Liu Jin, Ayyaswamy Portonovo S, Eckmann David M, Radhakrishnan Ravi
School of Mechanical and Materials Engineering, Washington State University.
Department of Mechanical Engineering and Applied Mechanics, University of Pennsylvania.
Heat Mass Transf. 2014 Mar 1;50(3):315-321. doi: 10.1007/s00231-013-1274-0.
We have developed a numerical model based on Metropolis Monte Carlo (MC) and the weighted histogram analysis method (WHAM) that enables the calculation of the absolute binding free energy between functionalized nanocarriers (NC) and endothelial cell (EC) surfaces. The binding affinities are calculated according to the free energy landscapes. The model predictions quantitatively agree with the analogous measurements of specific antibody coated NCs (100∼nm in diameter) to intracellular adhesion molecule-1 (ICAM-1) expressing EC surface in cell culture experiments. The model also enables an investigation of the effects of a broad range of parameters that include antibody surface coverage of NC, glycocalyx in both and conditions, shear flow and NC size. Using our model we explore the effects of shear flow and reproduce the shear-enhanced binding observed in equilibrium measurements in collagen-coated tube. Furthermore, our results indicate that the bond stiffness, representing the specific antibody-antigen interaction, significantly impacts the binding affinities. The predictive success of our computational protocol represents a sound quantitative approach for model driven design and optimization of functionalized nanocarriers in targeted vascular drug delivery.
我们基于 metropolis 蒙特卡洛（MC）和加权直方图分析方法（WHAM）开发了一个数值模型，该模型能够计算功能化纳米载体（NC）与内皮细胞（EC）表面之间的绝对结合自由能。结合亲和力根据自由能景观来计算。在细胞培养实验中，模型预测结果与特定抗体包被的 NC（直径 100∼nm）与表达细胞间黏附分子 -1（ICAM -1）的 EC 表面的类似测量结果在数量上一致。该模型还能够研究包括 NC 的抗体表面覆盖率、正常和炎症条件下的糖萼、剪切流以及 NC 大小等广泛参数的影响。使用我们的模型，我们探究了剪切流的影响，并重现了在胶原包被管的平衡测量中观察到的剪切增强结合。此外，我们的结果表明，代表特定抗体 - 抗原相互作用的键刚度对结合亲和力有显著影响。我们计算方案的预测成功代表了一种用于靶向血管药物递送中功能化纳米载体的模型驱动设计和优化的合理定量方法。
