The stretching of plasma membranes of cells and lipid bilayers of vesicles affects the physical properties of the membrane as well as the functions of proteins/peptides in the membranes. Here, we examined the effect of membrane tension on the rate constant of the transbilayer movement (kFF) of fluorescent probe-labeled lipids using a new method. Specifically, we recently reported [Hasan et al., Langmuir 34, 3349 (2018)] the development of a technique that employs giant unilamellar vesicles (GUVs) with asymmetric lipid compositions in two monolayers. In the present work, we found that the kFF greatly increased with tension without leakage of water-soluble fluorescent probes from the GUV lumen (i.e., without the formation of pores in the GUV membrane). We discussed the plausible mechanisms for the effect of tension on the transbilayer movement of lipids. As one of the mechanisms, we hypothesized that the transbilayer movement of lipids occurs through the lateral diffusion of lipids in the walls of hydrophilic pre-pores.

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