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Application of isothermal titration calorimetry in evaluation of protein–nanoparticle interactions

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Abstract

Nanoparticles (NPs) offer a number of advantages over small organic molecules for controlling protein behaviour inside the cell. Protein binding to the surface of NPs depends on their surface characteristics, composition and method of preparation (Mandal et al. in J Hazard Mater 248–249:238–245, 2013). It is important to understand the binding affinities, stoichiometries and thermodynamical parameters of NP–protein interactions in order to see which interaction will have toxic and hazardous consequences and thus to prevent it. On the other side, because proteins are on the brink of stability, they may experience interactions with some types of NPs that are strong enough to cause denaturation or significantly change their conformations with concomitant loss of their biological function. Structural changes in the protein may cause exposure of new antigenic sites, “cryptic” peptide epitopes, potentially triggering an immune response which can promote autoimmune disease (Treuel et al. in ACS Nano 8(1):503–513, 2014). Mechanistic details of protein structural changes at NP surface have still remained elusive. Understanding the formation and persistence of the protein corona is critical issue; however, there are no many analytical methods which could provide detailed information about the NP–protein interaction characteristics and about protein structural changes caused by interactions with nanoparticles. The article reviews recent studies in NP–protein interactions research and application of isothermal titration calorimetry (ITC) in this research. The study of protein structural changes upon adsorption on nanoparticle surface and application of ITC in these studies is emphasized. The data illustrate that ITC is a versatile tool for evaluation of interactions between NPs and proteins. When coupled with other analytical methods, it is important analytical tool for monitoring conformational changes in proteins.

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References

  1. Mandal S, Hossain M, Devi PS, Kumar GS, Chaudhuri K. Interaction of carbon nanoparticles to serum albumin:elucidation of the extent of perturbation of serum albumin conformations and thermodynamical parameters. J Hazard Mater. 2013;248–249:238–45.

    Article  Google Scholar 

  2. Treuel L, Brandholt S, Maffre P, Wiegele S, Shang L, Nienhaus GU. Impact of protein modification on the protein corona on nanoparticles and nanoparticle-cell interactions. ACS Nano. 2014;8(1):503–13.

    Article  CAS  Google Scholar 

  3. Aggarwal P, Hall JB, McLeland CB, Dobrovolskai MA, McNeil SE. Nanoparticle interaction with plasma proteins as it relates to particle distribution, biocompatibility and therapeutic efficacy. Adv Drug Deliv Rev. 2009;61:428–37.

    Article  CAS  Google Scholar 

  4. Cukalevski R, Lundqvist M, Oslakovic C, Dahlbäck B, Linse S, Cedervall T. Structural changes in apolipoproteins bound to nanoparticles. Langmuir. 2011;27:14360–9.

    Article  CAS  Google Scholar 

  5. Holmes P, Airborne Particles: Exposure in the Home and Health Effects; Leicester, MRC Instit. Environ. Health 2000.

  6. De Paoli Lacerda SH. Park JJ, Meuse C, Pristinski D, Becker ML, Karim A, Douglas JF. Interaction of gold nanoparticles with common human blood proteins. ACS Nano. 2010;4(1):365–79.

    Article  Google Scholar 

  7. Shemetov AA, Nabiev I, Sukhanova A. Molecular interaction of proteins and peptides with nanoparticles. ACS Nano. 2012;6(6):4585–602.

    Article  CAS  Google Scholar 

  8. Ooi J, Gaisford S, Boyd BJ, Young PM, Traini D. Isothermal calorimetry: a predictive tool to model drug-propellant interactions in pressurized metered dose systems. Int. J. Pharm. 2014; 461: 301-309.

  9. Draczkowski P, Matosiuk D, Jozwiak K. Isothermal titration calorimetry in membrane protein research. J Pharm Biomed Anal. 2014;87:313–5.

