Picosecond and Terahertz Perturbation of Interfacial Water and Electropermeabilization of Biological Membranes.

Nonthermal probing and stimulation with subnanosecond electric pulses and terahertz electromagnetic radiation may lead to new, minimally invasive diagnostic and therapeutic procedures and to methods for remote monitoring and analysis of biological systems, including plants, animals, and humans. To effectively engineer these still-emerging tools, we need an understanding of the biophysical mechanisms underlying the responses that have been reported to these novel stimuli. We show here that subnanosecond (≤ 500 ps) electric pulses induce action potentials in neurons and cause calcium transients in neuroblastoma-glioma hybrid cells, and we report complementary molecular dynamics simulations of phospholipid bilayers in electric fields in which membrane permeabilization occurs in less than 1 ns. Water dipoles in the interior of these model membranes respond in less than 1 ps to permeabilizing electric potentials by aligning in the direction of the field, and they re-orient at terahertz frequencies to field reversals. The mechanism for subnanosecond lipid electropore formation is similar to that observed on longer time scales — energy-minimizing intrusions of interfacial water into the membrane interior and subsequent reorganization of the bilayer into hydrophilic, conductive structures.

利用亚纳秒电脉冲和太赫兹电磁辐射进行非热探测和刺激可能会催生新的微创诊断和治疗方法，以及用于生物系统（包括植物、动物和人类）远程监测和分析的方法。为了有效地设计这些仍在不断涌现的工具，我们需要了解针对这些新型刺激所报道的反应背后的生物物理机制。我们在此表明，亚纳秒（≤500皮秒）电脉冲会在神经元中诱导动作电位，并在神经母细胞瘤 - 胶质瘤杂交细胞中引起钙瞬变，我们还报道了在电场中磷脂双层的互补分子动力学模拟，其中膜通透性在不到1纳秒内发生。这些模型膜内部的水分子偶极在不到1皮秒内通过沿电场方向排列对通透化电势作出响应，并且它们以太赫兹频率重新定向以适应电场反转。亚纳秒脂质电穿孔形成的机制与在较长时间尺度上观察到的机制相似——界面水以能量最小化的方式侵入膜内部，随后双层重新组织成亲水的导电结构。