Diffusion and advection in porous media as a model for transport of interstitial fluid in the brain.

Deposits of beta-amyloid (Aβ) proteins found in the brain are characteristics of neurological disorders such as Alzheimer’s disease and cerebral amyloid angiopathy. There is emerging evidence that the interstitial fluid (ISF) carrying soluble wastes such as Aβ proteins flows out of the brain through the basement membranes along the walls of cerebral arteries. The arterial wall is a porous medium consisting of muscle cells and extracellular matrix. The driving force for ISF flow within the arterial wall is hypothesized to come from arterial pulsations and low-frequency smooth muscle contraction waves, both of which lead to squeezing deformation of the porous medium. This results in the transport of the solutes in the porous basement membrane due to diffusion and forced advection. In our current work, we experimentally tested this hypothesis with a bench-top model to quantify the magnitudes of diffusion and directed advection in a porous microfluidic channel subjected to external squeezing forces. Type I collagen hydrogel was used as the porous medium to mimic the arterial basement membrane. Different squeezing conditions were achieved by varying the forcing wave magnitude, frequency, and direction. We present results for the transport velocities obtained through fluorescence imaging under the action of various forcing conditions.