Ahamed Mir Jubair, Nasrin Tawfika, Rakhy Zarin Tasnim, Billah Md Masum, Karal Mohammad Abu Sayem
Department of Physics, Bangladesh University of Engineering and Technology, Dhaka 1000, Bangladesh.
Department of Physics, Jashore University of Science and Technology, Jashore 7408, Bangladesh.
Chem Phys Lipids. 2025 Sep;271:105525. doi: 10.1016/j.chemphyslip.2025.105525. Epub 2025 Jul 7.
Gramicidin A (GrA), a well-known ionophore, plays a significant role in modifying the biophysical properties of membranes. However, its mechanism of action in influencing rupture kinetics of vesicles and the stability of membranes under constant mechanical tension remains unclear. To investigate this, giant unilamellar vesicles (GUVs) composed of DOPG and DOPC phospholipids, with varying molar fractions of GrA (ranging from 0 % to 5 %), were synthesized using the natural swelling method. These GUVs were then subjected to mechanical tension using the micropipette aspiration technique. The rupture kinetics were assessed by quantifying the fraction of intact vesicles over time under a fixed mechanical tension, allowing the determination of the rupture rate constant. The results revealed a non-monotonic effect of GrA on membrane rupture: at low concentrations (up to 1 % GrA), GUVs exhibited increased structural stability, while at higher concentrations (1-5 % GrA), rupture probability significantly increased. Additionally, the area compressibility modulus of the GUV membranes was evaluated, showing that GrA incorporation led to alterations in membrane elasticity. These findings provide insights into the molecular mechanisms by which GrA modulates membrane integrity under mechanical stress, offering valuable implications for biophysical studies of ionophore-lipid interactions and membrane stability in biological systems.
短杆菌肽A（GrA）是一种著名的离子载体，在改变膜的生物物理性质方面发挥着重要作用。然而，其影响囊泡破裂动力学以及在恒定机械张力下膜稳定性的作用机制仍不清楚。为了研究这一点，使用自然膨胀法合成了由DOPG和DOPC磷脂组成、GrA摩尔分数不同（范围从0%到5%）的巨型单层囊泡（GUVs）。然后使用微量移液器抽吸技术对这些GUVs施加机械张力。通过在固定机械张力下随时间量化完整囊泡的比例来评估破裂动力学，从而确定破裂速率常数。结果显示GrA对膜破裂具有非单调效应：在低浓度（高达1% GrA）下，GUVs表现出结构稳定性增加，而在较高浓度（1 - 5% GrA）下，破裂概率显著增加。此外，还评估了GUV膜的面积压缩模量，结果表明掺入GrA会导致膜弹性发生变化。这些发现为GrA在机械应力下调节膜完整性的分子机制提供了见解，对离子载体 - 脂质相互作用和生物系统中膜稳定性的生物物理研究具有重要意义。
