Single Chain Nanoparticles as SImplified Models of Intrinsically Disordered Proteins in CompLex CoAceRvates

ongoing

The study of intrinsically disordered proteins (IDPs) in cellular environments is complicated by their complex structures and dynamics, leading to challenges in understanding the role of topology in crowded media. Single-chain nanoparticles (SCNPs) have emerged as simplified synthetic models of IDPs, allowing researchers to explore structural and dynamical behaviors without the interference of molecular interactions. Recent advancements in SCNP synthesis methods for biopolymers and polyelectrolytes present new opportunities to study topological effects in complex phases such as polyelectrolyte complex (PEC) coacervates, which are vital for understanding phase separation in intracellular membraneless organelles. The objective of this research is to use model polypeptide SCNPs to elucidate the effects of their topology on the structure and dynamics of PEC coacervates. We hypothesize that the self-coiled structures of SCNPs influence the stoichiometric distribution of polyion charges, thereby affecting the phase behavior and dynamics of PEC coacervates. Our specific aims include: (1) the synthesis and characterization of polyelectrolyte SCNPs with varying morphologies, (2) investigating the impact of SCNP topology on the local structure of PEC coacervates, and (3) exploring dynamic signatures associated with topologically distinct coacervate structures. Utilizing state-of-the-art techniques such as small-angle neutron scattering, wide-angle X-ray scattering, and neutron spin echo, this project aims to advance our understanding of the topological effects in coacervation and contribute to the broader knowledge of phase behavior in both synthetic and biological systems.