skip to main content

Attention:

The NSF Public Access Repository (PAR) system and access will be unavailable from 11:00 PM ET on Thursday, January 16 until 2:00 AM ET on Friday, January 17 due to maintenance. We apologize for the inconvenience.

Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


This content will become publicly available on January 21, 2025

Title: Protein Binding Leads to Reduced Stability and Solvated Disorder in the Polystyrene Nanoparticle Corona
Abstract

Understanding the conformation of proteins in the nanoparticle corona has important implications in how organisms respond to nanoparticle‐based drugs. These proteins coat the nanoparticle surface, and their properties will influence the nanoparticle's interaction with cell targets and the immune system. While some coronas are thought to be disordered, two key unanswered questions are the degree of disorder and solvent accessibility. Here, a model is developed for protein corona disorder in polystyrene nanoparticles of varying size. For two different proteins, it is found that binding affinity decreases as nanoparticle size increases. The stoichiometry of binding, along with changes in the hydrodynamic size, supports a highly solvated, disordered protein corona anchored at a small number of attachment sites. The scaling of the stoichiometry versus nanoparticle size is consistent with disordered polymer dimensions. Moreover, it is found that proteins are destabilized less in the presence of larger nanoparticles, and hydrophobic exposure decreases at lower curvatures. The observations hold for proteins on flat polystyrene surfaces, which have the lowest hydrophobic exposure. The model provides an explanation for previous observations of increased amyloid fibrillation rates in the presence of larger nanoparticles, and it may rationalize how cell receptors can recognize protein disorder in therapeutic nanoparticles.

  more » « less
PAR ID:
10487085
Author(s) / Creator(s):
 ;  ;  ;  ;  ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Small
Volume:
20
Issue:
26
ISSN:
1613-6810
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ( , Bioconjugate Chemistry)
    The interaction between lipid nanoparticles (LNPs) and serum proteins, giving rise to a unique identification in the form of the protein corona, has been shown to be associated with novel recognition by cell receptors. The presence of the corona enveloping the nanoparticle strongly affects the interplay with immune cells. The immune responses mediated by protein corona can affect nanoparticle toxicity and targeting capabilities. But the intracellular signaling of LNPs after corona formation resulting in the change of nanoparticles’ ability to provoke immune responses remains unclear. Therefore, a more systematic and delineated approach must be considered to present the correlation between corona complexes and the shift in nanoparticle immunogenicity. Here, we studied and reported the inhibiting effect of the absorbed proteins on the LNPs on the NLRP3 inflammasome activation, a key intracellular protein complex that modulates several inflammatory responses. Ionizable lipid as a component of LNP was observed to play an important role in modulating the activation of NLRP3 inflammasome in serum-free conditions. However, in the presence of serum proteins, the corona layer on LNPs caused a significant reduction in the inflammasome activation. Reduction in the lysosomal rupture after treatment with corona-LNPs significantly reduced inflammasome activation. Furthermore, a strong reduction of cellular uptake in macrophages after the corona formation was observed. On inspecting the uptake mechanisms in macrophages using transport inhibitors, lipid formulation was found to play a critical role in determining the endocytic pathways for the LNPs in macrophages. This study highlights the need to critically analyze the protein interactions with nanomaterials and their concomitant adaptability with immune cells to evaluate nano–bio surfaces and successfully design nanomaterials for biological applications. 
    more » « less
  2. ; ; ; ( , Nature Communications)
    Abstract

    The orientation adopted by proteins on nanoparticle surfaces determines the nanoparticle’s bioactivity and its interactions with living systems. Here, we present a residue-based affinity scale for predicting protein orientation on citrate-gold nanoparticles (AuNPs). Competitive binding between protein variants accounts for thermodynamic and kinetic aspects of adsorption in this scale. For hydrophobic residues, the steric considerations dominate, whereas electrostatic interactions are critical for hydrophilic residues. The scale rationalizes the well-defined binding orientation of the small GB3 protein, and it subsequently predicts the orientation and active site accessibility of two enzymes on AuNPs. Additionally, our approach accounts for the AuNP-bound activity of five out of six additional enzymes from the literature. The model developed here enables high-throughput predictions of protein behavior on nanoparticles, and it enhances our understanding of protein orientation in the biomolecular corona, which should greatly enhance the performance and safety of nanomedicines used in vivo.

