Protein Nanotechnology: What Is It?

  • Juliet A. Gerrard
Part of the Methods in Molecular Biology book series (MIMB, volume 996)


Protein nanotechnology is an emerging field that is still defining itself. It embraces the intersection of protein science, which exists naturally at the nanoscale, and the burgeoning field of nanotechnology. In this opening chapter, a select review is given of some of the exciting nanostructures that have already been created using proteins, and the sorts of applications that protein engineers are reaching towards in the nanotechnology space. This provides an introduction to the rest of the volume, which provides inspirational case studies, along with tips and tools to manipulate proteins into new forms and architectures, beyond Nature’s original intentions.

Key words

Protein nanotechnology Self-assembly Supramolecular Tecton 


  1. 1.
    Seeman NC (2010) Nanomaterials based on DNA. Annu Rev Biochem 79:65–87PubMedCrossRefGoogle Scholar
  2. 2.
    Tsai CJ, Zhang J, Aleman C, Nussinov R (2006) Structure by design: from single proteins and their building blocks to nanostructures. Trends Biotechnol 24:449–454PubMedCrossRefGoogle Scholar
  3. 3.
    Jaeger L, Chworos A (2006) The architectonics of programmable RNA and DNA nanostructures. Curr Opin Struct Biol 16:531–543PubMedCrossRefGoogle Scholar
  4. 4.
    Rothemund PWK (2006) Folding DNA to create nanoscale shapes and patterns. Nature 440:297–302PubMedCrossRefGoogle Scholar
  5. 5.
    Gazit E (2007) Self-assembled peptide nanostructures: the design of molecular building blocks and their technological utilization. Chem Soc Rev 36:1263–1269PubMedCrossRefGoogle Scholar
  6. 6.
    Matson JB, Zha RH, Stupp SI (2011) Peptide self-assembly for crafting functional biological materials. Curr Opin Solid State Mater Sci 15:225–235PubMedCrossRefGoogle Scholar
  7. 7.
    Woolfson DN, Ryadnov MG (2006) Peptide-based fibrous biomaterials: something old, new and borrowed. Curr Opin Chem Biol 10:559–567PubMedCrossRefGoogle Scholar
  8. 8.
    Howorka S (2011) Rationally engineering natural protein assemblies in nanobiotechnology. Curr Opin Biotechnol 22:485–491PubMedCrossRefGoogle Scholar
  9. 9.
    Heddle JG (2008) Protein cages, rings and tubes: useful components of future nanodevices? Nanotechnol Sci Appl 1:67–78Google Scholar
  10. 10.
    Zhang SG (2002) Emerging biological materials through molecular self-assembly. Biotechnol Adv 20:321–339PubMedCrossRefGoogle Scholar
  11. 11.
    Waterhouse SH, Gerrard JA (2004) Amyloid fibrils in bionanotechnology. Aust J Chem 57:519–523CrossRefGoogle Scholar
  12. 12.
    Ferrari M (2005) Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer 5:161–171PubMedCrossRefGoogle Scholar
  13. 13.
    Ellis-Behnke RG, Liang YX, You SW, Tay DK, Zhang SG, So KF, Schneider GE (2006) Nano neuro knitting: peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision. Proc Natl Acad Sci U S A 103:5054–5059PubMedCrossRefGoogle Scholar
  14. 14.
    Brodin JD, Ambroggio XI, Tang C, Parent KN, Baker TS, Tezcan FA (2012) Metal-directed, chemically tunable assembly of one-, two- and three-dimensional crystalline protein arrays. Nat Chem 4:375–382PubMedCrossRefGoogle Scholar
  15. 15.
    Grunberg R, Serrano L (2010) Strategies for protein synthetic biology. Nucl Acids Res 38:2663–2675PubMedCrossRefGoogle Scholar
  16. 16.
    Whitesides GM, Grzybowski B (2002) Self-assembly at all scales. Science 295:2418–2421PubMedCrossRefGoogle Scholar
  17. 17.
    Nakamoto RK, Baylis Scanlon JA, Al-Shawi MK (2008) The rotary mechanism of the ATP synthase. Arch Biochem Biophys 476:43–50PubMedCrossRefGoogle Scholar
  18. 18.
    Channon K, Bromley EHC, Woolfson DN (2008) Synthetic biology through biomolecular design and engineering. Curr Opin Struct Biol 18:491–498PubMedCrossRefGoogle Scholar
  19. 19.
    O’Leary LER, Fallas JA, Bakota EL, Kang MK, Hartergerink JD (2011) Multi-hierarchical self-assembly of a collagen mimetic peptide from triple helix to nanofibre and hydrogel. Nat Chem 3:821–828PubMedCrossRefGoogle Scholar
  20. 20.
    Almine JF, Bax DV, Mithieux SM, Nivison-Smith L, Rnjak J, Waterhouse A, Wise SG, Weiss AS (2010) Elastin-based materials. Chem Soc Rev 39:3371–3379PubMedCrossRefGoogle Scholar
