Molecular Interaction of Poly(acrylic acid) Gold Nanoparticles with Human Fibrinogen

Abstract

The binding of fibrinogen to various nanoparticles can result in protein unfolding and exposure of cryptic epitopes that subsequently interact with cell surface receptors. This response is dependent on the size, charge, and concentration of the nanoparticle. Here we examine the binding kinetics of human fibrinogen to negatively charged poly(acrylic acid)-coated gold nanoparticles ranging in size from 7 to 22 nm. These particles have previously been shown to elicit an inflammatory response in human cells. The larger nanoparticles bound fibrinogen with increasing affinity and a slower dissociation rate. Each fibrinogen molecule could accommodate two 7 nm nanoparticles but only one when the diameter increased to 10 nm. Nanoparticles larger than 12 nm bound multiple fibrinogen molecules in a positively cooperative manner. However, in the presence of excess nanoparticle, fibrinogen induced aggregation of the larger particles that could bind more than one protein molecule. This is consistent with interparticle bridging by the fibrinogen. Taken together, these results demonstrate that subtle changes in nanoparticle size can influence protein binding both with the surface of the nanoparticle and within the protein corona.

Regimes of Biomolecular Ultrasmall Nanoparticle Interactions

“…As the particle size becomes very small, the interactions with biomolecules are generally expected to diminish, and those that remain may lead to quite different organizations in which multiple particles interact with a single protein, rather than the reverse 9. The fact that the overall biodistribution could result from different size‐dependent effects (physical filtration and biomolecular associations), combined with the absence of any generally accessible and systematic way of studying the nature (or even presence) of these biomolecular associations, makes it difficult to progress systematic understanding of these effects.…”

Regimes of Biomolecular Ultrasmall Nanoparticle Interactions

“…As the particle size becomes very small, the interactions with biomolecules are generally expected to diminish, and those that remain may lead to quite different organizations in which multiple particles interact with as ingle protein, rather than the reverse. [9] Thef act that the overall biodistribution could result from different size-dependent effects (physical filtration and biomolecular associations), combined with the absence of any generally accessible and systematic way of studying the nature (or even presence) of these biomolecular associations,m akes it difficult to progress systematic understanding of these effects.S everal interesting studies have clarified aspects of the biomolecular interactions with ultrasmall nanoparticles. [10] Here,inorder to make contact with the in vivo studies we focus on consequences of particle size and surface on the interactions between USNPs and concentrated biological fluids.Weinvestigate the transition regime between examples in which several proteins can bind relatively irreversibly to the particle,a nd those where all of the proteins are in rapid exchange,and none bind strongly.Wefind this transition to be quite sensitively dependent on small changes in size and surface chemistry.W echose gold as an illustrative system and note the convenience it provides in practical biodistribution studies.…”

The bio-nano-interface in predicting nanoparticle fate and behaviour in living organisms: towards grouping and categorising nanomaterials and ensuring nanosafety by design

“…dots which are typically < 5 nm) the nanomaterials may be smaller than the proteins, as discussed in Klein et al [36] and demonstrated by Deng et al in their study of the role of gold nanoparticle size on binding to fibrinogen, whereby small changes in nanomaterial size (from 8 nm to 10-12 nm to 15 nm) resulted in significant differences in how the protein and nanomaterials interacted [37]. The schematic figures in this manuscript (taken from the literature) are not drawn to scale, but are intended only to illustrate the principles and concepts being described.…”