Engineered nanomaterials have unique electrical, mechanical and physicochemical properties with potential to benefit our society. However, the health and safety of nanomaterials has recently become a great concern to the public, policymakers and regulatory agencies. Such concern is justified due to the vast potential use of nanomaterials in food, cosmetics, medicine, construction, manufacturing, and the environment. It has recently been established that nanomaterials, upon entry into the bloodstream or lung, exhibit a natural tendency of physical adsorption with proteins, peptides, lipids and amino acids to render a protein """"""""corona"""""""" that may dictate the bioavailability and distribution of nanomaterials within the host system, at the cellular, tissue and organism level. Consequently, the objective of this application is to delineate the dynamic roles of nanoparticle-protein corona on biological responses to engineered nanomaterials for safe nanotechnologies and nanomedicines. Determining the health and safety implications of the nanoparticle-protein corona requires addressing the fundamental aspects of 1) dynamics and conformational changes resulting from competitive binding, crowding and degradation of the proteins, and 2) recognition of the protein corona by cellular receptors and immune responses. The central hypothesis of this project is that the physicochemical properties of the nanoparticle-protein corona entity are correlated with biological responses to the corona to impact on their uptake and hypersensitivity reactions. We will test this hypothesis by pursuing three specific aims: 1) Understand nanoparticle-protein interaction and transformation;2) Determine the in silico structure and dynamics of protein corona;3) Determine the in vitro impact of nanoparticle-protein corona on directing cellular uptake, ER stress and the unfolded protein response. The rationale of this application is that understanding the impact of nanoparticle-protein corona on cellular recognition, uptake and response is crucial for predicting toxicity and developing safe nanotechnologies. In addition, this R15 project is expected to contribute to the training of a new generation of scientists at the interface of biophysics and biomedicine and facilitate future NIH funding opportunities for Clemson University and East Carolina University.

Public Health Relevance

The unique properties that make nanomaterials a focus of science, technology and medicine also present health and safety concerns. This current proposal is aligned with the mission of the NIEHS in that it addresses the implications of the nanoparticle-protein corona by i) elucidating the physicochemical properties and dynamics of plasma and cytoskeletal proteins interacting with nanoparticles of different surface charge, coating, and morphology;and ii) determining the impact of these coronas by membrane receptors with the connections to unfolded protein responses and ER stress. This research is compatible with the NIH-AREA funding mechanism in that it will provide a unique cross-disciplinary training environment for undergraduate and graduate students in experimental and computational biophysics, cell biology and toxicology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15ES022766-01A1
Application #
8625112
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Nadadur, Srikanth
Project Start
2014-09-04
Project End
2017-08-31
Budget Start
2014-09-04
Budget End
2017-08-31
Support Year
1
Fiscal Year
2014
Total Cost
$444,826
Indirect Cost
$99,034
Name
Clemson University
Department
Physics
Type
Schools of Engineering
DUNS #
042629816
City
Clemson
State
SC
Country
United States
Zip Code
29634
Nedumpully-Govindan, Praveen; Gurzov, Esteban N; Chen, Pengyu et al. (2016) Graphene oxide inhibits hIAPP amyloid fibrillation and toxicity in insulin-producing NIT-1 cells. Phys Chem Chem Phys 18:94-100
Nedumpully-Govindan, Praveen; Kakinen, Aleksandr; Pilkington, Emily H et al. (2016) Stabilizing Off-pathway Oligomers by Polyphenol Nanoassemblies for IAPP Aggregation Inhibition. Sci Rep 6:19463
Mallineni, Sai Sunil Kumar; Shannahan, Jonathan; Raghavendra, Achyut J et al. (2016) Biomolecular Interactions and Biological Responses of Emerging Two-Dimensional Materials and Aromatic Amino Acid Complexes. ACS Appl Mater Interfaces 8:16604-11
Gurzov, Esteban N; Wang, Bo; Pilkington, Emily H et al. (2016) Inhibition of hIAPP Amyloid Aggregation and Pancreatic β-Cell Toxicity by OH-Terminated PAMAM Dendrimer. Small 12:1615-26
Ratnikova, Tatsiana A; Podila, Ramakrishna; Rao, Apparao M et al. (2015) Tomato Seed Coat Permeability to Selected Carbon Nanomaterials and Enhancement of Germination and Seedling Growth. ScientificWorldJournal 2015:419215
Wang, Bo; Seabrook, Shane A; Nedumpully-Govindan, Praveen et al. (2015) Thermostability and reversibility of silver nanoparticle-protein binding. Phys Chem Chem Phys 17:1728-39
Sengupta, Bishwambhar; Gregory, Wren E; Zhu, Jingyi et al. (2015) Influence of carbon nanomaterial defects on the formation of protein corona. RSC Adv 5:82395-82402
Radic, Slaven; Davis, Thomas P; Ke, Pu Chun et al. (2015) Contrasting effects of nanoparticle-protein attraction on amyloid aggregation. RSC Adv 5:105498
Nedumpully-Govindan, Praveen; Yang, Ye; Andorfer, Rachel et al. (2015) Promotion or Inhibition of Islet Amyloid Polypeptide Aggregation by Zinc Coordination Depends on Its Relative Concentration. Biochemistry 54:7335-44
Ge, Xinwei; Ke, Pu Chun; Davis, Thomas P et al. (2015) A Thermodynamics Model for the Emergence of a Stripe-like Binary SAM on a Nanoparticle Surface. Small 11:4894-9

Showing the most recent 10 out of 11 publications