Department of Civil and Environmental Engineering, The University of Melbourne, VIC 3010, Australia.
J Theor Biol. 2010 Mar 7;263(1):20-9. doi: 10.1016/j.jtbi.2009.11.023. Epub 2009 Dec 22.
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.
在这里，我们使用一个反应扩散传输模型来展示可扩散结合伴侣在分子向组织运输过程中的两个之前未被描述的功能作用。我们选择胰岛素样生长因子（IGF）及其结合伴侣 IGF 结合蛋白（IGFBP3）进入软骨作为一个特定组织的例子来证明一个普遍的原理。首先，我们表明游离蛋白（IGF）与其可扩散结合伴侣（游离 IGFBPs）之间的可逆结合可以增加蛋白质进入组织的速率。其次，结合伴侣的选择性降解可以增加组织中瞬态和稳态游离蛋白的浓度，使其远远高于源边界处的浓度，最大游离浓度出现在远离源边界的组织深部。这一发现与基于传统扩散分析的预期大相径庭。在软骨中，使用实际参数，这些新机制将组织深部的游离 IGF 浓度提高了一个数量级。由于游离蛋白的增加是由细胞“可调”的，我们的分析假设可以证明一个普遍的调节原理，它可能在全身的任何组织中起作用。
