Nanoparticles Interacting with Proteins and Cells: A Systematic Study of Protein Surface Charge Effects

Abstract

Despite intense research on biological and biomedical applications of nanoparticles, our understanding of their basic interactions with the biological environment is still incomplete. Systematic variation of the physicochemical properties of the nanoparticles is widely seen as a promising strategy to obtain further insights. In view of the key role of the protein adsorption layer forming on nanoparticles in contact with biofluids, we systematically varied the surface charge of proteins adsorbing onto nanoparticles by chemical modification so as to examine the effect of Coulomb forces in modulating nano‐bio interactions. We chose human serum albumin (HSA) as a model protein and ultra‐small, negatively charged fluorescent gold nanoclusters (AuNCs) as model nanoparticles. By using fluorescence and CD spectroscopies, we measured binding affinities and structural changes upon binding of the HSA variants. The strengths of the protein‐nanoparticle interactions were found to change substantially upon modifying the surface charge of HSA. Furthermore, by using inductively coupled plasma optical emission spectroscopy, confocal fluorescence microscopy, scanning transmission electron microscopy and cell viability assays, we observed that cellular interactions of the AuNCs, including their adherence to cell membranes, uptake efficiency and cytotoxicity, depended markedly on the different surface charges of the HSA variants adsorbed onto the nanoparticles. These results illustrate vividly that the cellular responses to nanoparticle exposure depend on the specific properties of the proteins that adsorb onto nanoparticles from biofluids.

In vitro comparative cytotoxicity study of aminated polystyrene, zinc oxide and silver nanoparticles on a cervical cancer cell line

“…Due to the vast differences in their physico-chemical properties, primarily resultant from their differing synthesis methods, they are known to induce adverse effects in biological systems. NPs can interfere with cellular systems by the NPs interaction's with proteins, DNA, lipids, membrane, organelles, and biological fluids (Roiter et al 2008, Shang et al 2014, Khan et al 2015. Due to their reduced size (1-100 nm) and large surface area to volume ratio, they can easily cross cell membranes (Khan et al 2015) and further enter the bloodstream reaching different organs (Vishwakarma et al 2010).…”

Modulatory Effect of Citrate Reduced Gold and Biosynthesized Silver Nanoparticles on α-Amylase Activity

“…The binding of albumin protein on the surfaces of silver and gold nanoparticles has been studied for surface adhesion by researchers to understand the effect on its structural changes [32,33]. Biointeraction studies with AgNPs and protein and its SPR effect, surface charge effect was studied for various applications in biological sciences by various researchers [34,35].…”

Effects of surface charges of gold nanoclusters on long-term in vivo biodistribution, toxicity, and cancer radiation therapy

“…[32][33][34] Surface charge can affect adhesion to cell membranes as well as uptake efficiency. 35 Positively charged NPs bind strongly to serum components in the blood via noncovalent interactions with proteins and electrostatic interactions with the cell surface. [36][37][38] Furthermore, these positively charged NPs can be easily taken up by nonphagocytic cells and cause more disruption of the membrane integrity and lysosomal and mitochondrial damage than their negatively charged counterparts.…”