Themed collection Structural and functional asymmetry of plasma membranes

Fusion of asymmetric membranes: the emergence of a preferred direction
The asymmetry in membrane lipid composition establishes a preferred direction for fusion. Here, we integrate theory and experiment to demonstrate that fusion initiated from opposite sides of an asymmetric membrane encounters distinct energy barriers.
Faraday Discuss., 2025, Advance Article
https://doi.org/10.1039/D4FD00189C

The interplay of composition and mechanics in the thermodynamics of asymmetric ternary lipid membranes
We propose a thermodynamic framework that describes the conditions for coexistence between the two leaflets of an asymmetric ternary lipid membrane comprising a saturated lipid, an unsaturated lipid, and cholesterol.
Faraday Discuss., 2025, Advance Article
https://doi.org/10.1039/D4FD00196F

Does plasma membrane transbilayer asymmetry coupled to lipid nanodomains drive fast kinetics of FGF2 membrane translocation into the extracellular space?
We hypothesize that transbilayer asymmetry of PI(4,5)P2 and other membrane lipids controls the thermodynamic properties of plasma membranes, governing the kinetics of FGF2 membrane translocation into the extracellular space.
Faraday Discuss., 2025, Advance Article
https://doi.org/10.1039/D4FD00208C

Phosphatidylserine affinity for and flip-flop dependence on Ca2+ and Mg2+ ions
Ca2+ ions are believed to play a crucial role in enzymatic regulation of lipid membrane asymmetry, yet direct effects of Ca2+ on lipid flip-flop are unknown. Present work examines the influence of Ca–lipid interactions on lipid translocation.
Faraday Discuss., 2025, Advance Article
https://doi.org/10.1039/D4FD00206G

Immune cell activation produces locally scrambled foci of plasma membrane lipids
We show that phosphatidylserine and phosphatidylethanolamine appear as transient foci on the plasma membrane external leaflet following immune receptor-mediated activation of mast cells.
Faraday Discuss., 2025, Advance Article
https://doi.org/10.1039/D4FD00205A

The influence of higher order geometric terms on the asymmetry and dynamics of membranes
Rapid shape changes of cells are facilitated by membrane viscosity and higher order geometric terms.
Faraday Discuss., 2025, Advance Article
https://doi.org/10.1039/D4FD00202D

Engineering of lipid membranes asymmetrically functionalized with chondroitin sulfate
A model system that mimics the glycocalyx: a lipid bilayer coated with chondroitin sulfate.
Faraday Discuss., 2025, Advance Article
https://doi.org/10.1039/D4FD00195H
Effect of a scramblase activator upon lipid and probe scrambling and membrane domain formation in HEK 293T cells
A model for how loss of asymmetry due to lipid scrambling may change membrane domain formation.
Faraday Discuss., 2025, Advance Article
https://doi.org/10.1039/D4FD00211C
Nonequilibrium asymmetry in the living cell membrane
We will discuss how sustained nonequilibrium processes operating at the plasma membrane (PM) determine the dynamical organisation (both lateral and transverse) of lipids, their maintenance and control, under physiological conditions.
Faraday Discuss., 2025, Advance Article
https://doi.org/10.1039/D4FD00207E
Elucidating the mechanical properties of asymmetric membranes by direct derivation of their energetics
Using all-atom MD simulations, we show that the biophysical properties of compositionally asymmetric POPC/DOPC bilayers are strongly correlated with the density imbalance between the leaflets.
Faraday Discuss., 2025, Advance Article
https://doi.org/10.1039/D5FD00006H

Melting point matters: designing lipid nanocarriers for improved T cell activation
We investigate the effect of the melting transition temperature of lipid nanocarriers on the activation efficiency of an immortalized line of T lymphocytes.
Faraday Discuss., 2025, Advance Article
https://doi.org/10.1039/D5FD00002E

Lipid–GPCR interactions in an asymmetric plasma membrane model
We report simulations and analysis of the A2A adenosine receptor in its fully active state, in two different membrane environments.
Faraday Discuss., 2025, Advance Article
https://doi.org/10.1039/D4FD00210E

