Use of Protein Cages as a Template for Confined Synthesis of Inorganic and Organic Nanoparticles

  • Masaki Uchida
  • Shefah Qazi
  • Ethan Edwards
  • Trevor DouglasEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1252)


Protein cages are hollow spherical proteins assembled from a defined number of subunits. Because they are extremely homogeneous in size and structure, their interior cavities can serve as ideal templates to encapsulate and synthesize well-defined nanoparticles. Here, we describe the exemplary synthesis of a hard and a soft material in two representative protein cages, i.e., magnetite nanoparticles in ferritin and a poly(2-aminoethyl)methacrylate inside a viral capsid derived from the bacteriophage P22.

Key words

Protein cages Ferritin Viral capsid Biomineralization Atom transfer radical polymerization (ATRP) 



This work was supported with grants from the US Department of Energy, Office of Basic Energy Sciences, Division of Materials Science and Engineering DE-FG02-07ER46477 (for the inorganic nanoparticle work) and the National Institutes of Health NIAID R01AI104905 (for the polymer work).


  1. 1.
    Douglas T, Young M (1998) Host-guest encapsulation of materials by assembled virus protein cages. Nature 393:152–155CrossRefGoogle Scholar
  2. 2.
    Meldrum FC, Wade VJ, Nimmo DL, Heywood BR, Mann S (1991) Synthesis of inorganic nanophase materials in supramolecular protein cages. Nature 349:684–687CrossRefGoogle Scholar
  3. 3.
    Harrison PM, Arosio P (1996) Ferritins: molecular properties, iron storage function and cellular regulation. Biochim Biophys Acta 1275:161–203PubMedCrossRefGoogle Scholar
  4. 4.
    Douglas T, Young M (2006) Viruses: making friends with old foes. Science 312:873–875PubMedCrossRefGoogle Scholar
  5. 5.
    Manchester M, Steinmetz NF (2009) Viruses and nanotechnology, vol 327, Current topics in microbiology and immunology. Springer, BerlinCrossRefGoogle Scholar
  6. 6.
    Uchida M, Klem MT, Allen M, Flenniken ML, Gillitzer E, Varpness Z, Suci P, Young MJ, Douglas T (2007) Protein cage architecture: containers as templates for materials synthesis. Adv Mater 19:1025–1042CrossRefGoogle Scholar
  7. 7.
    Witus LS, Francis MB (2011) Using synthetically modified proteins to make new materials. Acc Chem Res 44:774–783PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Uchida M, Flenniken ML, Allen M, Willits DA, Crowley BE, Brumfield S, Willis AF, Jackiw L, Jutila M, Young MJ, Douglas T (2006) Targeting of cancer cells with ferrimagnetic ferritin cage nanoparticles. J Am Chem Soc 128:16626–16633PubMedCrossRefGoogle Scholar
  9. 9.
    Uchida M, Terashima M, Cunningham CH, Suzuki Y, Willits DA, Willis AF, Yang PC, Tsao PS, McConnell MV, Young MJ, Douglas T (2008) A human ferritin iron oxide nano-composite magnetic resonance contrast agent. Magn Reson Med 60:1073–1081PubMedCrossRefGoogle Scholar
  10. 10.
    Lucon J, Qazi S, Uchida M, Bedwell GJ, LaFrance B, Prevelige PE Jr, Douglas T (2012) Use of the interior cavity of the P22 capsid for site-specific initiation of atom-transfer radical polymerization with high-density cargo loading. Nat Chem 4:781–788PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Chen D-H, Baker ML, Hryc CF, DiMaio F, Jakana J, Wu W, Dougherty M, Haase-Pettingell C, Schmid MF, Jiang W, Baker D, King JA, Chiu W (2011) Structural basis for scaffolding-mediated assembly and maturation of a dsDNA virus. Proc Natl Acad Sci U S A 108:1355–1360PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Lucon J, Edwards E, Qazi S, Uchida M, Douglas T (2013) Atom transfer radical polymerization on the interior of the P22 capsid and incorporation of photocatalytic monomer crosslinks. Eur Polym J 49:2976–2985CrossRefGoogle Scholar
  13. 13.
    Kang S, Uchida M, O’Neil A, Li R, Prevelige PE, Douglas T (2010) Implementation of P22 viral capsids as nanoplatforms. Biomacromolecules 11:2804–2809PubMedCrossRefGoogle Scholar
  14. 14.
    Mantovani G, Lecolley F, Tao L, Haddleton DM, Clerx J, Cornelissen JJ, Velonia K (2005) Design and synthesis of N-maleimido-functionalized hydrophilic polymers via copper-mediated living radical polymerization: a suitable alternative to PEGylation chemistry. J Am Chem Soc 127:2966–2973PubMedCrossRefGoogle Scholar
  15. 15.
    Heredia KL, Bontempo D, Ly T, Byers JT, Halstenberg S, Maynard HD (2005) In situ preparation of protein-“smart” polymer conjugates with retention of bioactivity. J Am Chem Soc 127:16955–16960PubMedCrossRefGoogle Scholar
  16. 16.
    Prevelige PE, Thomas D, King J (1988) Scaffolding protein regulates the polymerization of P22 coat subunits into icosahedral shells in vitro. J Mol Biol 202:743–757PubMedCrossRefGoogle Scholar
  17. 17.
    Teschke CM, McGough A, Thuman-Commike PA (2003) Penton release from P22 heat-expanded capsids suggests importance of stabilizing penton-hexon interactions during capsid maturation. Biophys J 84:2585–2592PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Masaki Uchida
    • 2
  • Shefah Qazi
    • 1
  • Ethan Edwards
    • 1
  • Trevor Douglas
    • 2
    Email author
  1. 1.Department of Chemistry and Biochemistry, Center for Bio-Inspired NanomaterialsMontana State UniversityBozemanUSA
  2. 2.Department of ChemistryIndiana UniversityBloomingtonUSA

Personalised recommendations