Investigating the effects of molecular crowding on Ca2+ diffusion using a particle-based simulation model.
Calcium ions (Ca(2+)) are an important second messenger in eucaryotic cells. They are involved in numerous physiological processes which are triggered by calcium signals in the form of local release events, temporal oscillations, or reaction-diffusion waves. The diffusive spread of calcium signals in the cytosol is strongly affected by calcium-binding proteins (buffers). In addition, the cytosol contains a large number of inert molecules and molecular structures which make it a crowded environment. Here, we investigate the effects of such excluded volumes on calcium diffusion in the presence of different kinds of buffers. We find that the contributions in slowing down Ca(2+) diffusion coming from buffering and molecular crowding are not additive, i.e., the reduction in Ca(2+) diffusivity due to crowding and buffering together is not the sum of each single contribution. In the presence of Ca(2+) gradients and high affinity mobile buffers the effective diffusion coefficient of Ca(2+) can be reduced by up to 60% in highly crowded environments. This suggests that molecular crowding may significantly affect the shape of Ca(2+) microdomains and wave propagation in cell types with high excluded volume fractions.
Straube
Ronny
R
Max-Planck-Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany. rstraube@mpi-magdeburg.mpg.de
Ridgway
Douglas
D
D000465:Algorithms; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002118:Calcium / Q000737:chemistry*; D020013:Calcium Signaling; D003198:Computer Simulation; D004058:Diffusion; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000737:chemistry*; D008954:Models, Biological; D008956:Models, Chemical; D015233:Models, Statistical; D017711:Nonlinear Dynamics; D009991:Oscillometry / Q000379:methods*
D053496:Inositol 1,4,5-Trisphosphate Receptors; D002118:Calcium