Aggregation phenomena in a system of molecules with two internal states

A model for the aggregation of molecules with two internal states is studied by kinetic Monte Carlo simulations. Molecules are represented by simple beads, discarding all stereochemical specificity. Monomers are placed in a three-dimensional lattice and diffusion processes are simulated, as well as internal state conversions of the molecules. The two internal states feature a stable (S) not assembly competent configuration, and an unstable assembly competent (A) configuration. Monomers in A state are given a higher energy if isolated, but they can reach the lowest energy level through short-range interactions between each other, so that their aggregation is promoted. Kinetics of cluster formation are examined, as well as the basic mechanisms ruling growth in our system. The simulations show that the aggregation process is preceded by a lag phase, which is followed by a fast growth phase. The duration of the lag phase is determined by the strength of the A-A interaction, whereas the time slope of the growth phase is mainly influenced by the conversion rate between internal states. The whole work has been inspired by the biological problem of amyloid aggregation, whose aggregation curves often present a sigmoidal behavior which is reproduced by the present model.