Interactions between Nanoparticles and Biomolecules at the Nano-Bio interface

The advancement of nanomedicine and increasing applications of nanoparticles (NPs) in consumer products have led to administered biological exposure and unintentional environmental accumulation of NPs, causing concerns over the safety and sustainability of nanotechnology. Other sources of NP pollutions include combustion processes from human activities, such as petroleum-fueled vehicles. Therefore, there is a crucial need to understand the molecular mechanism of nanotoxicity to ensure safe nanotechnology and enable the vast applications of nanomedicine.

Upon entering biological systems, NPs form molecular complexes with their encountered proteins, termed as the NP-protein corona. Protein corona shields the surface of an exogenous NP and determines its biological identifies. On the other hand, interactions with NP can alter the structure, dynamics, and function of the NP-bound proteins, which may further impact recognition by membrane receptors and the immune system. We hypothesize that the conformational changes of NP-bound proteins are an important determinant of nanotoxicity in additional to other accepted factors, such as ion dissolution and ability for lipid membrane translocation. We apply multiscale computer simulations to understand the structure and dynamics of NP-protein corona, and to evaluate the corresponding conformational changes of the NP-bound proteins. Correlation between computational studies of NP-protein corona and experimental evaluations of NP cytotoxicity will help the development of a predictive metric of nanotoxicity for advancing nanomedicine and environmental remediation of the hazardous by-products of the petroleum industry.

23. I. Javed, Y. Sun, J. Adamcik, B. Wang, A. Kakinen, E. Pilkington, F. Ding, R. Mezzenga, T. Davis, Thomas; P. Ke, “Co-fibrillization of pathogenic and functional amyloid proteins with gold nanoparticles against amyloidogenesis”, Biomacromolecules, in press (2017) DOI: 10.1021/acs.biomac.7b01359

22. E. Pilkington, M. Lai, X. Ge, W. Stanley, B. Wang, M. Wang, A. Kakinen, M. Sani, M. Whittaker, E. Gurzov, F. Ding, J. Quinn, T. Davis, P. Ke, “Star Polymers Reduce IAPP Toxicity via Accelerated Amyloid Aggregation”, Biomacromolecules, in press (2017)

21. J. Yang, B. Wang, Y. You, W. Chang, K. Tang, Y. Wang, W. Zhang, F. Ding, S. Gunasekaran, “Probing the modulated formation of gold nanoparticle-beta lactoglobulin corona complexes and its applications”, Nanoscale, in press (2017) [link]

20. B. Wang, E.H. Pilkington, Y. Sun, T.P. Davis, P.C. Ke and F. Ding, Modulating protein amyloid aggregation with nanomaterials, Environmental Science Nano, in press (2017)

19. N.K. Geitner, W. Zhao, F. Ding, W. Chen, M. R. Wiesner, “Mechanistic Insights from Discrete Molecular Dynamics Simulations of PesticideNanoparticle Interactions”, Environmental Science & Technology, in press (2017) [link]

18. S. Lin, M. Mortimer, R. Chen, A. Kakinen, J.E. Riviere, T.P. Davis, F. Ding,* and P. C. Ke*, “NanoEHS beyond Toxicity – Focusing on Biocorona”, Env. Sci. Nano, in press (2017) [link]

17. Pilkington E.H., Xing Y., Wang B., Kakinen A., Wang M., Davis T.P., Ding F., Ke P.C., “Effects of Protein Corona on IAPP Amyloid Aggregation, Fibril Remodelling, and Cytotoxicity”, Scientific Reports, in press (2017)

16. B. Wang,T. Blin, A. Käkinen, X. Ge, E.H. Pilkington, J.F. Quinn, M.R. Whittaker, T.P. Davis, P.C. Ke and F. Ding, “Brushed polyethylene glycol and phosphorylcholine for grafting nanoparticles against protein binding”, Polymer Chemistry, in press (2016)

15. T. Blin, A. Kakinen, E.H. Pilkington, A. Ivask, F. Ding, J.F. Quinn. M.R. Whittaker, P.C. Ke and T.P. Davis, “Synthesis and In Vitro Properties of Iron Oxide Nanoparticles Grafted with Brushed Phosphorylcholine and Polyethylene Glycol”, Polymer Chemistry, in press (2016)

