Gradated assembly of multiple proteins into supramolecular nanomaterials

Nat Mater. 2014 Aug;13(8):829-36. doi: 10.1038/nmat3998. Epub 2014 Jun 15.

Abstract

Biomaterials exhibiting precise ratios of different bioactive protein components are critical for applications ranging from vaccines to regenerative medicine, but their design is often hindered by limited choices and cross-reactivity of protein conjugation chemistries. Here, we describe a strategy for inducing multiple different expressed proteins of choice to assemble into nanofibres and gels with exceptional compositional control. The strategy employs 'βTail' tags, which allow for good protein expression in bacteriological cultures, yet can be induced to co-assemble into nanomaterials when mixed with additional β-sheet fibrillizing peptides. Multiple different βTail fusion proteins could be inserted into peptide nanofibres alone or in combination at predictable, smoothly gradated concentrations, providing a simple yet versatile route to install precise combinations of proteins into nanomaterials. The technology is illustrated by achieving precisely targeted hues using mixtures of fluorescent proteins, by creating nanofibres bearing enzymatic activity, and by adjusting antigenic dominance in vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biocompatible Materials / chemistry*
  • Carboxylic Ester Hydrolases / chemistry
  • Female
  • Fungal Proteins / chemistry
  • Green Fluorescent Proteins / chemistry
  • Immunohistochemistry
  • Kinetics
  • Macromolecular Substances / chemistry*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Electron, Transmission
  • Nanofibers / chemistry
  • Nanostructures / chemistry*
  • Nanotechnology / methods
  • Peptides / chemistry
  • Protein Structure, Secondary
  • Recombinant Fusion Proteins / chemistry
  • Vaccines / chemistry

Substances

  • Biocompatible Materials
  • Fungal Proteins
  • Macromolecular Substances
  • Peptides
  • Recombinant Fusion Proteins
  • Vaccines
  • Green Fluorescent Proteins
  • Carboxylic Ester Hydrolases
  • cutinase