Doctor of Philosophy (PhD)
Self-assembled peptide amphiphiles (PAs) have gained significant attention in recent years due to their ability to form various supramolecular nanostructures with unique physical and chemical properties. These amphiphilic molecules consist of a hydrophobic tail and a peptide domain, allowing for the formation of nanoscale assemblies in aqueous environments. The PA supramolecular structures have a wide range of potential applications, including drug delivery, tissue engineering, and regenerative medicine.
By manipulating the driving forces (e.g., hydrophobic interactions, hydrogen bonds, and electrostatic interactions) involved in the self-assembly, researchers can tune the self- assembly properties (size, shape, stability, and surface character) and, consequently, the biological properties of PAs. Thus, our lab aims to develop novel PAs for biomedicine applications by combining organic chemistry with peptide material science. We made chemical modifications on different sections of the PA molecule (hydrophilic head and backbone) to control the involved non-covalent interactions and evaluated the changes in self-assembly behaviors. At last, we assessed the potential application of the customized PAs.
Chapter 1 gives an introduction about self-assembly, the mechanism and key parameters for PA’s assembly, and the main applications of PA nanostructures.
In Chapter 2, I introduce the concept of isosteric replacement to the PA system. A series of anionic PAs were designed to construct the fibrous shape at neutral pH. Five isosteres (sulfonic acid, phosphoric acid, methyl sulfonamide, methyl sulfonamide, trifluoromethyl sulfonamide, and cyanamide) were designed to replace the carboxylic acid iii of glutamic acid. Our data indicate that the isosteric replacement allows the pH control of supramolecular morphology by manipulating the pKa value of charged groups located on the nanostructure’s surface. Moreover, the stabilities of nanostructures towards high temperatures and concentrated salt are related to the morphology of assemblies and physicochemical characters of the headgroups.
In Chapter 3, we incorporated a urea group between the hydrophobic and hydrophilic domains of an aromatic PA system. This urea modification close to the core of PA assemblies has been demonstrated to enhance the stability against stimuli, including pH, temperature, and counterions. The urea modification also introduces disparate gelation properties with metal ions.
In Chapter 4, using the PA system designed in Chapter 3, we studied the differences in morphology and internal packing of PAs caused by the urea modification. The computational molecular simulation indicates that there is a 1.4-times increase of H-bonds per molecule with the urea modification, and the urea-π interaction influences the twisting of PA nanostructures. The resulting different characters enable urea-PA hydrogel to have better mechanical properties and the ability to support cells to attach and grow.
In Chapter 5, we applied the urea modification to various PA systems with different hydrophobic and hydrophilic sections. The stabilization effect of urea against environmental changes has been confirmed in all PA systems. For cationic PAs, the enhanced cohesion achieved from urea modification also alters the PA-membrane interaction.
In Chapter 6, the conclusion and future directions are described
Xing, Huihua, "Design, Synthesis, and Characterization of Peptide Amphiphile Biomaterials" (2023). Theses & Dissertations. 759.
Available for download on Tuesday, January 23, 2024