On the effect of ligand shell heterogeneity on nanoparticle/protein binding thermodynamics.

Ahmet Bekdemir,Francesco Stellacci,Suiyang Liao

doi:10.1016/j.colsurfb.2018.11.027

Ahmet Bekdemir, Francesco Stellacci + Show 1 more

Open Access

https://doi.org/10.1016/j.colsurfb.2018.11.027

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Abstract

Nonspecific protein adhesion to nanoparticle (NP) has been proven to have important implications in nanomedicine. However, there are only a few examples of careful studies relating protein binding thermodynamics to NP physicochemical features. In particular, a systematic investigation of how NP/protein binding parameters scale with size for sub-10 nm NPs and whether this scaling is affected by the surface feature of NPs remain unaddressed. Previously, we have developed an analytical ultracentrifugation (AUC) based method to determine NP/protein binding thermodynamic parameters that was shown to be particularly effective for sub-10 nm NPs. In this work, we exclusively utilize this method to investigate the binding parameters for a well-defined set of gold NPs with varying size and surface ligand ratios to the model protein human serum albumin. We find that gold NPs with a homogenous distribution of hydrophilic molecules in their ligand shell have a monotonic dependence of their binding constants and of the maximum number of bound proteins as a function of their surface area. On the other hand, a more complex relation is found for particles with patchy ligand shell. The findings of this research highlight the significance of surface morphology on the interplay between protein binding behavior and NP size.

Highlights

The adsorption of proteins on nanomaterials upon contact in biological media, called protein corona, has been center of an increasing interest in nanomedicine and nanotoxicology [1,2,3]
Our results suggest a linearity between the surface area of hydrophilic gold NPs and their interaction with human serum albumin (HSA), indicated with KD and Nmax values
Using chloroform as the only solvent at 55 °C resulted in nanoparticles of approximately 3–4 nm core diameter, when the temperature was increased to 85 °C and a mixture of 1:1 chloroform:toluene was used, the reaction product were gold NPs approximately 5–6 nm in core diameter (Table 1)

Summary

Introduction

The adsorption of proteins on nanomaterials upon contact in biological media, called protein corona, has been center of an increasing interest in nanomedicine and nanotoxicology [1,2,3]. The degree of surface hydrophobicity of PNIPAM:BAM hybrid nanoparticles was shown to influence the binding stoichiometry at least for human serum albumin [16]. These studies were typically focused on hundreds of nanometer sized NPs where proteins see the surface of nanoparticle almost like a flat surface. We have shown that the phase separation of binary ligand mixtures on gold NPs into stripe-like domains [19,20] determines a number of interesting biological properties, including protein non-specific adsorption [21,22]. The question of how the presence of binary ligand mixture on the surface of sub-10 nm NPs affects the thermodynamic parameters in protein binding has not been addressed so far

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