FRET-Based Determination of the Exchange Dynamics of Complex Coacervate Core Micelles

[Image: see text] Complex coacervate core micelles (C3Ms) are nanoscopic structures formed by charge interactions between oppositely charged macroions and used to encapsulate a wide variety of charged (bio)molecules. In most cases, C3Ms are in a dynamic equilibrium with their surroundings. Understanding the dynamics of molecular exchange reactions is essential as this determines the rate at which their cargo is exposed to the environment. Here, we study the molecular exchange in C3Ms by making use of Förster resonance energy transfer (FRET) and derive an analytical model to relate the experimentally observed increase in FRET efficiency to the underlying macromolecular exchange rates. We show that equilibrated C3Ms have a broad distribution of exchange rates. The overall exchange rate can be strongly increased by increasing the salt concentration. In contrast, changing the unlabeled homopolymer length does not affect the exchange of the labeled homopolymers and an increase in the micelle concentration only affects the FRET increase rate at low micelle concentrations. Together, these results suggest that the exchange of these equilibrated C3Ms occurs mainly by expulsion and insertion, where the rate-limiting step is the breaking of ionic bonds to expel the chains from the core. These are important insights to further improve the encapsulation efficiency of C3Ms.