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Updated: Jan 18, 2026

A Fluorescence-based Assay of Phospholipid Scramblase Activity
Published on: September 20, 2016
Phospholipid Scramblases Remodel the Shape of Asymmetric Membranes
Marc Siggel1, Ramachandra M Bhaskara1, Gerhard Hummer1,2
1Department of Theoretical Biophysics , Max Planck Institute of Biophysics , Max-von-Laue Str. 3 , 60438 Frankfurt am Main , Germany.
Abstract:
The cell membrane and many organellar membranes are asymmetric and highly curved. In experiments, it is challenging to reconstitute and characterize membranes that differ in the lipid composition of their leaflets. Here we use molecular dynamics simulations to study the large-scale membrane shape changes associated with lipid shuttling between asymmetric leaflets. We exploit leaflet asymmetry to create a stable, near-spherical vesicle bud connected to a flat bilayer under periodic boundary conditions. Then we demonstrate how the lipid scramblase nhTMEM16 relaxes the lipid-number asymmetry. By mediating the flipping of lipids, this transmembrane protein dissipates the mechanochemical gradient between the leaflets and drives a large-scale membrane reorganization, converting the vesicle bud into a flat membrane. Our procedure to exploit bilayer asymmetry for simulations of highly curved membranes can be used to study the function of other lipid transporters and membrane-shaping proteins.
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