Competition of folding-induced assembly and liquid-liquid phase separation produces diverse morphologies of peptide coacervates*

Competition between short-range hydrogen-bonding driven intramolecular assembly coupled with long-range colloidal phase instability dictated by electrostatics can result in protein misfolding that has been linked to many neurodegenerative diseases. Specifically, during charge condensation of peptide mixtures such as polylysine and polyglutamic acid of the same chirality, a competition between complex coacervation and beta sheet assembly gives rise to a diversity of structures in solution spanning solid precipitates to network-like bicontinuous structures to liquid-like coacervate droplets. Our investigation into this system indicate that while precipitates dominate at higher peptide concentrations and coacervates dominate at lower peptide concentrations, this competition is highly dependent on the processing of the mixture (including mixing path and thermal history). This complex phase behavior suggests a competition between hydrogen bonding driven beta sheet assembly and electrostatics driven coacervate formation; the new results and its implications for protein folding and assembly will be discussed in this talk.