Coupling between heparan sulfate proteoglycans and FGF-2 receptors is key to FGF-2 capture under flow: A computational study

Bioavailability of regulatory molecules such as growth factors or cytokines is tightly controlled in vivo. Measurement of these molecules in circulation is difficult, especially within the cell microenvironment, and static tissue culture studies, although valuable, cannot mimic the conditions present in blood vessels with regard to the architecture or flow dynamics. Using endothelial-lined synthetic capillaries, we measured the capture of fibroblast growth factor-2 (FGF-2) and found that capture was critically dependent on the flow rate and the presence of heparan sulfate proteoglycans (HSPG). We developed a computational model as an aid to our experimental work and the model predictions compared well to experimental results both with and without HSPG. Simulations indicated that FGF-2 binding primarily occurred in the initial quarter of the bioreactor with much lower levels found further down the capillary due to depletion of FGF-2 near the capillary wall. Stability afforded by coupling between HSPG and FGF receptors was shown to play a dominant role in the process. Inclusion of fluid flow within our model provides an important step forward in studying growth factor dynamics and our model, coupled with our experimental bioreactor, has potential as a screening and predictive tool for investigating cellular activity within the microvasculature.