Agent-based simulation of reactions in the crowded and structured intracellular environment: Influence of mobility and location of the reactants

While the co-localization of enzymes leads to faster reaction rates, the reduced mobility decreases the collision rate of reactants, hence reducing the reaction rate, as expected. This effect is most prominent in diffusion limited reactions. Furthermore, anomalous diffusion can occur due to molecular crowding in the cell. In the context of diffusion controlled reactions, anomalous diffusion leads to fractal reaction kinetics. The simulation framework is used to quantify and separate the effects originating from molecular crowding or the reduced mobility of the reactants. We were able to define three factors which describe the effective reaction rate, namely f diff for the diffusion effect, f volume for the crowding, and f access for the reduced accessibility of the molecules.Molecule distributions, reaction rate constants and structural parameters can be adjusted separately in the simulation allowing a comprehensive study of individual effects in the context of a realistic cell environment. As such, the present simulation can help to bridge the gap between in vivo and in vitro kinetics.The complex structured and crowded intracellular conditions [1] have a tremendous impact on intracellular reactions. Accordingly, the in vivo rate constants or even the structure of the kinetic rate expression can significantly differ from those obtained in in vitro assays [2]. First of all, the crowded conditions squeeze all molecules closer together which favors the formation of more compact complexes [3-5]. Associations or more general bimolecular reactions are governed by the occurrence of collisions of the respective molecules. The frequency of the collisions, in turn, depends on the mobility of the molecules. Molecular crowding and especially the cytoskeleton structure lead to a reduction in the diffusion rate, which depends on the size of the molecules [6]. Via the collision based principle of (diffusion-limited) reactions this also translates into reduced reaction rates [7,8].