To close or to collapse: the role of charges on membrane stability upon pore formation

Published: Aug. 31, 2020, 7:01 p.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.31.274860v1?rss=1 Authors: Lira, R. B., Leomil, F. S. C., Melo, R. J., Riske, K. d. A., Dimova, R. Abstract: Resealing of membrane pores is crucial for cell survival. We studied the membrane surface charge and medium composition as defining regulators triggering bursting and collapse of giant unilamellar vesicles upon poration. The pores were generated by either electric field or a detergent. Vesicles composed of mixtures of zwitterionic and negatively charged lipids at varying molar ratios were subjected to a single strong electric pulse and their response was characterized for a given membrane and medium composition. We observe that charged vesicles are prone to catastrophic vesicle 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 molar fraction of charged lipids. Destabilization of charged vesicles upon pore formation is a universal process since 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 in charged membranes 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. Copy rights belong to original authors. Visit the link for more info