Control of Peptide Amphiphile Supramolecular Nanostructures by Isosteric Replacements

Abstract

Supramolecular nanostructures with tunable properties can have applications in medicine, pharmacy, and biotechnology. In this work, we show that the self-assembly behavior of peptide amphiphiles (PAs) can be effectively tuned by replacing the carboxylic acids exposed to the aqueous media with isosteres, functionalities that share key physical or chemical properties with another chemical group. Transmission electron microscopy, atomic force microscopy, and small-angle X-ray scattering studies indicated that the nanostructure’s morphologies are responsive to the ionization states of the side chains, which are related to their pK a values. Circular dichroism studies revealed the effect of the isosteres on the internal arrangement of the nanostructures. The interactions between diverse surfaces and the nanostructures and the effect of salt concentration and temperature were assessed to further understand the properties of these self-assembled systems. These results indicate that isosteric replacements allow the pH control of supramolecular morphology by manipulating the pK a of the charged groups located on the nanostructure’s surface. Theoretical studies were performed to understand the morphological transitions that the nanostructures underwent in response to pH changes, suggesting that the transitions result from alterations in the Coulomb forces between PA molecules. This work provides a strategy for designing biomaterials that can maintain or change behaviors based on the pH differences found within cells and tissues.

Urea-Modified Self-Assembling Peptide Amphiphiles That Form Well-Defined Nanostructures and Hydrogels for Biomedical Applications

“…All PAs were synthesized using standard Fmoc solid-phase peptide chemistry following our previous paper …”

“…All PAs were synthesized using standard Fmoc solid-phase peptide chemistry following our previous paper. 35 U was synthesized by coupling the peptide segment to a dodecyl isocyanate molecule (8 equiv) with DMSO/DMF = 1/1. The obtained molecules were purified and characterized as reported but with a solvent mixture of acetonitrile and water, both containing 0.1% ammonium.…”

“…The obtained molecules were purified and characterized as reported but with a solvent mixture of acetonitrile and water, both containing 0.1% ammonium. 35 The mass was confirmed by MALDI (Bruker Autoflex maX). The organic solvent was removed, and the samples were frozen and lyophilized (FreeZone, Labconco) after the pH was adjusted to 7.0 (0.1 M HCl and NaOH).…”

“…PA samples (1 mg/mL) were deposited on aminopropyl silatrane (APS) mica and scanned according to the protocol in our previous paper. 35 Transmission Electron Microscopy (TEM). The PAs were prepared to give a final concentration of 1 mg/mL and aged for the required time before the experiments.…”

“…The operation followed the protocol described in our previous work. 35 Small-Angle X-ray Scattering (SAXS). SAXS data were collected on BioSAXS/HP-Bio beamline ID7A at Cornell High-Energy Synchrotron Source (CHESS).…”