    Article  CAS  Google Scholar 

  10. Bouchemal K. New challenges for pharmaceutical formulations and drug delivery systems characterization using isothermal titration calorimetry. Drug Discovery Today. 2008;13(21/22):960–72.

    Article  CAS  Google Scholar 

  11. Houtman JCD, Brown PH, Bowden B, Yamaguchi H, Appella E, Samelson LE, Schuck P. Studying multisite binary and ternary protein interactions by global analysis of isothermal titration calorimetry data in SEDPHAT: application to adaptor protein complexes in cell signalling. Protein Sci. 2007;16:30–42.

    Article  CAS  Google Scholar 

  12. Chakraborty S, Joshi P, Shanker V, Ansari ZA, Singh SP, Chakrabarti P. Contrasting effect of gold nanoparticles and nanorods with different surface modifications on the structure and activity of bovine serum albumin. Langmuir. 2011;27:7722–31.

    Article  CAS  Google Scholar 

  13. Gitlin I, Carbeck JD, Whitesides GM. Why Are Proteins Charged? Networks of Charge-Charge Interactions in Proteins Measured by Charge Ladders and Capillary Electrophoresis. Angew Chem Int Ed. 2006;45:3022–60.

    Article  CAS  Google Scholar 

  14. Alberts B, Bray D, Johnson A, et al. Essential Cell Biology: An Introduction to the Molecular Biology of the Cell. 3rd ed. New York: Garland; 2010.

    Google Scholar 

  15. Saptarshi SR, Duschl A, Lopata AL. Interactions of nanoparticles with proteins: relation to bio-reactivity of the nanoparticle. J. Nanobiotechnology. 2013;11:1–26.

    Article  Google Scholar 

  16. Monopoli MP, Walczyk D, Campbell A, Elia G, Lynch I. Baldelli Bombelli F, Dawson KA. Physical-chemical aspects of protein corona: relevance to in vitro and in vivo biological impacts of nanoparticles. J Am Chem Soc. 2011;133:2525–34.

    Article  CAS  Google Scholar 

  17. Hellstand E, Lynch I, Andersson A, Drakenberg T, Dahlbäck B, Dawson KA, Linse S, Cedervall T. Complete high-density lipoproteins in nanoparticle corona. FEBS J. 2009;276:3372–81.

    Article  Google Scholar 

  18. Ge C, Du J, Zhao L, Wang L, Liu Y, Li D, Yang Y, Zhou R, Zhao Y, Chai Z, Chen C. Binding of blood proteins to carbon nanotubes reduces cytotoxicity. Proc Natl Acad Sci. 2011;108:16968–73.

    Article  CAS  Google Scholar 

  19. dos Santos T, Varela J, Lynch I, Salvati A, Dawson KA. Quantitative Assessment of the Comparative Nanoparticle-Uptake Efficiency of a Range of Cell Lines. Small. 2011;7:3341–9.

    Article  Google Scholar 

  20. Albanese A, Chan WCW. Effect of Gold Nanoparticle Aggregation on Cell Uptake and Toxicity. ACS Nano. 2011;5:5478–89.

    Article  CAS  Google Scholar 

  21. Chanana M. Rivera_Gil P, Correa-Duarte MA, Liz-Marzán LM, Parak WJ. Physicochemical properties of protein-coated gold nanoparticles in biological fluids and cells before and after proteolytic digestion. Angew Chem Int Ed. 2013;52:1–6.

    Article  Google Scholar 

  22. Kreuter J. Mechanism of polymeric nanoparticle-based drug transport across the blood–brain barrier (BBB). J Microencapsul. 2013;30:49–54.

    Article  CAS  Google Scholar 

  23. Kreuter J, Shamenkov D, Petrov V, Ramge P, Cychutek K, Koch-Brandt C, Alyautdin R. Apolipoprotein-mediated transport of nanoparticle-bound drugs across the blood–brain barrier. J Drug Target. 2002;10:317–25.

