Lele Tanmay P, Thodeti Charles K, Pendse Jay, Ingber Donald E
Department of Chemical Engineering, University of Florida, Gainesville, FL 32611, USA.
Biochem Biophys Res Commun. 2008 May 9;369(3):929-34. doi: 10.1016/j.bbrc.2008.02.137. Epub 2008 Mar 10.
The formation of focal adhesions governs cell shape and function; however, there are few measurements of the binding kinetics of focal adhesion proteins in living cells. Here, we used the fluorescence recovery after photobleaching (FRAP) technique, combined with mathematical modeling and scaling analysis to quantify dissociation kinetics of focal adhesion proteins in capillary endothelial cells. Novel experimental protocols based on mathematical analysis were developed to discern the rate-limiting step during FRAP. Values for the dissociation rate constant k(OFF) ranged over an order of magnitude from 0.009+/-0.001/s for talin to 0.102+/-0.010/s for FAK, indicating that talin is bound more strongly than other proteins in focal adhesions. Comparisons with in vitro measurements reveal that multiple focal adhesion proteins form a network of bonds, rather than binding in a pair-wise manner in these anchoring structures in living cells.
粘着斑的形成决定细胞形状和功能;然而,对活细胞中粘着斑蛋白结合动力学的测量却很少。在这里,我们使用光漂白后荧光恢复(FRAP)技术,结合数学建模和标度分析来量化毛细血管内皮细胞中粘着斑蛋白的解离动力学。基于数学分析开发了新的实验方案,以识别FRAP过程中的限速步骤。解离速率常数k(OFF)的值范围跨越一个数量级,从桩蛋白的0.009±0.001/s到粘着斑激酶的0.102±0.010/s,这表明桩蛋白在粘着斑中比其他蛋白结合得更紧密。与体外测量结果的比较表明,多种粘着斑蛋白形成一个键网络,而不是在活细胞的这些锚定结构中以两两结合的方式结合。