Basic features of a cell electroporation model: illustrative behavior for two very different pulses.
Basic features of a cell electroporation model: illustrative behavior for two very different pulses.
复制标题
DOI：
10.1007/s00232-014-9699-z
复制
发表时间：
2014-12
影响因子：
2.4
通讯作者：
Weaver, James C.
中科院分区：
文献类型：
--
作者：
Son, Reuben S.;Smith, Kyle C.;Gowrishankar, Thiruvallur R.;Vernier, P. Thomas;Weaver, James C.
科学越来越多地涉及复杂的建模。在这里，我们描述了一个模型的细胞电穿孔，其中膜的性质是动态修改的穿孔。空间尺度范围从细胞膜厚度（5 nm）到典型的哺乳动物细胞半径（10 m），可以与理想化和实验脉冲波形一起使用。该模型由传统的被动组件和额外的主动组件代表非平衡过程。模型响应包括可测量的量：跨膜电压，膜电导，和溶质转运速率和代表性的“长”和“短”脉冲的量。长脉冲-1.5 kV/cm，100 s-演化出两个具有5 nm处的谷的孔亚群，其分离具有1.5和12 nm半径处的峰的亚群。这种脉冲被广泛用于生物研究、生物技术和医学，包括通过药物输送的癌症治疗和通过引起坏死的非热物理肿瘤消融。短脉冲-40 kV/cm，10 ns-产生80倍多的孔，都很小（3 nm; 1 nm峰值）。这些纳秒脉冲通过细胞凋亡消融肿瘤。我们证明了该模型的响应说明性的电气和穿孔行为，和钙黄绿素和propidium的运输。然后，我们确定扩展建模能力。MD的结构-功能结果可以允许基于其脂质组成对细胞膜带来响应特异性的外推。在脉冲之后，通过诸如细胞膨胀和脉冲诱导的化学反应等机制，可以在几秒到几分钟内包括孔隙能量景观的变化，这些机制缓慢地改变孔隙行为。本文的在线版本（doi：10.1007/s 00232 -014-9699-z）包含补充材料，可供授权用户使用。
Science increasingly involves complex modeling. Here we describe a model for cell electroporation in which membrane properties are dynamically modified by poration. Spatial scales range from cell membrane thickness (5 nm) to a typical mammalian cell radius (10 m), and can be used with idealized and experimental pulse waveforms. The model consists of traditional passive components and additional active components representing nonequilibrium processes. Model responses include measurable quantities: transmembrane voltage, membrane electrical conductance, and solute transport rates and amounts for the representative “long” and “short” pulses. The long pulse—1.5 kV/cm, 100 s—evolves two pore subpopulations with a valley at 5 nm, which separates the subpopulations that have peaks at 1.5 and 12 nm radius. Such pulses are widely used in biological research, biotechnology, and medicine, including cancer therapy by drug delivery and nonthermal physical tumor ablation by causing necrosis. The short pulse—40 kV/cm, 10 ns—creates 80-fold more pores, all small (3 nm; 1 nm peak). These nanosecond pulses ablate tumors by apoptosis. We demonstrate the model’s responses by illustrative electrical and poration behavior, and transport of calcein and propidium. We then identify extensions for expanding modeling capability. Structure-function results from MD can allow extrapolations that bring response specificity to cell membranes based on their lipid composition. After a pulse, changes in pore energy landscape can be included over seconds to minutes, by mechanisms such as cell swelling and pulse-induced chemical reactions that slowly alter pore behavior. The online version of this article (doi:10.1007/s00232-014-9699-z) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
3.4
作者：
DeBruin, KA;Krassowska, W
通讯作者：
Krassowska, W
影响因子：
2.8
作者：
Esser, Axel T.;Smith, Kyle C.;Weaver, James C.
通讯作者：
Weaver, James C.
影响因子：
2.8
作者：
Garcia, P. A.;Pancotto, T.;Davalos, R. V.
通讯作者：
Davalos, R. V.
影响因子：
11.2
作者：
Frandsen, Stine Krog;Gissel, Hanne;Gehl, Julie
通讯作者：
Gehl, Julie
影响因子：
3.4
作者：
Canatella, PJ;Karr, JF;Prausnitz, MR
通讯作者：
Prausnitz, MR