Modeling Ca2+ diffusion in brain extracellular space
CBN (Computational Biology and Neurocomputing) seminars
Thursday 22 August 2013
to 15:00 at
Padideh Kamali-Zare (Dept. Physiology and Neuroscience, New York University, Medical School)
Molecular diffusion in brain extracellular space (ECS) is primarily controlled by interactions with the geometry and the interstitial matrix. Both factors increase λ, the tortuosity, a measure of hindrance to diffusion where λ2 = D/D* with D the free diffusion coefficient and D* the effective diffusion coefficient in brain. Geometry lengthens diffusion paths or creates holdup in local voids of dead-spaces in the ECS and matrix interacts via specific binding reactions.
Previous experiments showed a reduction in Ca2+ diffusion via interactions with chondroitin sulfate, a component of the matrix. Here, we 1) modeled the combination of matrix and ECS geometry to determine how both factors interact to affect diffusion, and 2) studied the effect of matrix distribution.
Our simulations result in a λ~2 (i.e. D*=D/4) when geometrical hindrance and matrix interactions combine. This agrees with experimental measurements in brain slices, and shows that molecules that undergo interaction with matrix are more hindered than those which do not. Our model also shows that matrix localized to the voids can be as effective as when uniformly distributed, if the local concentration is elevated to maintain the average ECS concentration.