细胞膜组分调控电穿孔的分子机制研究

doi:10.19586/j.2095-2341.2025.0081

生物技术进展 ›› 2025, Vol. 15 ›› Issue (6): 1057-1063.DOI: 10.19586/j.2095-2341.2025.0081

• 研究论文 • 上一篇

细胞膜组分调控电穿孔的分子机制研究

彭昱瑄¹(), 石铭芸¹^,², 蒋中英¹^,², 马晶¹^,²()

^1.伊犁师范大学网络安全与信息技术学院，微纳电传感技术与仿生器械重点实验室，新疆伊宁 835000
^2.伊犁师范大学网络安全与信息技术学院，伊犁智能计算研究与应用重点实验室，新疆伊宁 835000

收稿日期:2025-07-10 接受日期:2025-10-11 出版日期:2025-11-25 发布日期:2026-01-04
通讯作者: 马晶
作者简介:彭昱瑄E-mail: pengboshi2022@126.com；
基金资助:
国家自然科学基金项目(12364030);伊犁师范大学科研项目(2023YSWN02);伊犁师范大学校级重大项目(2023YSZD007);伊犁师范大学校级项目(CXZK2021011)

Molecular Mechanisms Underlying Membrane Composition-dependent Regulation of Electroporation

Yuxuan PENG¹(), Mingyun SHI¹^,², Zhongying JIANG¹^,², Jing MA¹^,²()

^1.Key Laboratory of Micro Nano Electric Sensing Technology and Bionic Instruments，School of Network Security and Information Technology，YiLi Normal University，Xinjiang Yining 835000，China
^2.Key Laboratory of YiLi Intelligent Computing Research and Application，School of Network Security and Information Technology，YiLi Normal University，Xinjiang Yining 835000，China

Received:2025-07-10 Accepted:2025-10-11 Online:2025-11-25 Published:2026-01-04
Contact: Jing MA

摘要/Abstract

摘要：

跨膜电位介导的电穿孔是生物医学应用中关键的物理过程，其中膜组分是重要的调控因素。运用全原子分子动力学（molecular dynamic, MD）模拟，探索了膜厚度、电位差离子对数和胆固醇含量对电位不平衡驱动的电穿孔的微观机制。结果表明，膜疏水核心厚度与电穿孔临界电位差呈线性正相关，1,2-二棕榈酰-sn-甘油-3-磷酸胆碱(1,2-Dipalmitoyl-sn-glycero-3-phosphocholine，DPPC)膜（3.30 nm）较1,2-二月桂酰-sn-甘油-3-磷酸胆碱(1,2-Dilauroyl-sn-glycero-3-phosphocholine，DLPC)膜（2.91 nm）临界电位差提高25%。膜内外离子对数量差增大可促使水孔尺寸扩大并加速离子转运。胆固醇通过增强脂质有序性与尾链序参数，提高膜刚性与成孔能垒。在高离子对差（8对）条件下，胆固醇可增强膜压缩模量从而加速了水孔形成，但同时显著缩短了水孔寿命。研究建立了膜厚度、胆固醇含量、跨膜电位3种因素调控电穿孔的定量模型，为靶向电穿孔治疗技术的设计提供了理论依据。

关键词: 电穿孔, 分子动力学模拟, 脂质膜, 胆固醇

Abstract:

