Role of Albumin in the Formation and Stabilization of Nanoparticle Aggregates in Serum Studied by Continuous Photon Correlation Spectroscopy and Multiscale Computer Simulations

Bhirde, Ashwinkumar; Hassan, Sergio A.; Harr, Erick; Chen, Xiaoyuan

doi:10.1021/jp5034068

Cited by 33 publications

(26 citation statements)

References 45 publications

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“…An estimate of the relative importance of crowding and depletion forces in driving NP aggregation and its dependence on NP size requires a realistic, yet computationally tractable representation of the biological medium. This can be accomplished by multiscale Monte Carlo simulations 49 and will be reported in a follow up study.…”

Section: Resultsmentioning

confidence: 99%

Biointeractions of ultrasmall glutathione-coated gold nanoparticles: effect of small size variations

et al. 2016

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Recent in vivo studies have established ultrasmall (< 3 nm) gold nanoparticles coated with glutathione (AuGSH) as a promising platform for applications in nanomedicine. However, systematic in vitro investigations to gain a more fundamental understanding of the particles’ biointeractions are still lacking. Herein we examined the behavior of ultrasmall AuGSH in vitro, focusing on their ability to resist aggregation and adsorption from serum proteins. Despite having net negative charge, AuGSH particles were colloidally stable in biological media and able to resist binding from serum proteins, in agreement with the favorable bioresponses reported for AuGSH in vivo. However, our results revealed disparate behaviors depending on nanoparticle size: particles between 2 and 3 nm in core diameter were found to readily aggregate in biological media, whereas those strictly under 2 nm were exceptionally stable. Molecular dynamics simulations provided microscopic insight into interparticle interactions leading to aggregation and their sensitivity to the solution composition and particle size. These results have important implications, in that seemingly small variations in size can impact the biointeractions of ultrasmall AuGSH, and potentially of other ultrasmall nanoparticles as well.

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Section: Resultsmentioning

confidence: 99%

Biointeractions of ultrasmall glutathione-coated gold nanoparticles: effect of small size variations

et al. 2016

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“…A step towards the inclusion of such solvent effects was performed by Carrillo-Parramon et al Models developed specifically for protein structures near interfaces have been proposed in several studies. Bhirde et al (2014) modeled the aggregation of gold nanoparticles in an albumin solution using a rigid-body CG model of inter-nanoparticle, inter-and intra-protein and nanoparticle-protein interactions consisting of a 12-6 Lennard-Jones term for all three types of interactions and an electrostatic term for protein-protein interactions based on the screened Coulomb potential implicit solvent model (SCPISM) (Cardone et al 2013;Hassan & Steinbach, 2011). They investigated the role of nanoparticle size and coating of its surface in adsorption of albumin by performing a number of MC simulations with different resolutions of coarse-graining and different values of the Lennard-Jones parameters (σ and ε) and the nanoparticle concentration.…”

Section: Coarse-grained Molecular Mechanics Modeling Of Protein-surfamentioning

confidence: 99%

Modeling and simulation of protein–surface interactions: achievements and challenges

Ozboyaci

Kokh

Corni

et al. 2016

Quart. Rev. Biophys.

196

199

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Abstract. Understanding protein-inorganic surface interactions is central to the rational design of new tools in biomaterial sciences, nanobiotechnology and nanomedicine. Although a significant amount of experimental research on protein adsorption onto solid substrates has been reported, many aspects of the recognition and interaction mechanisms of biomolecules and inorganic surfaces are still unclear. Theoretical modeling and simulations provide complementary approaches for experimental studies, and they have been applied for exploring protein-surface binding mechanisms, the determinants of binding specificity towards different surfaces, as well as the thermodynamics and kinetics of adsorption. Although the general computational approaches employed to study the dynamics of proteins and materials are similar, the models and force-fields (FFs) used for describing the physical properties and interactions of material surfaces and biological molecules differ. In particular, FF and water models designed for use in biomolecular simulations are often not directly transferable to surface simulations and vice versa. The adsorption events span a wide range of time-and length-scales that vary from nanoseconds to days, and from nanometers to micrometers, respectively, rendering the use of multi-scale approaches unavoidable. Further, changes in the atomic structure of material surfaces that can lead to surface reconstruction, and in the structure of proteins that can result in complete denaturation of the adsorbed molecules, can create many intermediate structural and energetic states that complicate sampling. In this review, we address the challenges posed to theoretical and computational methods in achieving accurate descriptions of the physical, chemical and mechanical properties of protein-surface systems. In this context, we discuss the applicability of different modeling and simulation techniques ranging from quantum mechanics through all-atom molecular mechanics to coarse-grained approaches. We examine uses of different sampling methods, as well as free energy calculations. Furthermore, we review computational studies of protein-surface interactions and discuss the successes and limitations of current approaches.

