Sequence-Dependent Kinetics of Polyampholyte Self-Assembly

We investigate the kinetics of self-assembly in solutions of polyampholytes (PAs) with identical net charge but differing charge sequences, using coarse-grained molecular dynamics simulations under moderately poor solvent conditions. Three representative sequence types─forming micelles with polyelectrolyte (PE) tails, micelles with sticky (telechelic) corona, and droplets─are studied to elucidate how charge patterning affects aggregate formation, stability, and dynamic restructuring. We identify three dominant mechanisms of mass redistribution: (1) direct binding and release of unimers, (2) merging of preassembled aggregates, and (3) bridging between cores via polyampholytic tails, which facilitates unimer exchange during inelastic collisions between larger aggregates. At low concentrations, a population of small aggregates forms that equilibrates easily through reversible association, whereas at higher concentrations, the kinetics are strongly influenced by sequence-dependent barriers and corona structures. Micelle-forming sequences exhibit kinetic trapping and minimal mass exchange, whereas droplet-forming sequences show frequent transitions and extended lifetimes of double-core aggregates. The interaction potential between aggregates is quantified and used to estimate association and dissociation times via a Fokker–Planck approach, in good agreement with simulation results. In addition, simulations of biologically relevant ProTα sequences reveal a dynamic gel-like network characterized by frequent unimer exchange. Our study highlights the crucial role of charge sequence in controlling the pathways of PA aggregation, offering insight into phase behavior in biological system and the design of functional polymeric materials.