Ordered assemblies of peptide nanoparticles with only positive charge

Abstract

Surface charge patchiness of different charge types can influence the solution behaviors of colloidal particles and globular proteins. Herein, coiled coil ‘bundlemer’ nanoparticles that display only a single type of surface charge (SC) are computationally designed to compare their solution behaviors to mixed charge-type (MC) counterparts with both positively and negatively charged side chains. Nematic and columnar liquid crystal phases were discovered in low concentrations of SC particles, indicative of particle end-to-end stacking into columns combined with lateral electrostatic repulsion between columns, while MC particles with the same net charge and particle shape produced only amorphous, soluble aggregates. Similarly, porous lattices are formed in mixtures of SC/MC particles of opposite charges, while MC/MC mixtures of opposite charges produce only amorphous aggregates. The lattice structure is inferred with a machine learning optimization approach. The differences between SC and MC particle behaviors directly show the importance of surface electrostatic patchiness. ☐ Further investigation revealed that single charge-type coiled coil (SC) ‘bundlemer’ peptides exhibit multiple liquid crystalline (LC) mesophases above a critical concentration, despite having a geometric shape that, individually, is unlikely to produce LC phases at any concentration. An interparticle end-to-end stacking model of SC bundlemers is proposed, analogous to short double-stranded DNA systems. In this work, nematic, columnar, and smectic phases were observed with changing ionic strength in aqueous solution. A coarse-grained simulation qualitatively illustrated phase transitions from isotropic to nematic to higher-order LC phases. Different LC forming critical concentrations were observed for various SC sequences, indicating the variations of stacking efficiency due to terminal amino acid residues. Through combined experimental observation and molecular dynamics simulation, multiple sequences were designed to investigate the impact of the residues at N- and C-termini. Strategic placement and amino acid choice allow control over stacking and consequent LC formation. The results showed that the conformational flexibility of the N-terminal region and the attractive interaction between C-terminal functionalities promote end to-end stacking between bundlemer particles and can be used to control the critical concentration needed for LC formation. This work exposes the relation between amino acid sequence and interparticle association of SC coiled coil bundlemer particles, highlighting the programmable nature of the coiled coil system.