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To close or to collapse: the role of charges on membrane stability upon pore formation
bioRxiv - Biophysics Pub Date : 2020-10-27 , DOI: 10.1101/2020.08.31.274860
Rafael B. Lira , Fernanda S. C. Leomil , Renan J. Melo , Karin A. Riske , Rumiana Dimova

Resealing of membrane pores is crucial for cell survival. We study membrane surface charge and medium composition as defining regulators of membrane stability. Pores are generated by electric field or detergents. Giant vesicles composed of zwitterionic and negatively charged lipids mixed at varying ratios are subjected to a single strong electric pulse. Charged vesicles are prone to catastrophic collapse transforming them into tubular structures. The spectrum of destabilization responses includes the generation of long-living submicroscopic pores and partial vesicle bursting. The origin of these phenomena is related to the membrane edge tension, which governs pore closure. This edge tension significantly decreases as a function of the fraction of charged lipids. Destabilization of charged vesicles upon pore formation is universal - it is also observed with other poration stimuli. Disruption propensity is enhanced for membranes made of lipids with higher degree of unsaturation. It can be reversed by screening membrane charge in the presence of calcium ions. We interpret the observed findings in light of theories of stability and curvature generation and discuss mechanisms acting in cells to prevent total membrane collapse upon poration. Enhanced membrane stability is crucial for the success of electroporation-based technologies for cancer treatment and gene transfer.

中文翻译:

闭合或坍塌:孔形成时电荷对膜稳定性的作用

膜孔的重新密封对于细胞存活至关重要。我们研究膜表面电荷和介质组成作为膜稳定性的调节剂。电场或清洁剂会产生毛孔。由以不同比例混合的两性离子和带负电荷的脂质组成的大囊泡会受到单个强电脉冲的作用。带电的囊泡易于发生灾难性崩溃,从而将其转变为管状结构。不稳定反应的范围包括长寿命亚显微孔的产生和部分囊泡破裂。这些现象的起源与控制孔封闭的膜边缘张力有关。该边缘张力根据带电脂质的分数而显着降低。带电囊泡在形成孔时不稳定,这是普遍现象-在其他刺激刺激下也观察到。由具有较高不饱和度的脂质制成的膜的破裂倾向增强。可以通过在钙离子存在下筛选膜电荷来逆转。我们根据稳定性和曲率产生的理论来解释观察到的发现,并讨论在细胞中起作用以防止渗透后总膜塌陷的机制。增强的膜稳定性对于基于电穿孔的癌症治疗和基因转移技术的成功至关重要。我们根据稳定性和曲率产生的理论来解释观察到的发现,并讨论在细胞中起作用以防止渗透后总膜塌陷的机制。增强的膜稳定性对于基于电穿孔的癌症治疗和基因转移技术的成功至关重要。我们根据稳定性和曲率产生的理论来解释观察到的发现,并讨论在细胞中起作用以防止渗透后总膜塌陷的机制。增强的膜稳定性对于基于电穿孔的癌症治疗和基因转移技术的成功至关重要。
更新日期:2020-10-30
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