  21. 21.
    Omenetto FG, Kaplan DL (2010) New opportunities for an ancient material. Science 329:528–531PubMedCrossRefGoogle Scholar
  22. 22.
    Mason JM, Arndt KM (2004) Coiled coil domains: stability, specificity, and biological implications. Chembiochem 5:170–176PubMedCrossRefGoogle Scholar
  23. 23.
    Apostolovic B, Danial M, Harm-Anton Klok H-A (2010) Coiled coils: attractive protein folding motifs for the fabrication of self-assembled, responsive and bioactive materials. Chem Soc Rev 39:3541–3575PubMedCrossRefGoogle Scholar
  24. 24.
    Gras SL, Tickler AK, Squires AM, Devlin GL, Horton MA, Dobson CM, MacPhee CE (2008) Functionalised amyloid fibrils for roles in cell adhesion. Biomaterials 29:1553–1562PubMedCrossRefGoogle Scholar
  25. 25.
    Cherny I, Gazit E (2008) Amyloids: not only pathological reagents but also ordered nanomaterials. Angew Chem 47:4062–4069CrossRefGoogle Scholar
  26. 26.
    Allen M, Willits D, Young M, Douglas T (2003) Constrained synthesis of cobalt oxide nanomaterials in the 12-subunit protein cage from Listeria innocua. Inorg Chem 42:6300–6305PubMedCrossRefGoogle Scholar
  27. 27.
    Uchida M, Flenniken ML, Allen M, Willits DA, Crowley BE, Brumfield S, Willis AF, Jackiw L, Jutila M, Young MJ (2006) Targeting of cancer cells with ferrimagnetic ferritin cage nanoparticles. J Am Chem Soc 128:16626–16633PubMedCrossRefGoogle Scholar
  28. 28.
    Cardinale D, Carette N, Michon T (2012) Virus scaffolds as enzyme nano-carriers. Trends Biotechnol 30:369–376PubMedCrossRefGoogle Scholar
  29. 29.
    Astier Y, Bayley H, Howorka S (2005) Protein components for nanodevices. Curr Opin Chem Biol 9:576–584PubMedCrossRefGoogle Scholar
  30. 30.
    Clarke J, Regan L (2010) Protein engineering and design: from first principles to new technologies. Curr Opin Struct Biol 20:480–481PubMedCrossRefGoogle Scholar
  31. 31.
    Das R, Baker D (2008) Macromolecular modeling with Rosetta. Annu Rev Biochem 77:363–382PubMedCrossRefGoogle Scholar
  32. 32.
    Kaufmann KW, Lemmon GH, DeLuca SL, Sheehan JH, Meiler J (2010) Practically useful: what the ROSETTA protein modeling suite can do for you. Biochemistry 49:2987–2998PubMedCrossRefGoogle Scholar
  33. 33.
    Heddle JG, Yokoyama T, Yamashita I, Park SY, Tame JRH (2006) Rounding up: engineering 12-membered rings from the cyclic 11-Mer TRAP. Structure 14:925–933PubMedCrossRefGoogle Scholar
  34. 34.
    Heddle JG, Fujiwara I, Yamadaki H, Yoshii S, Nishio K, Addy C, Yamashita I, Tame JRH (2007) Using the ring shaped protein TRAP to capture and confine gold nanodots on a surface. Small 3:1950–1956PubMedCrossRefGoogle Scholar
  35. 35.
    Miranda FF, Iwasaki K, Akashi S, Sumitomo K, Kobayashi M, Yamashita I, Tame JRH, Heddle JG (2009) A self‐assembled protein nanotube with high aspect ratio. Small 5:2077–2084PubMedCrossRefGoogle Scholar
  36. 36.
    Wang WX, Dgany O, Wolf SG, Levy I, Algom R, Pouny Y, Wolf A, Marton I, Altman A, Shoseyov O (2006) Aspen SP1, an exceptional thermal, protease and detergent resistant self assembled nano particle. Biotechnol Bioeng 95:161–168PubMedCrossRefGoogle Scholar
  37. 37.
    Heyman A, Levy I, Altman A, Shoseyov O (2007) SP1 as a novel scaffold building block for self-assembly nanofabrication of submicron enzymatic structures. Nano Lett 7:1575–1579PubMedCrossRefGoogle Scholar
  38. 38.
    Medalsy I, Dgany O, Sowwan M, Cohen H, Yukashevska A, Wolf SG, Wolf A, Koster A, Almog O, Marton I (2008) SP1 protein-based nanostructures and arrays. Nano Lett 8:473–477PubMedCrossRefGoogle Scholar
  39. 39.
    Frasconi M, Heyman A, Medalsy I, Porath D, Mazzei F, Shoseyov O (2011) Wiring of redox enzymes on three dimensional self-assembled molecular scaffold. Langmuir 27:12606–12613PubMedCrossRefGoogle Scholar
  40. 40.
    Medalsy I, Klein M, Heyman A, Shoseyov O, Remacle F, Levine RD, Porath D (2010) Logic implementations using a single nanoparticle-protein hybrid. Nat Nanotechnol 5:451–457PubMedCrossRefGoogle Scholar
  41. 41.
    Mougous JD, Cuff ME, Raunser S, Shen A, Zhou M, Gifford CA, Goodman AL, Joachimiak G, Ordoñez CL, Lory S (2006) A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus. Science 312:1526PubMedCrossRefGoogle Scholar
