BRANCOLINI Giorgia Center S3, CNR-NANO, Institute of Nanoscience

Nanoparticles (NPs) are recognized to exhibit distinct physical and chemical properties compared with the same materials in the bulk form.[1] As they enter into biological systems, they are immediately exposed to a variety and concentration of proteins. The physico-chemical interactions between proteins and NPs are influenced by the surface chemistry of the NPs. The formation of protein-NPs complexes rather than the NPs alone, determines the resulting biological responses [2] which can affect protein function, such as fibrillogenesis. Protein fibrillation is common to many protein and it causes cerebral and systemic amyloid disease. To identify the effects of NP surface chemistry on the fibrillation propensity of proteins, the interactions between β 2 -microglobulin and citrate-capped gold nanoparticles (AuNPs) have been investigated (Fig. 1). The interaction with two amyloidogenic variants: (a) the truncated ΔN6 and (b) the mutated D76N is included in the study in order to propose a fibrillization pathway. Different interaction modes and proteins conformations have been studied by nuclear magnetic resonance [3] and simulations at multiple levels (Enhanced Molecular Dynamics and Brownian Dynamics) that cover multiple length- and timescales. [4] The results provide insights into the driving forces for the binding of β 2 -microglobulin proteins to citrate-capped AuNPs and the subsequent effects on the conformational changes of the proteins, which are crucial in the fibrillation process. [1] Kumar et al., 2013. Manual on Critical Issues in Nanotechnology R&D Management: An Asia-Pacific Perspective. APCTT-ESCAP [2] Lynch, I. et al., Adv. Colloid Interface Sci. 2007, 134-135, 167-174. [3] (i) Mangione, P. P. et al., J. Biol. Chem. 2013, 288, 30917-30930 (ii) G. Esposito et al. Subcell Biochem. 2012, 65, 165-83. [4] (i) Iori, F. et al. J. Comput. Chem. 2009, 30, 1465 (ii) Brancolini, G. et al. ACS Nano, 2012, 6, 9863. (iii) Brancolini, G. et al. Nanoscale, 2014, DOI: 10.1039/C4NR01514B