On the role of diffusible binding partners in modulating the transport and concentration of proteins in tissues.

Here a reactive-diffusion transport model is used to demonstrate two previously undescribed functional roles for diffusible binding partners in the transport of molecules into tissues. The uptake of the insulin-like growth (IGF) and its binding partner the IGF binding protein (IGFBP3) into cartilage is used a specific tissue example to demonstrate a general principal. First, we show that reversible binding between free protein (IGF) and its diffusible binding partner (free IGFBPs) increases the rate of protein uptake into the tissue. Second, selective degradation of the binding partner can increase the transient and steady state free protein in tissues, well above the concentration at the source boundary, with the maximum free concentration occurring distant from the source boundary, deep within the tissue. This finding is very much at odds with expectations based on a traditional diffusion analysis. In cartilage, using realistic parameters, these new mechanisms raise the free IGF concentration by an order of magnitude deep within the tissue. As the increase in free protein is ‘tunable’ by cells, our analyses are postulated to demonstrate a general regulatory principle that may operate in any tissues throughout the body.