14. E.N. Gurzov, B. Wang, E.H. Pilkington, P. Chen,A. Kakinen, W.J. Stanley, S.A. Litwak, E.G. Hanssen,T.P. Davis, F. Ding, and P.Chun Ke, “Inhibition of hIAPP Amyloid Aggregation and Pancreatic β-cell Toxicity by OH-terminated PAMAM Dendrimer”, Small, in press (2016)

13. S. Radic, T.P. Davis, P.C. Ke and F. Ding, “Contrasting effects of nanoparticle-protein attraction on amyloid aggregation”, RSC Advances, in press (2015)

12. P. Nedumpully-Govindan, E.N. Gurzov, P. Chen, E.H. Pilkington, W.J. Stanley, S.A. Litwak, T.P. Davis, P.C. Ke, and F. Ding, “Graphene Oxide Inhibits hIAPP Amyloid Fibrillation and Toxicity in Insulin-Producing NIT-1 Cells”, PCCP, in press (2015)

11. Wang B, Geitner NK, Davis TP, Ke PC, Ladner DL and Ding F, “Deviation from the Unimolecular Micelle Paradigm of PAMAM Dendrimers Induced by Strong Inter-Ligand Interactions”, Journal of Physical Chemistry C, in press (2015)

10. Ge XW, Ke PC, Davis TP and Ding F, “A Thermodynamics Model for the Emergence of a Stripe-like Binary SAM on a Nanoparticle Surface”, Small, in press (2015)

9. DeFever R., Geitner N., Bhattacharya P., Ding F., Ke P.C., Sarupria S., “PAMAM dendrimers and graphene: Materials for removing aromatic contaminants from water”, Environmental Science & Technology, in press (2015)

8. Geitner N., Wang B., Andorfer R.; Ladner D.; Ke P.K.; Ding F., “The structure-function relationship of PAMAM dendrimers as robust oil dispersants”, Environmental Science & Technology, 48(21):12868-75, (2014)

7. Wang B., Seabrook S.A., Nedumpully-Govindan P., Chen P., Yin H., Waddington L., Epa V.C., Winkler D.A., Kirby J.K., Ding F., Ke P.C., “Thermostability and Reversibility of Silver Nanoparticle-Protein Binding”, Physical Chemistry Chemical Physics, in press (2014)

6. S. Radic, P. Nedumpully-Govindan,R. Chen, E. Salonen, J.M. Brown, P.C. Ke, and F. Ding, “Effect of Fullerenol Surface Chemistry on Nanoparticle Binding-induced Protein Misfolding”, Nanoscale, in press (2014)

5. Y. Wen, N.K. Geitner, R. Chen, F. Ding, P. Chen, R.E. Andorfer, P.N. Govindan, and P.C. Ke, Binding of Cytoskeletal Proteins with Silver Nanoparticles, RSC Adcances, in press, (2013).

4. EE. Salonen, F. Ding, and P.C. Ke, “Fate, behavior and biophysical modeling of nanoparticles in living systems” in “Engineered Nanoparticles and the Environment: Biophysicochemical Processes and Toxicity”, Edited by B. Xing, C.D. Vecitis, & N. Senesi, Wiley-IUPAC (2016) [download]

3. A. Kakinen, F. Ding, P. Chen, A. Kahru*, and P.C. Ke, “Interaction of Silver Nanoparticles and Firefly Luciferase and Its Impact on Enzyme Luminescence”, Nanotechnology, in press. (2013)

2. S. Radic, N. Geitner, R. Podila, A. Kakinen, P. Chen, P.C. Ke*, and F. Ding*, “Competitive Binding of Natural Amphiphiles with Graphene Derivatives”, Scientific Reports, in press. (2013)

1. F. Ding*, S. Radic, R. Chen, P. Chen, J.M. Brown and P.C. Ke*, “Direct observation of silver nanoparticle-ubiquitin corona formation”, Nanoscale, in press (2012)