Skakauskas Vladas, Katauskis Pranas, Skvortsov Alex, Gray Peter
Defence Science and Technology Organisation, 506 Lorimer st,, VIC 3207 Melbourne, Australia.
Theor Biol Med Model. 2014 Feb 13;11:11. doi: 10.1186/1742-4682-11-11.
The modelling framework is proposed to study protection properties of antibodies to neutralize the effects of the plant toxin (ricin). The present study extends our previous work by including (i) the model of intracellular transport of toxin to the Endoplasmic Reticulum and (ii) the model of the internalised antibodies (when antibody is delivered directly into the cytosol).
Simulation of the receptor-toxin-antibody interaction is implemented by solving the systems of PDEs (advection-diffusion models) or ODEs (rate models) for the underlying transport coupled with mass-action kinetics.
As the main application of the enhanced framework we present a comparative study of two kinds (external and internalised) of antibodies. This comparison is based on calculation of the non-dimensional protection factor using the same set of parameters (geometry, binding constants, initial concentrations of species, and total initial amount of the antibody).
This research will provide a framework for consistent evaluation and comparison of different types of antibodies for toxicological applications.
提出该建模框架以研究抗体中和植物毒素(蓖麻毒素)作用的保护特性。本研究通过纳入以下内容扩展了我们之前的工作:(i)毒素向内质网的细胞内转运模型,以及(ii)内化抗体模型(当抗体直接递送至细胞质溶胶时)。
通过求解与质量作用动力学耦合的基础转运的偏微分方程组(平流 - 扩散模型)或常微分方程组(速率模型)来实现受体 - 毒素 - 抗体相互作用的模拟。
作为增强框架的主要应用,我们对两种(外部和内化)抗体进行了比较研究。该比较基于使用相同参数集(几何形状、结合常数、物种的初始浓度以及抗体的总初始量)计算无量纲保护因子。
本研究将为毒理学应用中不同类型抗体的一致评估和比较提供一个框架。