Design and characterization of peptide-capped nanoparticles with controlled molecular structure: towards artificial proteins

Secondary supervisors: Martin Volk (Liverpool), Michael Sullivan (A* Singapore), Jonathan Hobley (A* Singapore)

In the past two decades, a range of water-soluble multifunctional nanomaterials composed of an inorganic core surrounded by a small molecule capping layer have been prepared, and, in some instances, described as protein-like. Proteins are both a benchmark and a source of inspiration for the design of those materials, which, ideally, will combine the distinct physical properties of inorganic nanoparticles with the remarkable (bio)chemical properties of proteins. Major differences remain, however, between proteins and these synthetic analogues. Proteins are nanoscale objects where the exact position of each residue, often critical to their function, is obtained through the use of template mRNA for the primary structure followed by non-covalent interactions, self-assembly and self-organization leading to the secondary, tertiary and quaternary structure. In contrast, the small molecules forming the organic capping layer of core-shell nanomaterials obtained to date tend to have an uncontrolled and often unknown structure at the molecular level.

While a number of attempts have been made to obtain biomimetic nanoparticles, designing, producing and characterising nanomaterials, which have an internal complexity analogous to proteins, remains a major challenge. In 2004, we have reported the rational and combinatorial design of peptides that bind to gold nanoparticle using the cysteine thiol side chain and form dense self-assembled monolayers (SAMs), increasing colloidal stability and providing a versatile means of functionalization. In recent unpublished work, we have shown using FTIR and NMR that the structure of those peptide SAMs can be tuned by varying the sequences and nanoparticle curvature.

The aim of this PhD project will be to design and characterize peptide-capped nanoparticles with further degrees of controls over their secondary and tertiary structures, borrowing structural elements from nature. The project will combine experimental and computational investigations in Liverpool and Singapore to build a clear picture of the structure of these nanomaterials.

Training:
Experimental:
Synthesis, functionalization and characterization of gold nanoparticles
Peptide self-assembly, FTIR, NMR, DLS, Chemical and photochemical cross-linking
Electron microscopy
Theoretical:
Computational chemistry