ABSTRACT
Self-assembled nanostructures such as those formed by peptide amphiphiles (PAs) are of great interest in biological and pharmacological applications. Herein, a simple and widely applicable chemical modification, a urea motif, was included in the PA's molecular structure to stabilize the nanostructures by virtue of intermolecular hydrogen bonds. Since the amino acid residue nearest to the lipid tail is the most relevant for stability, we decided to include the urea modification at that position. We prepared four groups of molecules (13 PAs in all), with varying levels of intermolecular cohesion, using amino acids with distinct ß-sheet promoting potential and/or containing hydrophobic tails of distinct lengths. Each subset contained one urea-modified PA and nonmodified PAs, all with the same peptide sequence. The varied responses of these PAs to variations in pH, temperature, counterions, and biologically related proteins were examined using microscopic, X-ray, spectrometric techniques, and molecular simulations. We found that the urea group contributes to the stabilization of the morphology and internal arrangement of the assemblies against environmental stimuli for all peptide sequences. In addition, microbiological and biological studies were performed with the cationic PAs. These assays reveal that the addition of urea linkages affects the PA-cell membrane interaction, showing the potential to increase the selectivity toward bacteria. Our data indicate that the urea motif can be used to tune the stability of a wide range of PA nanostructures, allowing flexibility on the biomaterial's design and opening a myriad of options for clinical therapies.
Subject(s)
Hydrogen Bonding , Urea , Urea/chemistry , Hydrophobic and Hydrophilic Interactions , Peptides/chemistry , Peptides/pharmacology , Nanostructures/chemistry , Surface-Active Agents/chemistryABSTRACT
Ordered nanoscale patterns have been observed by atomic force microscopy at graphene-water and graphite-water interfaces. The two dominant explanations for these patterns are that (i) they consist of self-assembled organic contaminants or (ii) they are dense layers formed from atmospheric gases (especially nitrogen). Here we apply molecular dynamics simulations to study the behavior of dinitrogen and possible organic contaminants at the graphene-water interface. Despite the high concentration of N2 in ambient air, we find that its expected occupancy at the graphene-water interface is quite low. Although dense (disordered) aggregates of dinitrogen have been observed in previous simulations, our results suggest that they are stable only in the presence of supersaturated aqueous N2 solutions and dissipate rapidly when they coexist with nitrogen gas near atmospheric pressure. On the other hand, although heavy alkanes are present at only trace concentrations (micrograms per cubic meter) in typical indoor air, we predict that such concentrations can be sufficient to form ordered monolayers that cover the graphene-water interface. For octadecane, grand canonical Monte Carlo suggests nucleation and growth of monolayers above an ambient concentration near 6 µg m-3, which is less than some literature values for indoor air. The thermodynamics of the formation of these alkane monolayers includes contributions from the hydration free-energy (unfavorable), the free-energy of adsorption to the graphene-water interface (highly favorable), and integration into the alkane monolayer phase (highly favorable). Furthermore, the peak-to-peak distances in AFM force profiles perpendicular to the interface (0.43-0.53 nm), agree with the distances calculated in simulations for overlayers of alkane-like molecules, but not for molecules such as N2, water, or aromatics. Taken together, these results suggest that ordered domains observed on graphene, graphite, and other hydrophobic materials in water are consistent with alkane-like molecules occupying the interface.
