MAPPING THE MORPHOLOGICAL LANDSCAPE AND DYNAMICS OF PEPTIDE-POLYMER AMPHIPHILES

Diblock oligomeric peptide-polymer amphiphiles (PPAs) are biohybrid materials that offer versatile functionality by integrating the sequence-dependent properties of peptides with the synthetic versatility of polymers. With the utility of various polymerization and covalent coupling techniques PPAs can incorporate a variety of peptide sequences and polymer chains of varying molecular weight, dispersity, and monomer composition. Despite their potential as biocompatible materials, the rational design of PPAs for assembly into multi-chain nanoparticles remains challenging due to the complex intra- and intermolecular interactions emanating from the polymer and peptide segments. To address this gap, a library of PPAs was synthesized and assembled, using a combination of electron microscopy and computational simulations to understand how altering the chemical composition of both the peptide and polymer blocks influences nanoparticle assembly. Chapter 2 describes how oligomer molecular weight and dispersity of ethyl acrylate oligomers along with peptide length, and charge density influence self-assembly. We observed that PPAs predominantly formed spheres rather than anisotropic particles. Oligomer molecular weight and peptide hydrophilicity dictated morphology, while dispersity and peptide charge affected particle size. Chapter 3 describes how the monomer composition of the PPA oligomer tail can be used to control nanoparticle size and morphology by using different assembly protocols. The appendices expand on the image analysis protocol used to characterize PPA nanoparticle size and morphology, biophysical characterization of assembled PPA nanoparticles, and the utility of reverse-phase high performance chromatography to fractionate PPAs to control average oligomer tail length and dispersity to potentially direct nanoparticle assembly.