The Effects of Chirality and Salt Addition on Phase Separation and Complexation Morphology in Mixtures of Polypeptides and Polypeptoids.

Abstract

Liquid-liquid phase separation (LLPS), particularly through coacervation, offers a groundbreaking approach to drug delivery by encapsulating therapeutic agents within phase-separated droplets, enhancing their stability, solubility, and controlled release. Polypeptides and polypeptoids, with their structural diversity and tunability, emerge as promising candidates for exploring these systems, with polypeptoids offering unique advantages, such as resistance to enzymatic degradation and increased control over interactions. This study examines the impact of chirality, mixing charge fraction, and salt concentration on the phase behavior and morphology of homochiral, mixed-chiral, and achiral polymers. By exploring the role of chirality and ionic strength in determining the presence and morphology of complexation, this research provides critical insights for designing tunable coacervate systems. Our results show that polypeptides and polypeptoids demonstrate chirality-dependent complexation. Additionally, we show that the presence and morphology of phase separation within these systems are influenced by the concentration of charged species in each sample, enabling the control and tunability of complex formation. These findings have the potential to advance the development of biomaterials for applications ranging from gene therapy to vaccine stabilization, offering innovative solutions to pressing biomedical challenges.