The Dynamic Membrane State: From Lipid Composition and Biophysical Organization to Cellular Function

Dear Colleagues,

Cellular membranes are frequently introduced as lipid bilayers that delimit compartments and provide a matrix for proteins. This description is correct but incomplete. Membrane lipids are chemically diverse, spatially asymmetric, laterally organized, and continuously remodeled. Their headgroups, acyl or isoprenoid chains, linkage chemistry, stereochemistry, and relative abundance jointly determine bilayer thickness, curvature, lateral pressure, elasticity, permeability, electrostatic and dipole potentials, hydration, phase behavior, and domain formation. These physical properties, in turn, influence membrane–protein conformation, transport, signaling, organelle identity, energy conversion, stress adaptation, and cell–environment communication.

This Special Issue will introduce the dynamic membrane state as a unifying concept. The term will be used operationally and multidimensionally, rather than as a single scalar quantity. It denotes the measurable configuration that emerges from lipid molecular composition, leaflet asymmetry, lateral organization, phase state, curvature, thickness, mechanical moduli, electrostatics, hydration, and lipid–protein coupling at a defined time and biological scale. The central goal is to move beyond static lipid inventories and connect molecular composition to a functional membrane phenotype.

The Special Issue will span the diversity of membrane solutions across life. Contributions may address the archaeal–bacterial/eukaryotic lipid divide, ether- versus ester-linked membranes, glycerol-backbone chirality, heterochiral or mixed membranes, extremophile adaptation, and the evolution of membrane biosynthesis. Comparative studies of bacterial, archaeal, animal, plant, fungal, algal, and protist membranes are encouraged, provided that they identify general principles or lineage-specific advantages. Within eukaryotic cells, particular attention will be given to the distinct lipid identities of the plasma membrane, endoplasmic reticulum, Golgi apparatus, mitochondria, endosomes and lysosomes, peroxisomes, nuclear envelope, chloroplasts and thylakoids, lipid droplets, extracellular vesicles, and membrane contact sites.

A second priority is the reciprocal coupling between lipids and proteins. Studies may investigate specific lipid binding, hydrophobic matching, lateral-pressure profiles, electrostatic interactions, curvature stress, domain partitioning and the regulation of ion channels, receptors, transporters, enzymes, and cytoskeletal attachments. Membrane mechanics and electrodynamics, including phase transitions, ordered and disordered domains, ripple or non-lamellar states, bending, tension, thickness fluctuations, dipole potential, electromechanical coupling, and bioelectric signaling, are central to the scope of this Special Issue, provided that they are linked to molecular mechanisms and biological function.

The Special Issue also welcomes methodological and computational advances that make membrane state measurable and comparable: selective isolation and purity assessment of native membranes and organelles; targeted and untargeted LC–MS/MS lipidomics; phospholipidomics; ion mobility and mass-spectrometry imaging; single-cell, spatial, and subcellular lipidomics; Raman, infrared, and NMR spectroscopy; fluorescence-based order and asymmetry probes; AFM; scattering; cryo-electron microscopy; and rigorous quality-control and reporting standards. All-atom and coarse-grained molecular dynamics, continuum mechanics, multiscale models, machine learning, and predictive membrane-state atlases are encouraged, especially when predictions are validated experimentally.

Finally, the Special Issue will bridge native membranes and engineered systems. Suitable topics include liposomes, giant unilamellar vesicles, supported bilayers, nanodiscs, protocells, extracellular-vesicle mimetics, biomimetic nanoparticles, and lipid nanoparticles, provided that contributions yield mechanistic insights into composition–organization–function relationships. Translational contributions may examine membrane remodeling in infection, inflammation, cardiovascular and metabolic disorders, cancer, neurodegeneration, aging, pharmacology, toxicology, and anesthesia. Emerging proposals on membrane bioelectricity, electromagnetic responsiveness, or information processing are welcome when framed as testable molecular hypotheses with explicit controls and falsification criteria.

This Special Issue aims to:

• Establish composition → organization → physical state → function as a shared framework across membrane biology;
• Connect comparative and evolutionary membrane chemistry with organelle specialization and cellular regulation;
• Promote reproducible integration of lipidomics, membrane biophysics, functional assays, and computational modeling;
• Identify measurable membrane-state signatures relevant to physiology, disease, pharmacology, and bioengineering;
• Provide a rigorous platform for emerging membrane-centered hypotheses without conflating established mechanisms with exploratory claims.

In this Special Issue, original research articles, reviews, perspectives, and methodological papers are welcome. Research areas may include, but are not limited to, the following:

• Origins and evolution of cellular membranes: lipid divide, backbone chirality, ether/ester chemistry, mixed membranes, and minimal-cell models;
• Comparative membrane lipid biology in archaea, bacteria, animals, plants, fungi, algae, and protists;
• Plasma-membrane asymmetry, lipid domains, rafts, transbilayer movement, and membrane remodeling;
• Organelle-specific lipidomes, membrane contact sites, lipid trafficking, and inter-organelle communication;
• Mitochondrial, nuclear, endolysosomal, peroxisomal, chloroplast, and thylakoid membrane specialization;
• Lipid–protein interactions, hydrophobic mismatch, lateral pressure, curvature sensing, and regulation of membrane proteins;
• Membrane phase behavior, mechanics, permeability, electrostatics, dipole potential, and electromechanical coupling;
• Native-membrane isolation, phospholipidomics, single-cell/spatial/subcellular lipidomics, imaging, and analytical standardization;
• Molecular dynamics, continuum and multiscale modeling, machine learning, and predictive membrane-state atlases;
• Membrane remodeling in disease, infection, inflammation, aging, neurodegeneration, cancer, and cardiovascular or metabolic disorders;
• Pharmacological and toxicological perturbation of membranes, including anesthetics and membrane-active compounds;
• Synthetic and biomimetic membranes, nanodiscs, extracellular vesicles, protocells, and lipid nanoparticles.

Editorial emphasis
Priority will be given to submissions that integrate at least two levels of evidence—for example, a defined change in lipid composition together with a biophysical, structural, electrical, or functional readout. Purely descriptive lipid profiling without membrane localization, quality control, or mechanistic interpretation will not be the primary focus of this Special Issue.

I look forward to receiving your contributions.

Dr. Marco Cavaglià
Guest Editor

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