Biomembrane Permeabilization: Statistics of Individual Leakage Events Harmonize the Interpretation of Vesicle Leakage

0485588 - ÚFCH JH 2019 RIV US eng J - Článek v odborném periodiku
Braun, S. - Pokorná, Šárka - Šachl, Radek - Hof, Martin - Heerklotz, H. - Hoernke, M.
Biomembrane Permeabilization: Statistics of Individual Leakage Events Harmonize the Interpretation of Vesicle Leakage.
ACS Nano. Roč. 12, č. 1 (2018), s. 813-819. ISSN 1936-0851. E-ISSN 1936-086X
Grant CEP: GA ČR GA17-03160S
Institucionální podpora: RVO:61388955
Klíčová slova: leakage * dye release * pore
Obor OECD: Physical chemistry
Impakt faktor: 13.903, rok: 2018

The mode of action of membrane-active molecules, such as
antimicrobial, anticancer, cell penetrating, and fusion peptides and their
synthetic mimics, transfection agents, drug permeation enhancers, and
biological signaling molecules (e.g., quorum sensing), involves either the
general or local destabilization of the target membrane or the formation
of defined, rather stable pores. Some effects aim at killing the cell, while
others need to be limited in space and time to avoid serious damage.
Biological tests reveal translocation of compounds and cell death but do
not provide a detailed, mechanistic, and quantitative understanding of the
modes of action and their molecular basis. Model membrane studies of
membrane leakage have been used for decades to tackle this issue, but
their interpretation in terms of biology has remained challenging and often quite limited. Here we compare two recent,
powerful protocols to study model membrane leakage: the microscopic detection of dye influx into giant liposomes and
time-correlated single photon counting experiments to characterize dye efflux from large unilamellar vesicles. A statistical
treatment of both data sets does not only harmonize apparent discrepancies but also makes us aware of principal issues that
have been confusing the interpretation of model membrane leakage data so far. Moreover, our study reveals a fundamental
difference between nano- and microscale systems that needs to be taken into account when conclusions about microscale
objects, such as cells, are drawn from nanoscale models.
Trvalý link: http://hdl.handle.net/11104/0280535