A Self‐Assembling Two‐Dimensional Protein Array is a Versatile Platform for the Assembly of Multicomponent Nanostructures

Abstract

Rationally designed two-dimensional (2D) arrays that support the assembly of nanoscale components are of interest for catalysis, sensing, and biomedical applications. The computational redesign of a protein called TTM that undergoes calcium-induced self-assembly into nanostructured lattices capable of growing to dozens of micrometers are previously reported. The work demonstrates here that the N- and C-termini of the constituent monomers are solvent-accessible and that they can be modified with a hexahistidine extension, a gold-binding peptide, or a biotinylation tag to decorate nickel-nitriloacetic acid beads with self-assembled protein islands, conjugate gold nanoparticles to planar arrays, or control the immobilization density of avidin molecules onto 2D lattices through co-polymerization of biotinylated and wild type TTM monomers. These results showcase the potential of TTM as a versatile 2D scaffold for the fabrication of hierarchical structures comprising a broad range of nanoscale elements.

Supramolecular Self-Assembly To Control Structural and Biological Properties of Multicomponent Hydrogels

“…In contrast, multicomponent self-assembly offers the possibility to generate a wider range of more complex structures, enhance modularity, and provide spatiotemporal control of self-assembly. 2,11 This approach has been used to harness synergistic properties as a result of using two different interacting molecular building blocks such as peptide–peptide, 12−14 protein–peptide, 15−17 PA–polysaccharide, 18 protein–protein, 19,20 and protein/peptide–DNA. 21 The structures and properties emerging from these systems are opening new opportunities for the rational design of more complex and functional materials.…”

De NovoDesigned Peptide and Protein Hairpins Self-assemble into Sheets and Nanoparticles

“…Specifically, the proximal pin allows splaying of the helical termini, which in turn leads to curved arrays that can close, whereas the distal pins give a more tightly constrained hairpin structure, consistent with building blocks required to make flat sheets. As noted earlier, others have developed similar self-assembling peptide and protein based nanoparticles [22][23][24][25][26][27][28][29][30] or sheets, [12][13][14][15][16][17][18] so what are the differences and advantages to our hairpin system? First, by including two points (loop and pin) that define the relative positions and rotational freedom of the two coiled-coil components, we are able to control the topology of the self-assembled structures by design in a single system to render closed nanoparticles or extended sheets.…”

“…10 The toolbox of useful self-assembling protein structures has been expanded by either mutating natural protein interfaces to induce controlled self-assembly, or by de novo design. 11 Such structures are usually computationally driven towards forming closely packed 2D arrays [12][13][14][15][16][17][18] , tubes [19][20][21] or 3D icosahedral particles. [22][23][24][25][26][27][28][29][30] However, these beautifully ordered near crystalline assemblies may not be amenable to decoration with large cargos, or be very permeable to small molecules due to their close packed nature.…”

Enzyme-Directed Functionalization of Designed, Two-Dimensional Protein Lattices

“…While a number of these strategies have been employed to generate extended 2D arrays with crystalline order, there has been little exploration thus far in using these arrays as functional platforms. 40,41 Interfacing chemical/ biological conjugation tools with such ordered assemblies would allow for the facile incorporation of functionality onto crystalline substrates. In this work, we used two crystalline assemblies previously designed in our lab, RIDC3 and C98 RhuA, as 2D platforms whose surfaces can be tagged with functional peptides as recognition elements to allow enzymemediated modification.…”