Molecular microdosimetry for electric fields

我们提出了分子微剂量学的生物效应，由于在多细胞结构中的弱和强电场的调查。一种新的模拟方法将用于预测物理量：等电位（电场），跨膜电压，电流密度和功率耗散密度（SAR）。预测的物理量将与三类生物物理机制（1）电压门控通道，（2）电穿孔和（3）通过局部加热改变生物化学过程）一起使用，以预测场诱导的分子变化、分子剂量（每个细胞的变化）和暴露阈值。 如初步工作所示，单个模拟/模型可以描述弱场和强场生物电行为。多细胞结构内的最大分子（化学）变化的网站将被估计为弱和强场。目标。我们将：（1）进一步发展新的多细胞结构生物电模拟方法，（2）发展分子微剂量学方法，（3）估计多细胞结构的分子剂量，（4）通过定量比较分子剂量与其他来源引起的分子变化，估计各种多细胞结构在弱场和强场下的暴露阈值。意义弱磁场：了解多细胞结构的分子变化阈值是评估50 - 60 Hz，RF和微波频率下可能的环境场效应的核心问题。强磁场：体内基于电穿孔的基因治疗、局部抗癌药物递送和电损伤具有弱场的共同特征：预期优先涉及特定组织区域。以前的工作。我们已经使用生物物理机制模型，分子变化估计和信噪比估计弱场阈值孤立的细胞和多细胞结构，和生物物理机制的电穿孔估计分子运输和摄取强场。方法.我们将使用已建立的生物物理机制模型和分子变化信噪比方法。新的模拟方法将在单CPU微处理器和（对于计算复杂性更高的问题）Beowulf计算机集群上运行。

We propose investigation of molecular microdosimetry for biological effects due to weak and strong electric fields in multicellular structures. A new simulation method will be used to predict physical quantities: equipotentials (electric fields), transmembrane voltages, current densities and power dissipation density (SAR). The predicted physical quantities will then be used with three classes of biophysical mechanism (1) voltage-gated channels, (2) electroporation and (3) alteration of biochemical processes by local heating) to predict field- induced molecular change, molecular dose (change per cell), and exposure thresholds. As demonstrated in preliminary work, a single simulation/model can describe both weak and strong field bioelectric behavior. The sites of maximum molecular (chemical) change within multicellular structures will be estimated for weak and strong fields. Aims. We will: (1) Further develop the new bioelectric simulation method for multicellular structures, (2) Develop a molecular microdosimetry approach, (3) Estimate molecular dose for multicellular structures, and (4) Estimate exposure thresholds for various multicellular structures for weak and strong fields by quantitatively comparing molecular dose to molecular change due to other sources. Significance. Weak fields: Understanding molecular change-based thresholds for multicellular structures is a central problem in assessing possible environmental field effects at 50 - 60 Hz, RF and microwave frequencies. Strong fields: In vivo electroporation-based gene therapy, localized anticancer drug delivery, and electrical injury share a common feature with weak fields: Particular tissue regions are expected to be preferentially involved. Previous Work. We have used biophysical mechanism models, molecular change estimates and signal-to-noise ratios to estimate weak field thresholds for isolated cells and multicellular structures, and the biophysical mechanism of electroporation to estimate molecular transport and uptake for strong fields. Methods. We will use established biophysical mechanism models and molecular change signal-to-noise ratio methods. The new simulation method will be run on single CPU microprocessors and (for problems with greater computational complexity) a Beowulf computer cluster.