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.

We consider polyelectrolyte solutions which, under suitable conditions, phase separate into a liquid-like coacervate phase and a coexisting supernatant phase that exhibit an extremely low interfacial tension. Such interfacial tension provides the basis for most coacervate-based applications, but little is known about it, including its dependence on molecular weight, charge density, and salt concentration. By combining a Debye–Hückel treatment for electrostatic interactions with the Cahn–Hilliard theory, we derive explicit expressions for this interfacial tension. In the absence of added salts, we find that the interfacial tension scales as N –3/2(η/ηc–1)3/2 near the critical point of the demixing transition, and that it scales as η1/2 far away from it, where N is the chain length and η measures the electrostatic interaction strength as a function of temperature, dielectric constant, and charge density of the polyelectrolytes. For the case with added salts, we find that the interfacial tension scales with the salt concentration ψ as N –1/4(1−ψ/ψc)3/2 near the critical salt concentration ψc. Our predictions are shown to be in quantitative agreement with experiments and provide a means to design new materials based on polyelectrolyte complexation.

The aggregation of human amylin has been strongly implicated in the progression of Type II diabetes. This 37-residue peptide forms a variety of secondary structures, including random coils, α-helices, and β-hairpins. The balance between these structures depends on the chemical environment, making amylin an ideal candidate to examine inherent biases in force fields. Rat amylin differs from human amylin by only 6 residues; however, it does not form fibrils. Therefore it provides a useful complement to human amylin in studies of the key events along the aggregation pathway. In this work, the free energy of rat and human amylin was determined as a function of α-helix and β-hairpin content for the Gromos96 53a6, OPLS-AA/L, CHARMM22/CMAP, CHARMM22*, Amberff99sb*-ILDN, and Amberff03w force fields using advanced sampling techniques, specifically bias exchange metadynamics. This work represents a first systematic attempt to evaluate the conformations and the corresponding free energy of a large, clinically relevant disordered peptide in solution across force fields. The NMR chemical shifts of rIAPP were calculated for each of the force fields using their respective free energy maps, allowing us to quantitatively assess their predictions. We show that the predicted distribution of secondary structures is sensitive to the choice of force-field: Gromos53a6 is biased towards β-hairpins, while CHARMM22/CMAP predicts structures that are overly α-helical. OPLS-AA/L favors disordered structures. Amberff99sb*-ILDN, AmberFF03w and CHARMM22* provide the balance between secondary structures that is most consistent with available experimental data. In contrast to previous reports, our findings suggest that the equilibrium conformations of human and rat amylin are remarkably similar, but that subtle differences arise in transient alpha-helical and beta-strand containing structures that the human peptide can more readily adopt. We hypothesize that these transient states enable dynamic pathways that facilitate the formation of aggregates and, eventually, amyloid fibrils.

Polyelectrolyte molecules of opposite charge are known to form stable complexes in solution. Depending on the system conditions, such complexes can be solid or liquid. The latter are known as complex coacervates, and they appear as a second liquid phase in equilibrium with a polymer-dilute aqueous phase. This work considers the complexation between poly(glutamic acid) and poly(lysine), which is of particular interest because it enables examination of the role of chirality in ionic complexation, without changes to the overall chemical composition. Systematic atomic-level simulations are carried out for chains of poly(glutamic acid) and poly(lysine) with varying combinations of chirality along the backbone. Achiral chains form unstructured complexes. In contrast, homochiral chains lead to formation of stable β-sheets between molecules of opposite charge, and experiments indicate that β-sheet formation is correlated with the formation of solid precipitates. Changes in chirality along the peptide backbone are found to cause "kinks" in the β-sheets. These are energetically unfavorable and result in irregular structures that are more difficult to pack together. Taken together, these results provide new insights that may be of use for the development of simple yet strong bioinspired materials consisting of β-rich domains and amorphous regions.