Transmembrane potential-mediated electroporation is a critical physical process in biomedical applications， where membrane components serve as key regulatory factors. This study employed all-atom molecular dynamics （MD） simulations to explore the microscopic mechanisms of potential imbalance-driven electroporation， focusing on the effects of membrane thickness， transmembrane ion-pair number difference， and cholesterol content. The results demonstrated a linear positive correlation between the hydrophobic core thickness of the membrane and the critical transmembrane potential difference for electroporation： compared with DLPC bilayers （2.91 nm）， the critical potential difference of DPPC bilayers （3.30 nm） increased by 25%. An increase in the transmembrane ion-pair number difference promoted the expansion of aqueous pore size and accelerated ion transport. Cholesterol enhanced lipid ordering and acyl chain order parameters， thereby increasing membrane rigidity and elevating the energy barrier for pore formation. Under the condition of high ion-pair difference （8 pairs）， cholesterol could enhance the membrane compressibility modulus to accelerate aqueous pore formation， while significantly shortening the pore lifetime. These findings establish a quantitative model for the regulation of electroporation by three factors （membrane thickness， cholesterol content， and transmembrane potential）， providing a theoretical basis for the design of targeted electroporation therapeutic technologies.

Key words: electroporation, molecular dynamics simulation, lipid membrane, cholesterol

中图分类号:

Q241

彭昱瑄, 石铭芸, 蒋中英, 马晶. 细胞膜组分调控电穿孔的分子机制研究[J]. 生物技术进展, 2025, 15(6): 1057-1063.

Yuxuan PENG, Mingyun SHI, Zhongying JIANG, Jing MA. Molecular Mechanisms Underlying Membrane Composition-dependent Regulation of Electroporation[J]. Current Biotechnology, 2025, 15(6): 1057-1063.

图/表 5

表1 系统配置

Table 1 System configuration

模拟组	膜组分（单层）	膜外离子Na⁺/Cl^-	膜内离子Na⁺/Cl^-	电荷不平衡对数	运行时间/ns
A	DPPC×128	3/3	3/3	0	200
B	DPPC×128	3/0	0/3	3	400
C	DPPC×128	4/0	0/4	4	400
D	DPPC×128	12/4	4/12	8	200
E	DLPC×128	3/0	0/3	3	200
F	DMPC×128	3/0	0/3	3	400
G	DOPC×128	12/8	8/12	4	200
H	DOPC×128 CHOL×60	12/8	8/12	4	400
I	DOPC×128 CHOL×60	14/8	6/12	6	400
J	DOPC×128 CHOL×60	16/8	4/12	8	200

图1 DPPC系统电穿孔形成到关闭模拟快照A：0 ns；B：33 ns；C：37 ns；D：190 ns；E：电穿孔开启-关闭示意图。脂质绿色珠子、红白色珠子、灰色透明珠子分别代表磷酸基、水分子、脂质疏水链；蓝色和黄色珠子代表Cl-和Na+

Fig. 1 Sequential snapshots of electroporation dynamics (pore formation to resealing) in DPPC bilayers

图2 不同跨膜离子对差条件下DPPC膜的电穿孔行为A：0对离子跨膜电位差系统模拟快照；B：3对离子跨膜电位差系统模拟快照；C：8对离子跨膜电位差系统模拟快照。蓝色箭头表示沿Z轴膜电位方向；D：存在跨膜电位差的DPPC系统电势差随Z轴的变化，用P表示的绿色实现中的突起表示下双层中磷原子的平均位置；E：含有0对、3对离子跨膜膜电位差系统上双层外侧小叶最大局部膜曲率随模拟时间的变化

Fig. 2 Electroporation behavior of DPPC bilayers under different transmembrane ion-pair differences

图3 不同厚度脂质双分子层中跨膜电位驱动电穿孔的对比A：模拟E、F水孔形成时的快照；B：离子转运对数随模拟时间变化

Fig. 3 Comparison of transmembrane potential-driven electroporation across lipid bilayers of varying thickness

图4 胆固醇对DOPC膜电穿孔动力学的调控作用A：模拟G、H、I、J组的快照，胆固醇用粉色长链表示；B：上双层sn2链各个C的有序度（Smol）

Fig. 4 Regulatory effects of cholesterol on electroporation dynamics in DOPC bilayers

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细胞膜组分调控电穿孔的分子机制研究

Molecular Mechanisms Underlying Membrane Composition-dependent Regulation of Electroporation

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