Membrane Tension Inhibits Lipid Mixing by Increasing the Hemifusion Stalk Energy

Petr Shendrik, Gonen Golani, Raviv Dharan, Ulrich S. Schwarz, Raya Sorkin

Research output: Contribution to journalArticlepeer-review

Abstract

Fusion of biological membranes is fundamental in various physiological events. The fusion process involves several intermediate stages with energy barriers that are tightly dependent on the mechanical and physical properties of the system, one of which is membrane tension. As previously established, the late stages of fusion, including hemifusion diaphragm and pore expansions, are favored by membrane tension. However, a current understanding of how the energy barrier of earlier fusion stages is affected by membrane tension is lacking. Here, we apply a newly developed experimental approach combining micropipette-aspirated giant unilamellar vesicles and optically trapped membrane-coated beads, revealing that membrane tension inhibits lipid mixing. We show that lipid mixing is 6 times slower under a tension of 0.12 mN/m compared with tension-free membranes. Furthermore, using continuum elastic theory, we calculate the dependence of the hemifusion stalk formation energy on membrane tension and intermembrane distance and find the increase in the corresponding energy barrier to be 1.6 kBT in our setting, which can explain the increase in lipid mixing time delay. Finally, we show that tension can be a significant factor in the stalk energy if the pre-fusion intermembrane distance is on the order of several nanometers, while for membranes that are tightly docked, tension has a negligible effect.

Original languageEnglish
Pages (from-to)18942-18951
Number of pages10
JournalACS Nano
Volume17
Issue number19
DOIs
StatePublished - 10 Oct 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Published by American Chemical Society.

Keywords

  • continuum elasticity
  • membrane fusion
  • micropipette aspiration
  • optical tweezers
  • tension

ASJC Scopus subject areas

  • General Engineering
  • General Physics and Astronomy
  • General Materials Science

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