Electrostatically driven polymer self-assembly mechanisms are vastly underexplored compared to that of amphiphilic based assemblies, and yet offer unique opportunities for both encapsulation of charged therapeutics and controlled delivery via the tailoring of intermolecular interactions using pH and salt. This study investigates the effect of chirality on the resultant solid or liquid character of electrostatically self-assembled polyelectrolyte complexes formed from oppositely charged polypeptides. We demonstrate that the formation of dynamic, liquid polyelectrolyte complexes requires at least one racemic partner in order to disrupt backbone hydrogen bonding networks. Conversely, the use of homochiral polypeptides enables the collapse of the complexes into compact, fibrillar solids with a �-sheet structure. Molecular dynamics simulations support these results while enabling visualization of the molecular structure of these complexes. The ability to use polypeptide chirality as a means for controlling the liquid or solid character of the resultant polyelectrolyte complexes is a useful tool in developing new self-assembled materials based on polyelectrolyte complex formation without otherwise altering the chemical composition of the material.  For example, nanoscale stabilization of polyelectrolyte complex formation can be achieved by coupling the polyelectrolyte to a neutral yet hydrophilic block, forming nanometer-sized micelles with a polyelectrolyte complex core and a hydrophilic corona.  In this work, we characterize the structure and stability of these polypeptide based model micellar systems using static and dynamic light scattering, electron microscopy, circular dichroism and small angle x-ray scattering.  Additionally, we create polyelectrolyte complex micelles that contain therapeutically relevant charged molecules such as miRNA and peptides, specifically for the treatment of atherosclerotic lesions and cancer.  The modular nature of these assemblies enables the addition of a targeting ligand outside the corona of the micelle to increase the efficacy of delivering miRNA. Initial cell studies conducted with the different miRNA containing micelles will be discussed.

Chirality-selected phase transitions in ionic polypeptide complexes

248th National Meeting (2014)

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