Quantifying kinetics of multi-protein self-assembly, remodeling, and disassembly

In the cell, multi-protein assemblies cannot persist forever and must ultimately disassemble through active or spontaneous processes. Protein assemblies involved in virion formation and clathrin-coat formation also appear to undergo dynamic remodelling which is critical for successful function. We show here using reaction-diffusion simulations how the kinetics of these assembly and disassembly processes can be sensitively tuned by the binding kinetics and cooperative interactions of the coat components and the molecules linking them to the membrane. We determine regimes where assembled structures can spontaneously remodel or disassemble. For stable structures, we then predict how enzymatic reactions can be exploited to locally destabilize links to the membrane and drive remodelling and disassembly. Using our recently developed NERDSS software, these models generate space and time-dependent predictions that can be compared directly with experiment. Our generalized computational methods can directly simulate a broad range of assembly processes at the cell-scale, providing a natural companion to quantitative cell biology.