The effect of reactive-diffusion and dynamic loading on protein transport in biological tissues
讲座名称:
The effect of reactive-diffusion and dynamic loading on protein transport in biological tissues
讲座时间:
2014-06-27
讲座人:
Lihai Zhang
形式:
校区:
兴庆校区
实践学分:
讲座内容:
讲座题目:The effect of reactive-diffusion and dynamic loading on protein transport in biological tissues
讲座时间:2014年6月27日下午4:00-5:00
讲座地点:化学楼207会议室
讲座内容:
Solute transport plays an important role in transporting nutrients, such as Insulin-like growth factors (IGFs), into a biological tissue. Experiments on tissue engineered construct showed that dynamic loading at 1 Hz @ 10% strain leads to an increase of tissue construct aggregate modulus by nearly 100% while IGF-I alone increases aggregate modulus by 50%. Most importantly, the combination of IGF-I and dynamic loading synergistically increases the aggregate modulus as high as 250%. These research outcomes indicate that cells within a biological tissue exert their biological actions by responding not only to their biochemical but also biomechanical microenvironment.
For an avascular tissue, like cartilage, IGFs have to be transported into the tissue by diffusion, and so reach the chondrocytes to exert their biological actions. In the presence of dynamic loading, IGFs are transported by the fluid advection too. It is known that there are at least six IGF binding proteins modulating the bioavailability of IGFs in vivo. Our previous studies have theoretically shown that reversible binding between IGFs and IGFBPs provides an efficient symmetric breaking mechanism that enhances IGF transport into the tissue. Further, the combination of binding and cyclic loading leads to an increased enhancement. In addition, IGFBP-degrading proteases, such as matrix metalloproteases (MMPs), are capable of eliminating excess IGFBPs, cleaving IGFBP into fragments that bind IGFs with significantly low affinity. Recently, we have theoretically demonstrated that the selective degradation of IGFBPs can significantly concentration IGFs within the tissues.[4]. Physiological relevant loading can influence the homeostasis not only indirectly by enhancing the solute advective transport but also directly by acting as cellular mechanical stimuli. Our recent studies [5-7] suggested that chondrocyte mediated glycosaminoglycans (GAGs) synthesis depends on the dynamic loading induced interstitial fluid flow. Further, cellular response to mechanical stimuli exhibits a so called “threshold behaviour”, with GAG production only triggered when the interstitial fluid velocity exceeds a certain threshold (i.e. 0.25 m/s).
Furthermore, in tissue engineering, initial cell density selection and nutrient accessibility are important to cell growth or tissues. To make sure uniform tissue development, initial cell density needs to be carefully chosen. Our developed model would enable optimal selection of loading conditions and initial cell densities.
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