Understanding Sequence Effects in Coacervation and Protein Uptake

Complex coacervates serve as a versatile material platform, enabling a wide range of biochemical and biomedical applications, including biosensors, catalysts, and refrigeration-free vaccines. Studying coacervates has emerged as a valuable strategy for understanding fundamental aspects of self-assembly in biological condensates. These coacervates arise from the associative phase separation of oppositely charged polymers, a process primarily governed by electrostatic interactions and entropy-driven complexation. In this study, we design and synthesize a variety of sequence-specific peptides as model polymers and employ a panel of model proteins with different net charge and charge distributions to investigate the influence of sequence, hydrophobicity and protein encapsulation in our coacervates. While significant progress has been made in characterizing this phase separation, a deeper understanding of how polymer chemistry influences this process is still required. Our research takes a systematic and practical approach to integrating sequence-dependent effects into the physical understanding of complex coacervates, thereby expanding the range of chemical functionalities explored in peptide-based systems.