Assembly of histidine-rich protein materials controlled through divalent cations

Acta Biomater. 2019 Jan 1;83:257-264. doi: 10.1016/j.actbio.2018.10.030. Epub 2018 Oct 24.


Nanostructured protein materials show exciting biomedical applications, since both structure and function can be genetically programmed. In particular, self-assembling histidine-rich proteins benefit from functional plasticity that allows the generation of protein-only nanoparticles for cell targeted drug delivery. However, the rational development of constructs with improved functions is limited by a poor control of the oligomerization process. By exploring cross-interactions between histidine-tagged building blocks, we have identified a critical architectonic role of divalent cations. The obtained data instruct about how histidine-rich protein materials can be assembled, disassembled and reassembled within the nanoscale through the stoichiometric manipulation of divalent ions, in a biochemical approach to biomaterials design. STATEMENT OF SIGNIFICANCE: Divalent metal and non-metal cations such as Ni2+, Cu2+ Ca2+ and Zn2+ have been identified as unexpected molecular tools to control the assembling, disassembling and reassembling of histidine-rich protein materials at the nanoscale. Their stoichiometric manipulation allows generating defined protein-protein cross-molecular contacts between building blocks, for a powerful nano-biochemical manipulation of the material's architecture.

Keywords: Controlled oligomerization; Functional materials; Genetic design; Nanoparticles; Protein materials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cations, Divalent / chemistry*
  • Drug Carriers / chemistry*
  • Metals / chemistry*
  • Nanoparticles / chemistry*
  • Proteins / chemistry*
  • Recombinant Proteins / chemistry


  • Cations, Divalent
  • Drug Carriers
  • Metals
  • Proteins
  • Recombinant Proteins
  • histidine-rich proteins