Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.
J Theor Biol. 2010 Jun 7;264(3):914-33. doi: 10.1016/j.jtbi.2010.03.028. Epub 2010 Mar 20.
A class of novel explicit analytic solutions for a system of n+1 coupled partial differential equations governing biomolecular mass transfer and reaction in living organisms are proposed, evaluated, and analyzed. The solution process uses Laplace and Hankel transforms and results in a recursive convolution of an exponentially scaled Gaussian with modified Bessel functions. The solution is developed for wide range of biomolecular binding kinetics from pure diffusion to multiple binding reactions. The proposed approach provides solutions for both Dirac and Gaussian laser beam (or fluorescence-labeled biomacromolecule) profiles during the course of a Fluorescence Recovery After Photobleaching (FRAP) experiment. We demonstrate that previous models are simplified forms of our theory for special cases. Model analysis indicates that at the early stages of the transport process, biomolecular dynamics is governed by pure diffusion. At large times, the dominant mass transfer process is effective diffusion. Analysis of the sensitivity equations, derived analytically and verified by finite difference differentiation, indicates that experimental biologists should use full space-time profile (instead of the averaged time series) obtained at the early stages of the fluorescence microscopy experiments to extract meaningful physiological information from the protocol. Such a small time frame requires improved bioinstrumentation relative to that in use today. Our mathematical analysis highlights several limitations of the FRAP protocol and provides strategies to improve it. The proposed model can be used to study biomolecular dynamics in molecular biology, targeted drug delivery in normal and cancerous tissues, motor-driven axonal transport in normal and abnormal nervous systems, kinetics of diffusion-controlled reactions between enzyme and substrate, and to validate numerical simulators of biological mass transport processes in vivo.
提出、评估和分析了一类用于描述活体内生物分子质量传递和反应的 n+1 个耦合偏微分方程系统的新型显式解析解。该解法使用拉普拉斯变换和汉克尔变换,得到一个指数缩放的高斯函数与修正贝塞尔函数的递归卷积。该解适用于从纯扩散到多种结合反应的广泛生物分子结合动力学。所提出的方法为荧光恢复后光漂白(FRAP)实验过程中的 Dirac 和高斯激光束(或荧光标记生物大分子)分布提供了解决方案。我们证明了以前的模型是我们理论的简化形式,适用于特殊情况。模型分析表明,在传输过程的早期阶段,生物分子动力学由纯扩散控制。在大时间尺度下,主要的质量传递过程是有效扩散。通过解析推导和有限差分微分验证的灵敏度方程分析表明,实验生物学家应该使用荧光显微镜实验早期获得的完整时空分布(而不是平均时间序列)来从方案中提取有意义的生理信息。这样的小时间框架相对于当前使用的生物仪器提出了更高的要求。我们的数学分析突出了 FRAP 方案的几个局限性,并提供了改进它的策略。所提出的模型可用于研究分子生物学中的生物分子动力学、正常和癌变组织中的靶向药物输送、正常和异常神经系统中的马达驱动轴突运输、酶与底物之间扩散控制反应的动力学,以及验证体内生物质量传递过程的数值模拟器。