    Article  CAS  Google Scholar 

  24. Pelaz B, del Pino P, Maffre P, Hartmann R, Gallego M, Rivera-Fernandez S, de la Fuente JM, Nienhaus GU, Parak WJ. Surface Functionalization of Nanoparticles with Polyethylene Glycol (PEG): effects on Protein Adsorption and Cellular Uptake. ACS Nano. 2015;9(7):6996–7008.

    Article  CAS  Google Scholar 

  25. Calatayud MP, Sanz B, Raffa V, Riggio C, Ibarra MR, Goya GF. The effect of surface charge of functionalized Fe3O4 nanoparticles on protein adsorption and cell uptake. Biomaterials. 2014;35(24):6389–99.

    Article  CAS  Google Scholar 

  26. Norde W. My Voyage of Discovery to Proteins in Flatland and Beyond. Colloids Surf. B Biointerfaces. 2008;61:1–9.

    Article  CAS  Google Scholar 

  27. Verma A, Stellacci F. Effect of Surface Properties on Nanoparticle-Cell Interactions. Small. 2010;6:12–21.

    Article  CAS  Google Scholar 

  28. Worrall JWE, Verma A, Yan HH, Rotello VM. “Cleaning” of nanoparticle inhibitors via proteolysis of adsorbed proteins. Chem Commun 2006; 2338–2340.

  29. Colvin VL, Kulinowski KM. Nanoparticles as catalysts for protein fibrillation. Proc Natl Acad Sci. 2007;104:8679–80.

    Article  CAS  Google Scholar 

  30. Wagner SC, Roskamp M, Pallerla M, Araghi RR, Schlecht S, Koksch B. Nanoparticle-Induced Folding and Fibril Formation of Coiled-Coil-Based Model Peptides. Small 201; 6:1321–1328.

  31. Aubin-Tam ME, Hamad-Schifferli K. Gold nanoparticles-cytochrome c complexes: the effect of nanoparticle ligand charge on protein structure. Langmuir. 2005;21:12080–4.

    Article  CAS  Google Scholar 

  32. Cai X, Ramalingam R, Wong HS, Cheng J, Ajuh P, Cheng SH, Lam YW. Characterization of carbon nanotube protein corona by using quantitative proteomics. Nanomedicine. 2013;9:583–93.

    CAS  Google Scholar 

  33. Rocker C, Potzl M, Zhang F, Parak WJ, Nienhaus GU. A Quantitative Fluorescence Study of Protein Monolayer Formation on Colloidal Nanoparticles. Nat Nanotechnol. 2009;5:577–80.

    Article  Google Scholar 

  34. Chithrani BD, Ghazani AA, Chan WCW. Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett. 2006;6:662–8.

    Article  CAS  Google Scholar 

  35. Xia XR, Monteiro-Riviere NA, Riviere JE. An index for characterization of nanomaterials in biological systems. Nat Nanotechnol. 2010;5:671–5.

    Article  CAS  Google Scholar 

  36. Xia XR, Monteiro-Riviere NA, Mathur S, Song X, Xiao L, Oldenberg SJ, Fadeel B, Riviere JE. Mapping the Surface Adsorption Forces of Nanomaterials in Biological Systems. ACS Nano. 2011;5(11):9074–81.

    Article  CAS  Google Scholar 

  37. Dell’Orco D, Lundqvist M, Oslakovic C, Cedervall T, Linse S, Modeling the time evolution of the nanoparticle-protein corona in a body fluid. PLoS One (2010); 5: 10949.

  38. Ghai R, Falconer RJ, Collins BM. Applications of isothermal titration calorimetry in pure and applied research–survey of the literature from 2010. J Mol Recognit. 2012;25:32–52.

    Article  CAS  Google Scholar 

  39. Velazquez-Campoy A, Leavitt SA, Freire E. Characterization of protein-protein interactions by isothermal titration calorimetry. Methods Mol Biol. 2004;261:35–54.

