Ramon Grima: "Elucidating the effects of compartmentation, mode of transport and crowding on intracellular reaction kinetics"

Dr. Ramon Grima
School of Biological Sciences, University of Edinburgh

Elucidating the effects of compartmentation, mode of transport and crowding on intracellular reaction kinetics

Classical descriptions of chemical kinetics ignore the physical nature of the intracellular environment. Some of the main implicit assumptions behind such approaches are: (i) reactions occur in compartment volumes which are large enough so that molecular discreteness can be ignored;

(ii) the environment is well-mixed via diffusion. Though these conditions are frequently met in laboratory conditions, it is not characteristic of the intracellular environment, which is compartmentalized at the micron and submicron scales, is highly crowded and transport may occur via active means of transport rather than diffusion. We develop a stochastic microscopic theory of enzyme-mediated and polymerization reactions in such an environment.

The method accurately captures the deviations from classical deterministic kinetics. In particular we find that:

(i) the classical enzyme kinetic equations do not correctly describe kinetics in intracellular compartments smaller than approximately 200nm, deviations being particularly pronounced if substrate transport to compartments is mediated by vesicle or granule transport and in the presence of competitive inhibitors;

(ii) noise due to the low copy number of molecules can considerably alter the shape of the frequency distribution of polymers in a compartment;

(iii) crowding can decrease the magnitude of intrinsic noise whilst making it more "coloured".