Monte Carlo Modeling of Molecular Diffusion in Brain Extracellular Space

Diffusion of molecules in brain extracellular space (ECS) is controlled by two major factors: Geometry and extracellular matrix (ECM) interactions [1]. ECS geometry hinders free diffusion of molecules and ECM interacts through electrostatic, steric or viscous mechanisms with the diffusing molecules (Fig. 1). Geometrical hindrance causes a general reduction in free diffusion coefficient of all small molecules and exerts no specificity in interaction [2, 3]. In contrast, most ECM interactions relate to specific molecules and their characteristics. Here our objective was to identify the least number of parameters that can replicate ECM, in order to first explore a functional role for the matrix and second to study the way in which ECM and ECS geometry combine to affect molecular diffusion. We based our analysis on available data for two different molecules: Ca [4] and FGF-2 [5].