The role of Glycocalyx in nanocarrier-cell adhesion investigated using a thermodynamic model and Monte Carlo simulations
The role of Glycocalyx in nanocarrier-cell adhesion investigated using a thermodynamic model and Monte Carlo simulations
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DOI：
10.1021/jp074514x
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发表时间：
2007-11-01
影响因子：
3.7
通讯作者：
Radhakrishnan, Ravi
中科院分区：
文献类型：
--
作者：
Agrawal, Neeraj J.;Radhakrishnan, Ravi
我们提出了一个平衡模型，用于量化糖萼在介导功能化纳米载体与内皮细胞相互作用中的作用。在该模型中，纳米载体粘附由三个物理参数之间的相互作用控制，即糖萼阻力、受体的弯曲刚度和受体-配体键刚度。我们描述了一个基于几个独立的（基于单分子和细胞的）表征实验合理确定这些关键参数值的程序。使用我们的模型和参数值的独立推导以及蒙特卡罗模拟，我们描述了平衡状态下纳米载体与内皮细胞的结合。我们表明，我们可以通过对结合数据的零拟合来定量重现实验结合亲和力。此外，我们的模拟提供了纳米载体结合的多价性以及抗原聚集程度的定量描述。我们的研究确定了两个有趣的参数：糖萼抗性和抗原弯曲刚度，这两个参数都会减少纳米载体的结合并改变纳米载体结合常数对温度变化的敏感性。总的来说，我们的模型、参数估计、模拟和灵敏度分析有助于对纳米载体结合过程提供统一的分子和能量分析。
We present an equilibrium model for quantifying the effect of glycocalyx in mediating the interaction of functionalized nanocarriers with endothelial cells. In this model, nanocarrier adhesion is governed by the interplay between three physical parameters, namely, glycocalyx resistance, flexural rigidity of receptors, and receptor-ligand bond stiffness. We describe a procedure to rationally determine the values of these crucial parameters based on several independent (single molecule and cell-based) characterizing experiments. Using our model and independent derivation of the parameter values in conjunction with Monte Carlo simulations, we describe the binding of nanocarriers to endothelial cells at equilibrium. We show that we can quantitatively reproduce the experimental binding affinities with zero fitting to binding data. Additionally, our simulations provide quantitative descriptions for the multivalency in nanocarrier binding, as well as for the degree of clustering of antigens. Our study identifies two interesting parameters: glycocalyx resistance and antigen flexural rigidity, both of which reduce binding of nanocarriers and alter the sensitivity of the nanocarrier binding constant to change's in temperature. Collectively, our model, parameter estimations, simulations, and sensitivity analyses help provide unified molecular and energetic analyses of the nanocarrier binding process.