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“…Ultrasmall NPs could interact with proteins in a variety of modes and with a broad range of affinities and association and dissociation rates. Simulations in model systems have shown 27 that weak, nonspecific NP–protein association can lead to the formation of porous aggregates, i.e ., amorphous mixtures of NPs and proteins, the cohesive energy of which could be controlled by a judicious choice of coating chemistry and NP size. It has been suggested 27 that small labile aggregates may offer advantages over dissociated NPs, as they may protect the functionalized surfaces from degradation in the bloodstream or upon internalization.…”

Section: Discussionmentioning

confidence: 99%

“…The NPs and the CC species were modeled as hardcore spheres of radii R i = (3 v i /4π) 1/3 , where v i is the time-averaged molecular volume of species i calculated from MD simulations in pure water; for the NPs, R ≈ 1.44 nm (AuNP-14) and R ≈ 1.96 nm (AuNP-25), implying an effective coating thickness slightly above ~0.7 nm in both cases. To account for the unique shape of HSA, a coarse-grained model was used as described earlier, 27 with effective particles modeled as uncharged hardcore spheres. The simulations were conducted in a spherical hard-wall container of 0.18 µ m in diameter ( cf .…”

Section: Methodsmentioning

confidence: 99%

Computational Study of the Forces Driving Aggregation of Ultrasmall Nanoparticles in Biological Fluids

Hassan

2017

ACS Nano

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Nanoparticle (NP) aggregation can lead to prolonged retention in tissues or embolism, among other adverse effects. Successful use in biomedicine thus requires the capability to make NPs with limited aggregative : potential. Rational design is presently a challenge due to incomplete knowledge of their interactions in biofluids. Recently, ultrasmall gold NPs passivated with endogenous antioxidant glutathione have shown promise for use in vivo. Computer simulations are here conducted to identify the forces underlying aggregation (or lack thereof) of these NPs in a cell culture. Electrostatic interactions are insufficient to induce association, but the van der Waals forces exerted by cations, anions, and net-neutral polar species can promote the formation of stable dimers. The entropic effects of depletion are negligible, but the combined effect of depletion and macromolecular crowding at physiological concentrations can stabilize aggregates containing just a few NPs. Interparticle interactions are controlled by modest changes in both the structure and dynamic of the interfacial liquid. The molecular origin of these effects and their dependence on NP size are described. The liquid is shown to be highly structured, with large and long-lived hydrogen-bonded water clusters developing often in the interparticle space; their potential role as transient, long-range proton wires connecting and enveloping neighboring NPs is discussed. The basis for a parsimonious theory of ultrasmall NPs in complex fluids is established.

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Role of Albumin in the Formation and Stabilization of Nanoparticle Aggregates in Serum Studied by Continuous Photon Correlation Spectroscopy and Multiscale Computer Simulations

Cited by 33 publications

References 45 publications

Biointeractions of ultrasmall glutathione-coated gold nanoparticles: effect of small size variations

Biointeractions of ultrasmall glutathione-coated gold nanoparticles: effect of small size variations

Modeling and simulation of protein–surface interactions: achievements and challenges

Computational Study of the Forces Driving Aggregation of Ultrasmall Nanoparticles in Biological Fluids

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