Paper NS+NC-ThM6
Self-Assembly of Nanostructures and Nanocomposites using De Novo Designed Helix- Loop- Helix Polypeptides

Thursday, October 23, 2008, 9:40 am, Room 311

Self-assembly has emerged as a promising and powerful technique for fabrication of complex hybrid materials and nanocomposites. This contribution will discuss how folding of a set of de novo designed polypeptides can be utilized for the assembly of fibers, fibrous nanostructures and gold nanoparticles. The 42-mer polypeptides fold into four-helix bundles upon dimerization. The peptides are rich in either Glu or Lys which render them a high negative or positive net charge, respectively. Charge repulsion prevents homodimerization at neutral pH while promoting heterodimerization through the formation of stabilizing salt bridges. For the Glu rich polypeptide, homodimerization can be induced at acidic (pH<6) or by addition of certain metal ions, such as Zn²⁺.¹ The polypeptides have a single Cys in the loop region to facilitate directed immobilization onto gold substrates. The Cys can also be utilized to connect two polypeptides via a disulphide bridge. The disulphide-linked polypeptides spontaneously and rapidly assemble into micrometer long fibers with a diameter < 5 nm as a result of a propagating association mediated by folding. In addition, the fibers have been observed to assemble into highly symmetric nano-rings. Furthermore, the polypeptides enable reversible, folding induced assembly of gold nanoparticles with defined interparticle distances.¹ Aggregation of polypeptide functionalized nanoparticles can be induced in a number of ways utilizing the highly specific interactions involved in both homodimerization and hetero-association. Furthermore, particle aggregation can be utilized to induce folding of the immobilized polypeptides. Helix-loop-helix polypeptides can also be utilized as a robust scaffold, or synthetic receptor, for biosensor applications.² The sensor scaffold was, as a proof of concept, site-selectively modified with a benzenesulfonamide moiety that provides a specific recognition site for Human Carbonic Anhydrase II (HCAII). Gold nanoparticles functionalized with the sensor polypeptide enabled simple colorimetric detection of HCAII.

¹D. Aili, K. Enander, J. Rydberg, I. Nesterenko, F. Björefors, L. Baltzer, B. Liedberg, J. Am. Chem. Soc. 2008, 130, 5780-5788.
²K. Enander, G. T. Dolphin, L. Baltzer, J. Am. Chem. Soc. 2004, 126, 4464.