Exploring the sensitivities of experimental techniques to various types of membrane asymmetry using atomistic simulations
We use atomistic simulations of lipid bilayers to generate representative datasets from model membranes in vitro, and examine the sensitivity of various experimental techniques to lipid abundance imbalances in compositionally asymmetric bilayers.
Faraday Discuss., 2025, Advance Article
https://doi.org/10.1039/D4FD00200H

Protein-induced membrane asymmetry modulates OMP folding kinetics and stability
Complementary charge matching between a protein-induced membrane dipole and a folding OMP leads to optimal folding kinetics and protein stability.
Faraday Discuss., 2025, Advance Article
https://doi.org/10.1039/D4FD00180J
Measuring the mechanical properties of asymmetric membranes in computer simulations – new methods and insights
We introduce a new Monte Carlo method to measure the elastic properties of ultra coarse-grained asymmetric membranes.
Faraday Discuss., 2025, Advance Article
https://doi.org/10.1039/D4FD00182F

Interaction of lipid domains originating from differential domain–monolayer contact energy
This work presents a theoretical model describing the interaction of lipid domains in apposed membrane monolayers, originating from differential contact energy, and predict conditions for domain attraction or repulsion.
Faraday Discuss., 2025, Advance Article
https://doi.org/10.1039/D4FD00186A

Asymmetric phase transitions in lipid bilayers: coupling or bending?
Asymmetric expansion of the leaflets of lipid-asymmetric vesicles due to the melting gel phases induces interleaflet coupling and/or vesicle budding.
Faraday Discuss., 2025, Advance Article
https://doi.org/10.1039/D5FD00003C
Asymmetric membrane properties through a protein lens
We investigate how well transmembrane domains of single-pass transmembrane proteins predict asymmetric membrane properties across the tree of life.
Faraday Discuss., 2025, Advance Article
https://doi.org/10.1039/D4FD00199K

The many faces of membrane tension for biomembranes and vesicles
We elucidate the many faces of membrane tension for biomimetic model membranes such as planar bilayers, nanovesicles, and giant vesicles. In all systems, each of the two leaflet tensions and the bilayer tension ∑ can be positive, zero, or negative.
Faraday Discuss., 2025, Advance Article
https://doi.org/10.1039/D4FD00184B

Spiers memorial lecture: Experimental discovery of asymmetric bilayers, and a recent asymmetry example
Asymmetric GUV of phase-separated Lo + Ld in one leaflet, dyed red, inducing domains in the other leaflet of DOPC/chol, dyed green.
Faraday Discuss., 2025, Advance Article
https://doi.org/10.1039/D5FD00041F

Characterization of lipid chain order and dynamics in asymmetric membranes by solid-state NMR spectroscopy
We studied the structure and dynamics of asymmetric POPCout/(POPE/POPG)in and POPSout/(POPE/POPG)in lipid membranes.
Faraday Discuss., 2025, Advance Article
https://doi.org/10.1039/D4FD00192C

Using phase-resolved vibrational sum-frequency imaging to probe the impact of head-group functionality on hierarchical domain structure in lipid membranes
State-of-the-art sum-frequency generation microscopy quantitatively reveals the heterogeneous changes in density, order, and composition from PS-lipid exposure in model membranes.
Faraday Discuss., 2025, Advance Article
https://doi.org/10.1039/D4FD00187G

Fabrication and characterization of phosphoinositide containing asymmetric vesicles in physiological salt conditions
Faraday Discuss., 2024, Accepted Manuscript
https://doi.org/10.1039/D4FD00191E

Membrane potential fluctuations and water asymmetry on plasma cell and model lipid membranes: origins, implications and properties
Faraday Discuss., 2024, Accepted Manuscript
https://doi.org/10.1039/D4FD00197D
About this collection
We are delighted to share with you a selection of the papers associated with a Faraday Discussion on Structural and functional asymmetry of plasma membranes. More information about the related event may be found here: http://rsc.li/membranes-fd2025. Additional articles will be added to the collection as they are published. The final versions of all the articles presented and a record of the discussions will be published after the event.
Recent developments in experimental and computational chemistry, physics and life sciences have enabled a greater quantitative understanding of lipid asymmetry and its coupling to protein function. This Discussion will explore the various facets of membrane asymmetry, bringing together experts in membrane physical chemistry, membrane biophysics, and membrane physiology.
On behalf of the organising committee, we look forward to welcoming you to London.