(403h) Uptake Selectivity of Nanoparticles with Patterned Surface Charges in Sequence Controlled Polyampholyte Coacervates

Intrinsically disordered proteins (IDPs) are rich in charged residues and lack ordered 3d structure. They play an important role in the formation of membraneless organelles (MLOs) through liquid-liquid phase separation (LLPS), in which the electrostatic correlation is shown to be one of the most important driving forces and the charge sequence of IDPs can dramatically affect the phase behavior. Unlike IDPs, globular proteins can fold into complicated 3d structures and expose their charged residues to the surface to form specific surface charge pattern. We use coarse-grained molecular dynamics simulations to study the role of surface charge pattern in the partitioning of globular proteins in MLOs. In our simulations, globular proteins are modeled by spherical nanoparticles with patterned surface charges, while MLOs are represented by sequence-controlled polyampholyte coacervates. The free energy landscape of a globular protein partitioning between two MLOs is calculated by umbrella sampling. We have shown that the MLO formed by blocky polyampholytes prefers to uptake globular proteins with patchy surface charge, while the MLO formed by random polyampholytes shows stronger affinity to globular proteins with alternating surface charge. Such "like dissolves like" behavior is consistent with the theoretical picture of the sequence/pattern-dependent electrostatic correlation.