  42. 42.
    Ballister ER, Lai AH, Zuckermann RN, Cheng Y, Mougous JD (2008) In vitro self-assembly of tailorable nanotubes from a simple protein building block. Proc Natl Acad Sci U S A 105:3733–3738PubMedCrossRefGoogle Scholar
  43. 43.
    Schreiber A, Zaitseva E, Thomann Y, Thomann R, Dengjel J, Hanselmann R, Schiller SM (2011) Protein yoctowell nanoarchitectures: assembly of donut shaped protein containers and nanofibres. Soft Matter 7:2875–2878CrossRefGoogle Scholar
  44. 44.
    McMillan RA, Paavola CD, Howard J, Chan SL, Zaluzec NJ, Trent JD (2002) Ordered nanoparticle arrays formed on engineered chaperonin protein templates. Nat Mater 1:247–252PubMedCrossRefGoogle Scholar
  45. 45.
    Padilla JE, Colovos C, Yeates TO (2001) Nanohedra: using symmetry to design self assembling protein cages, layers, crystals, and filaments. Proc Natl Acad Sci U S A 98:2217–2221PubMedCrossRefGoogle Scholar
  46. 46.
    Grueninger D, Treiber N, Ziegler MOP, Koetter JWA, Schulze MS, Schulz GE (2008) Designed protein-protein association. Science 319:206–209PubMedCrossRefGoogle Scholar
  47. 47.
    Lai Y-T, Cascio D, Yeates TO (2012) Structure of a 16 nm cage designed by using protein oligomers. Science 336:1129PubMedCrossRefGoogle Scholar
  48. 48.
    Tsai C-J, Zheng J, Zanuy D, Haspel N, Wolfson H, Alema C, Nussinov R (2007) Principles of nanostructure design with protein building blocks. Prot Struct Funct Bioinform 68:1–12CrossRefGoogle Scholar
  49. 49.
    Grove TZ, Hands M, Regan L (2010) Creating novel proteins by combining design and selection. Prot Eng Design Select 23:449–455CrossRefGoogle Scholar
  50. 50.
    Fegan A, White B, Carlson JCT, Wagner CR (2010) Chemically controlled protein assembly: techniques and applications. Chem Rev 110:3315–3336PubMedCrossRefGoogle Scholar
  51. 51.
    Sinclair JC (2012) Self-assembly: proteins on parade. Nat Chem 4:346–347PubMedCrossRefGoogle Scholar
  52. 52.
    Woolfson DN (2010) Building fibrous biomaterials from α-helical and collagen-like coiled-coil peptides. Biopolymers 94:118–127PubMedCrossRefGoogle Scholar
  53. 53.
    Wagner DE, Philips CL, Ali WM, Nybakken GE, Crawford ED, Schwab AD, Smith WF, Fairman R (2005) Towards the development of peptide nanofilaments and nanoropes as smart materials. Proc Natl Acad Sci U S A 102:12656–12661PubMedCrossRefGoogle Scholar
  54. 54.
    Kohli P, Martin CR (2005) Smart nanotubes for biotechnology. Curr Pharm Biotechnol 6:35–41, Curr Opin Biotech 17:562–568PubMedGoogle Scholar
  55. 55.
    Ulijn RJ, Woolfson DN (2010) Peptide and protein based materials in 2010: from design and structure to function and application. Chem Soc Rev 39:3349–3350PubMedCrossRefGoogle Scholar
  56. 56.
    Maskarinec SA, Tirrell DA (2005) Protein engineering approaches to biomaterials design. Curr Opin Biotechnol 16:422–426PubMedCrossRefGoogle Scholar
  57. 57.
    Grove TZ, Forster J, Pimienta G, Dufresne E, Regan L (2012) A modular approach to the design of protein-based smart gels. Biopolymers 97:508–517PubMedCrossRefGoogle Scholar
  58. 58.
    Buehler MJ, Yung YC (2009) Deformation and failure of protein materials in physiologically extreme conditions and disease. Nat Mater 8:175–188PubMedCrossRefGoogle Scholar
  59. 59.
    Shaikh Mohammed J, Murphy WL (2009) Bioinspired design of dynamic materials. Adv Mater 21:2361–2374CrossRefGoogle Scholar
  60. 60.
    Asuri P, Bale SS, Karajanagi SS, Kane RS (2006) The protein–nanomaterial interface. Curr Opin Biotechnol 9:562–568CrossRefGoogle Scholar
  61. 61.
    Woolfson DN, Mahmoud ZN (2010) More than just bare scaffolds: towards multi-component and decorated fibrous biomaterials. Chem Soc Rev 39:3464–3479PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, New York 2013

Authors and Affiliations

  • Juliet A. Gerrard
    • 1
    • 2
  1. 1.Biomolecular Interaction Centre and School of Biological SciencesUniversity of Canterbury, MacDiarmid Institute for Advanced Materials and Nanotechnology, Riddet InstituteChristchurchNew Zealand
  2. 2.Callaghan Innovation Research LimitedLower HuttNew Zealand

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