Polyelectrolyte complexes present new opportunities for self-assembled soft matter. Factors determining whether the phase of the complex is solid or liquid remain unclear. Ionic polypeptides enable examination of the effects of stereochemistry on complex formation. Here we demonstrate that chirality determines the state of polyelectrolyte complexes, formed from mixing dilute solutions of oppositely charged polypeptides, via a combination of electrostatic and hydrogen-bonding interactions. Fluid complexes occur when at least one of the polypeptides in the mixture is racemic, which disrupts backbone hydrogen-bonding networks. Pairs of purely chiral polypeptides, of any sense, form compact, fibrillar solids with a β-sheet structure. Analogous behaviour occurs in micelles formed from polypeptide block copolymers with polyethylene oxide, where assembly into aggregates with either solid or fluid cores, and eventually into ordered phases at high concentrations, is possible. Chirality is an exploitable tool for manipulating material properties in polyelectrolyte complexation.

Complex coacervation was achieved by combining poly(allylamine) (PAH) or branched poly(ethylenimine) (PEI) with poly(acrylic acid) (PAA) and poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA). We systematically investigated the effects of stoichiometry, salt concentration, and pH. Ternary coacervates formed over a broader range of stoichiometries compared to the base PAA/PDMAEMA system. An enhanced resistance to salt, that is, resistance to dissolution of the complex with added salt, was observed for ternary coacervates. PEI-containing systems showed a considerable difference in salt resistance at pH 6−8 due to the dramatic change in charge density. This change was interpreted in the context of a theoretical treatment that relies on the Voorn−Overbeek model for free energy. Coacervate stability and viscoelastic behavior were affected by stoichiometry, salt, and pH. Ternary coacervates maintain the characteristics and tunability of typical binary coacervates, but the choice of the third component is important, as it significantly affects the response and material properties.

Reported is the ability of α-helical polypeptides to self-assemble with oppositely-charged polypeptides to form liquid complexes while maintaining their α-helical secondary structure. Coupling the α-helical polypeptide to a neutral, hydrophilic polymer and subsequent complexation enables the formation of nanoscale coacervate-core micelles. While previous reports on polypeptide complexation demonstrated a critical dependence of the nature of the complex (liquid versus solid) on chirality, the α-helical structure of the positively charged polypeptide prevents the formation of β-sheets, which would otherwise drive the assembly into a solid state, thereby, enabling coacervate formation between two chiral components. The higher charge density of the assembly, a result of the folding of the α-helical polypeptide, provides enhanced resistance to salts known to inhibit polypeptide complexation. The unique combination of properties of these materials can enhance the known potential of fluid polypeptide complexes for delivery of biologically relevant molecules.

Reported is the ability of a-helical polypeptides to self-assemble with oppositely-charged polypeptides to form liquid complexes while maintaining their a-helical secondary structure.C oupling the a-helical polypeptide to an eutral, hydrophilic polymer and subsequent complexation enables the formation of nanoscale coacervate-core micelles.W hile previous reports on polypeptide complexation demonstrated ac ritical dependence of the nature of the complex (liquid versus solid) on chirality,t he a-helical structure of the positively charged polypeptide prevents the formation of b-sheets,w hichw ould otherwise drive the assembly into as olid state,t hereby,e nabling coacervate formation between two chiral components.T he higher charge density of the assembly,aresult of the folding of the a-helical polypeptide, provides enhanced resistance to salts knownt oi nhibit polypeptide complexation. The unique combination of properties of these materials can enhance the knownp otential of fluid polypeptide complexes for delivery of biologically relevant molecules.

Traditionally, complex coacervation is regarded as a process whereby two oppositely charged polyelectrolytes self-assemble into spherical droplets. Here, we introduce the polyzwitterionic complex, “pZC”, formed by the liquid-liquid phase separation of a polyzwitterion and a polyelectrolyte, and elucidate a mechanism by which such complexes can assemble using theory and experimental evidence. This system exhibits orthogonal phase behavior-it remains intact in acidic conditions, but disassembles as the pH increases, a process governed by the acid-base equilibria of the constituent chains. We relate the observed phase behavior to physiological conditions within the gastrointestinal tract with a simulation of the gastroduodenal junction, and demonstrate using video microscopy the viability of polyzwitterionic coacervates as technologies for the pH-triggered release of cargo. Such a system is envisaged to tackle imminent problems of drug transport via the oral route and serve as a packaging solution to increase uptake efficiency.