Radhakrishnan R, Uma B, Liu J, Ayyaswamy P S, Eckmann D M
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104.
J Comput Phys. 2013 Jul 1;244:252-263. doi: 10.1016/j.jcp.2012.10.026.
We present a fluctuating hydrodynamics approach and a hybrid approach combining fluctuating hydrodynamics with generalized Langevin dynamics to resolve the motion of a nanocarrier when subject to both hydrodynamic interactions and adhesive interactions. Specifically, using these approaches, we compute equilibrium probability distributions at constant temperature as well as velocity autocorrelation functions of the nanocarrier subject to thermal motion in a quiescent Newtonian fluid medium, when tethered by a harmonic spring force mimicking a tether due to a single receptor-ligand bond. We demonstrate that the thermal equipartition of translation, rotation, and spring degrees of freedom are preserved by our formalism while simultaneously resolving the nature of the hydrodynamic correlations. Additionally, we evaluate the potential of mean force (or free energy density) along a specified reaction coordinate to faciltate extensive conformational sampling of the nanocarrier motion. We show that our results are in excellent agreement with analytical results and Monte Carlo simulations, thereby validating our methodologies. The frameworks we have presented provide a comprehensive platform for temporal multiscale modeling of hydrodynamic and microscopic interactions mediating nanocarrier motion and adhesion in vascular targeted drug delivery.
我们提出了一种波动流体动力学方法以及一种将波动流体动力学与广义朗之万动力学相结合的混合方法，以解决纳米载体在受到流体动力学相互作用和粘附相互作用时的运动问题。具体而言，使用这些方法，我们计算了在恒温下的平衡概率分布以及纳米载体在静止牛顿流体介质中受热运动影响时的速度自相关函数，此时纳米载体由模拟单个受体 - 配体键所致系链的谐振弹簧力系住。我们证明，我们的形式体系保留了平移、旋转和弹簧自由度的热均分，同时解析了流体动力学相关性的本质。此外，我们沿着指定反应坐标评估平均力（或自由能密度）的势能，以促进纳米载体运动的广泛构象采样。我们表明，我们的结果与解析结果和蒙特卡罗模拟结果高度吻合，从而验证了我们的方法。我们提出的框架为介导纳米载体在血管靶向药物递送中的运动和粘附的流体动力学和微观相互作用的时间多尺度建模提供了一个综合平台。
