Figure 4.

Interaction of diffusing molecules with the extracellular matrix. (A) Shown here is the structure of the perineuronal net. Hyaluronan, secreted by membrane-bound HA synthase (HAS), binds to members of the lectican family (aggrecan, versican, neurocan, and brevican) and is cross-linked by link proteins and tenascin-R to form supramolecular aggregates on the surface of neurons (chondroitin sulfate-glycosaminoglycans, CS-GAGs). Graphic image is taken from Tsien (62) and derived from Kwok et al. (48) with permission of John Wiley & Sons. (B) Shown here is the diffusion of Ca²⁺ before (Control) (left curve, blue) and after CS glycan had been cleaved with chondroitinase ABC (chABC) (right curve, red) in rat cortical slice. Records were obtained with the RTP method, with time of injection marked by black dot in graphs. Plots are taken from Hrabětová et al. (54) with permission from John Wiley & Sons. (C) Shown here are diffusion measurements with the IOI method in vivo to measure interaction with HSPGs. Lactoferrin (Lf) or Lactoferrin + heparin (Lf + H) solutions were pressure-ejected from a micropipette at a depth of 200 μm in rat neocortex. The larger complex (Lf + H) diffused away more rapidly than the smaller Lf, indicating that the latter was binding to matrix components. Scale bar indicates 200 μm. Graphic panels are taken from Thorne et al. (55), copyright 2008 National Academy of Sciences. (D) Given here are the theoretical diffusion curves at 100 μm from source (Eq. 2, k′ = 0), showing effect of chABC on Ca²⁺ diffusion and comparison of diffusion of transferrin (no binding) and lactoferrin (binds to matrix). Note also the difference in diffusions times for the small Ca²⁺ ion compared to the larger proteins (∼80 kDa). Timescale is logarithmic. To see this figure in color, go online.