoparticles: influence of macromolecular crowding and soft interactions

• Grant number: 16/25535-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2017
• End date: June 30, 2020
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Alioscka Augusto Sousa
• Grantee: Rodrigo da Silva Ferreira
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The use of synthetic nanoparticles (NPs) in medical applications requires a detailed understanding of their interactions in biological media. On the one hand, nonspecific interactions with blood proteins can result in a number of adverse effects in vivo. On the other hand, NPs can be tailored to interact controllably with proteins and cells. NP-protein interactions in particular are traditionally studied in dilute buffer, whereas blood and the intracellular space contain a high concentration of biomolecules. In principle, this high molecular concentration could affect the biointeractions of NPs in several ways, such as: (i) promote NP aggregation; (ii) promote or hinder nonspecific NP-protein interactions; (iii) hinder the specific binding of functional NPs to their target proteins. Therefore, herein we propose to investigate the influence of volume exclusion and soft interactions on the biointeractions of NPs - both these effects arise from the high concentration of macromolecules in biological fluid. Ultrasmall gold nanoparticles will be used as a model NP system. In a first step, the interactions of the NPs with chymotrypsin will be characterized in buffer and concentrated solutions of osmolytes and polymers using a number of biophysical techniques. In a second step, we will investigate the influence of crowding and soft interactions on the association of functional NPs to a model target protein. We suggest that the non-specific effects of crowding and soft interactions must be taken into account in the characterization of nanomaterials in general. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LIRA, ANDRE L.; FERREIRA, RODRIGO S.; OLIVA, MARIA LUIZA, V; SOUSA, ALIOSCKA A.. Regulation of Thrombin Activity with Ultrasmall Nanoparticles: Effects of Surface Chemistry. Langmuir, v. 36, n. 27, p. 11-pg., 2020-07-14. (16/25535-2, 19/04372-6)

FERREIRA, RODRIGO S.; LIRA, ANDRE L.; TORQUATO, RICARDO J. S.; SCHUCK, PETER; SOUSA, ALIOSCKA A.. Mechanistic Insights into Ultrasmall Gold Nanoparticle-Protein Interactions through Measurement of Binding Kinetics. Journal of Physical Chemistry C, v. 123, n. 46, p. 28450-28459, NOV 21 2019. (19/04372-6, 16/25535-2)

FERREIRA, RODRIGO S.; LIRA, ANDRE L.; SOUSA, ALIOSCKA A.. Quantitative mechanistic model for ultrasmall nanoparticle-protein interactions. NANOSCALE, v. 12, n. 37, p. 19230-19240, OCT 7 2020. (19/04372-6, 16/25535-2)