To Close or to Collapse: The Role of Charges on Membrane Stability upon Pore Formation

Autor: Rumiana Dimova, Rafael de Lira, Renan J. Melo, Fernanda S. C. Leomil, Karin A. Riske
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Advanced Science
bioRxiv
Advanced Science, Vol 8, Iss 11, Pp n/a-n/a (2021)
ISSN: 2198-3844
Popis: Resealing of membrane pores is crucial for cell survival. Membrane surface charge and medium composition are studied 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 strong electric pulse. Interestingly, charged vesicles appear 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. The observed findings in light of theories of stability and curvature generation are interpreted and mechanisms acting in cells to prevent total membrane collapse upon poration are discussed. Enhanced membrane stability is crucial for the success of electroporation‐based technologies for cancer treatment and gene transfer.
Leaky membranes cannot support life. Cells have developed protective mechanisms to respond to pore formation in their membranes. Here, charged lipids are shown to reduce pore edge tension and destabilize the membrane upon poration leading to catastrophic collapse. This membrane destabilization can be reverted by calcium ions, which points to ways for optimizing biotechnological developments employing electroporation for cancer treatment.
Databáze: OpenAIRE
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