     
    more » « less
  3. ; ; ; ; ; ( , Environmental Science: Nano)
    null (Ed.)
    Biomolecular coatings (coronas) that form on nanomaterials have been widely investigated in animal and bacterial cell culture and in the extracellular and intracellular fluids of animals. Such coronas influence the distribution of nanoparticles within organisms, their uptake by cells, and their storage in intracellular compartments. Plants can be exposed to nanoparticles via either intentional application of nanomaterials in agriculture or inadvertently due, for example, to biosolids amendment of soils. Development of a mechanistic understanding of nanoparticle transport and fate within plants requires consideration of corona acquisition within plants, particularly within the vascular fluids that transport nanoparticles throughout plants. Here, we examine the interactions between copper oxide (CuO) nanoparticles and pumpkin xylem fluid to understand corona formation in an important part of the plant vasculature system. We used CuO nanoparticles because they have emerged as a promising micronutrient source for the suppression of fungal diseases. The corona was composed primarily of proteins, despite the higher abundance of carbohydrates in xylem fluid. We used X-ray photoelectron spectroscopy to determine the thickness of the protein corona. Polyacrylamide gel electrophoresis revealed that protein binding to the CuO nanoparticle surface was selective; the most abundant proteins in the corona were not the most abundant ones in the xylem fluid. We used in situ attenuated total reflectance Fourier-transform infrared spectroscopy to show that the protein–CuO NP interactions were quasi-irreversible, while carbohydrate–CuO interactions were reversible. Corona formation is expected to influence the distribution and transformation of nanomaterials in plants. 
    more » « less
  4. ; ( , Frontiers in Physiology)
    The spontaneous formation of a protein corona on a nanoparticle surface influences the physiological success or failure of the synthetic nanoparticle as a drug carrier or imaging agent used in vivo . A quantitative understanding of protein-nanoparticle interactions is therefore critical for the development of nanoparticle-based therapeutics. In this perspective, we briefly discuss the challenges and limitations of current approaches used for studying protein-nanoparticle binding in a realistic biological medium. Subsequently, we demonstrate that solution nuclear magnetic resonance (NMR) spectroscopy is a powerful tool to monitor protein competitive binding in a complex serum medium in situ . Importantly, when many serum proteins are competing for a gold nanoparticle (AuNP) surface, solution NMR is able to detect differences in binding thermodynamics, and kinetics of a tagged protein. Combined with other experimental approaches, solution NMR is an invaluable tool to understand protein behavior in the nanoparticle corona. 
    more » « less
  5. ; ; ( , Nucleic Acids Research)
    Abstract

    Intrinsic disorder in proteins is relatively abundant in nature and essential for a broad spectrum of cellular functions. While disorder can be accurately predicted from protein sequences, as it was empirically demonstrated in recent community-organized assessments, it is rather challenging to collect and compile a comprehensive prediction that covers multiple disorder functions. To this end, we introduce the DEPICTER2 (DisorderEd PredictIon CenTER) webserver that offers convenient access to a curated collection of fast and accurate disorder and disorder function predictors. This server includes a state-of-the-art disorder predictor, flDPnn, and five modern methods that cover all currently predictable disorder functions: disordered linkers and protein, peptide, DNA, RNA and lipid binding. DEPICTER2 allows selection of any combination of the six methods, batch predictions of up to 25 proteins per request and provides interactive visualization of the resulting predictions. The webserver is freely available at http://biomine.cs.vcu.edu/servers/DEPICTER2/

     
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email