    CAS  Google Scholar 

  40. Leavitt S, Freire E. Direct measurement of protein binding energetics by isothermal titration calorimetry. Curr Opin Struct Biol. 2001;11:560–6.

    Article  CAS  Google Scholar 

  41. Freyer MW, Lewis EA. Isothermal titration calorimetry: experimental design, data analysis, and probing macromolecule/ligand binding and kinetic interactions. Methods Cell Biol. 2008;84:80–113.

    Google Scholar 

  42. Zhou X, Kinin RM, Sivarman J. Application of isothermal titration calorimetry and column chromatography for identification of biomolecular targets. Nat protoc. (2011); 6 No.2: 158-165.

  43. Welsch N, Lu Y, Dzubiella J, Ballauff M. Adsorption of Proteins to Functional Polymeric Nanoparticles. Polymer. 2013;54:2835–49.

    Article  CAS  Google Scholar 

  44. Cedervall T, Lynch I, Lindman S, Berggärd T, Thulin E, Nilsson H, Dawson KA, Linse S. Understanding the nanoparticle-protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles. PNAS.2007; 104(7):2050-2055.

  45. Rajarathnam K, Rösgen J. Isothermal titration calorimetry of membrane proteins – progress and challenges. Biochim Biophys Acta. 2014;1838:69–77.

    Article  CAS  Google Scholar 

  46. Pilloni M, Nicolas J, Marsaud V, Bouchemal K, Frongia F, Scano A, Ennas G, Dubernet C. PEGylation and preliminary biocompatibility evaluation of magnetite-silica nanocomposites obtained by high energy ball milling. Int J Pharm. 2010;401:103–12.

    Article  CAS  Google Scholar 

  47. Grolier JPE, del Rio JM. Isothermal titration calorimetry: A thermodynamic interpretation of measurements.J. Chem. Thermodynamics.2012; 55:193-202.

  48. Pethica BA. Misuse of thermodynamics in the interpretation of isothermal titration calorimetry data for ligand binding to proteins. Anal Biochem. 2015;472:21–9.

    Article  CAS  Google Scholar 

  49. Tonga GY, Mizuhara T, Saha K, Jiang Z, Hou S, Das R, Rotello VM. Binding studies of Cucurbit[7]uril with gold nanoparticles bearing different surface functionalities. Tetrahedron Lett. 2015;56:3653–7.

    Article  Google Scholar 

  50. Fleischer CC, Payne CK. Nanoparticle − Cell Interactions: molecular Structure of the Protein Corona and Cellular Outcome. Acc Chem Res. 2014;47:2651–9.

    Article  CAS  Google Scholar 

  51. Li L, Mu Q, Zhang B, Yan B. Analytical strategies for detecting nanoparticle–protein interactions. Analyst. 2010;135(7):1519–30.

    Article  CAS  Google Scholar 

  52. Eren NM, Narsimhan G, Campanella OH. Protein adsorption induced bridging flocculation: the dominant entropic pathway for nano-bio complexation. Nanoscale. 2016 14;8(6):3326–36.

    Article  CAS  Google Scholar 

  53. Fotticchia I, Fotticchia T, Mattia CA, Giancola C. Chitosan-based nanoparticles studied by isothermal titration calorimetry. J Therm Anal Calorim. 2016;125(2):585–93.

    Article  CAS  Google Scholar 

  54. Darby SJ, Platts L, Daniel MS, Cowieson AJ, Falconer RJ. An isothermal titration calorimetry study of phytate binding. J Therm Anal Calorim. 2016;. doi:10.1007/s10973-016-5487-6.

    Google Scholar 

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Correspondence to Enisa Omanovic-Miklicanin.

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Omanovic-Miklicanin, E., Manfield, I. & Wilkins, T. Application of isothermal titration calorimetry in evaluation of protein–nanoparticle interactions. J Therm Anal Calorim 127, 605–613 (2017). https://doi.org/10.1007/s10973-016-5764-4

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