(457a) Molecular Engineering of Biomimetic Condensates and Polyelectrolyte Complex Micelles | AIChE

(457a) Molecular Engineering of Biomimetic Condensates and Polyelectrolyte Complex Micelles

Authors 

Leon, L. - Presenter, University of Central Florida
Biological condensates (membraneless organelles) are liquid droplets consisting of proteins and nucleic acids that form within cells and carefully regulate biochemical reactions. These droplets are dynamic, have been shown to coalesce within cells, and can form and dissipate in response to biological and environmental signals. Many condensates have multiphase structure where different cellular components are sequestered into different layers, each with their own function. Here we discuss designing synthetic condensates to regulate biochemical reactions outside of cells. The synthetic condensates are formed via complex coacervation of oppositely charged polypeptides. Complex coacervation is a liquid-liquid phase separation that occurs via enthalpic charge interactions and entropic effects from the release of counterions and hydration water. We have created a library of different polypeptide sequences that incorporate various charge patterns, hydrophobic amino acids, and aromatic amino acids in the sequence. In addition, our sequences incorporate different chiral patterns of amino acids that bias the formation of liquid complex coacervates by preventing hydrogen bonding between the polypeptides know to form solid polyelectrolyte complexes. With this library we aim to explore the effects on the stability, encapsulation selectivity, and materials properties of the coacervate phase. Moreover, we mix coacervate phases with different interfacial tensions to create multiphase droplets and explore their function as synthetic condensates.

Using molecular engineering, 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. Here we explore the potential of these micelles as delivery vehicles for charged molecules like proteins and nucleic acids. We characterize the polyelectrolyte complex micelles using scattering techniques and electron microscopy and explore the use of a thermosensitive neutral block on the structure and dynamics of the assemblies. Moreover, we evaluate the encapsulation of small and large molecules within the micelles as well as the role of phase behavior of the polyelectrolyte complex core on molecular exchange between micelles.