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Atomic Force Microscopy Imaging and Force Spectroscopy of Supported Lipid Bilayers
Published on: July 22, 2015
Lipid-Substrate Interactions Lead to Bilayer Asymmetry
Ruofei Wang1, Ella Gregory1, Brandon A Oswald1
1Department of Chemistry, Penn State University, University Park, Pennsylvania 16802, United States.
Journal of the American Chemical Society
|May 12, 2026
Summary
Hydrogen bonding drives lipid asymmetry in supported lipid bilayers, mirroring cell membranes. Phosphatidylserine and phosphatidylethanolamine preferentially partition to the lower leaflet, influenced by surface interactions.
Area of Science:
- Biophysics
- Materials Science
- Cell Biology
Background:
- Cell membranes exhibit lipid asymmetry, with specific lipids enriched in inner or outer leaflets.
- Supported lipid bilayers (SLBs) are model systems to study membrane properties.
- Understanding lipid distribution is crucial for membrane function and cellular processes.
Purpose of the Study:
- To investigate the factors governing lipid asymmetry in SLBs.
- To determine the role of hydrogen bonding in lipid leaflet distribution.
- To compare lipid asymmetry in SLBs with that in cellular plasma membranes.
Main Methods:
- Formation of SLBs on planar glass and protein-coated substrates via vesicle fusion.
- Quantification of leaflet distribution using fluorescence microscopy and bilayer unzipping.
- Utilizing tail-labeled lipid probes (phosphatidylserine, phosphatidylethanolamine, phosphatidylcholine) to track distribution.
Main Results:
- Phosphatidylserine (PS) and phosphatidylethanolamine (PE) preferentially partitioned to the lower leaflet (75%) of SLBs.
- This partitioning was enhanced in D2O, indicating strong hydrogen bond formation with the substrate.
- Hydrogen bonding was the dominant factor, outweighing salt concentration effects.
- Phosphatidylcholine (PC) showed no leaflet preference as it could not hydrogen bond with the surface.
- 2D diffusion of PS and PE was dependent on available surface hydrogen bonding sites.
Conclusions:
- Hydrogen bonding between lipid headgroups and substrate silanols dictates lipid asymmetry in SLBs.
- The observed lipid distribution in SLBs mimics the asymmetry found in cellular plasma membranes.
- Surface hydrogen-bonding environments may be a key factor in establishing and maintaining lipid asymmetry in vivo.
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