Open research questions in Lipid Membrane Structure and Behavior
154 unresolved questions extracted from the limitations and future-work sections of 453 Lipid Membrane Structure and Behavior papers in our library. Each links back to the study that raised it.
What the literature leaves open
The dynamic regulation of biomolecular condensates remains unclear. A systematic frequency-domain analysis of concentration buffering by condensates is lacking. The quantitative connection between LLPS parameters and the disturbance rejection properties of biomolecular condensates is not well understood.
The complexity of the lipidome of minimal cells. The need to balance membrane stability and permeability. The challenge of scaling up molecular dynamics simulations to the whole-cell scale.
The physicochemical design, structure and permeability of the JCVI-syn3A minimal cell membrane · 2026 · DOIThe lipidome of minimal cells remains largely unexplored. The physicochemical principles underlying minimal cell membranes are not well understood. There is a need to investigate how lipid composition enables passive permeation while maintaining membrane integrity.
The physicochemical design, structure and permeability of the JCVI-syn3A minimal cell membrane · 2026 · DOIThe limitations of current drug delivery systems in providing sustained release over extended periods. The challenge of controlling the initial rapid ('burst') release that occurs immediately after administration of a delivery system. The need for a simple and efficient platform for local delivery of hydrophilic drugs.
Ultra-slow release of hydrophilic drugs via multilamellar–multivesicular liposomes formed by unsaturated phospholipids · 2026 · DOI, a localized internal source assists release of the smaller particle yet is insufficient to systematically free the larger one, while activity distributed across the whole nanoparticle drives complete release even in the larger case.
Physical mechanisms of nanoparticle intracellular release through membrane pore nucleation and expansion · 2026 · DOIWhile the initial steps have been intensively studied, the intracellular release of a nanocarrier has received comparatively less attention and remains poorly understood.
Physical mechanisms of nanoparticle intracellular release through membrane pore nucleation and expansion · 2026 · DOIThe molecular basis of this physical state and its relationship with envelope mechanics remain unclear.
Severe acute respiratory syndrome coronavirus (SARS-CoV) assembles and buds from the Golgi apparatus or the ER membrane, but the specific membrane microdomains utilized during this process remain underexplored.
Selective Budding of SARS-CoV-Like Particles from Glycolipid-Enriched Membrane Lipid Rafts and Host Gene Modulation · 2026 · DOIHowever, the precise regulatory mechanism of cholesterol in SARS-CoV-2 fusion remains unknown.
Despite its significance in biology and materials science, the dynamics of multicomponent vesicles under shear flow remains poorly understood because of its nonlinear and strongly coupled nature, especially regarding the role of membrane heterogeneity in driving non-equilibrium behaviour.
Lipid nanoparticles have emerged as critical platforms for bioactive agent delivery, with their success in COVID-19 vaccines highlighting the urgent need to address gaps in understanding their biological interactions.
The Internal Nanostructure of Lipid Nanoparticles Influences Their Diverse Cellular Uptake Pathways · 2025 · DOIHow these changes in PM lipid organization regulate membrane properties and affect bleb formation remains unknown.
Loss of lipid asymmetry facilitates plasma membrane blebbing by decreasing membrane lipid packing · 2025 · DOIThe mechanisms by which fusion proteins utilize specific host lipids to drive virus-host membrane fusion remains elusive.
Viral fusion proteins of classes II and III recognize and reorganize complex biological membranes · 2025 · DOIWith conflicting reports on the association between cholesterol and CD8 T cell function, clarifying the relationship between membrane biophysical properties and T cell state offers an innovative perspective.
Validation of a fluorescence spectroscopy method for the determination of T cell membrane order, towards a high-throughput approach 2612 · 2025 · DOIThe effects and mechanisms of polyunsaturated fatty acids (PUFAs) including docosahexaenoic acid (DHA) and arachidonic acid (ARA) contained in the lipid membrane of neurons in the production of amyloid β (Aβ), a pathogenic molecule in Alzheimer's disease (AD), remain unclear.
Polyunsaturated fatty acids in lipid membranes regulate human neuronal function and amyloid-β production · 2025 · DOITo date, however, the ALA gene family and its expression patterns under abiotic and biotic stresses have not been studied in the soybean genome.
Genome-wide identification of the P4ATPase gene family and its response to biotic and abiotic stress in soybean (Glycine max L.) · 2025 · DOIDespite evidence of chiral preferences in biological responses, the molecular origin of chiral selectivity remains unclear.
Decoding Chiral Interactions: Molecular Insights into the Selective Binding of Nanoparticles at Biological Interfaces · 2025 · DOIThe folded, solvent-exposed unfolded, and membrane-inserted states of pHLIP have been well-characterized, but the intermediate structures remain poorly understood.
Membrane Interactions Drive Hydrogen-Bond Dynamics in the pH-Low Insertion Peptide (pHLIP) · 2025 · DOIStudies have focused on understanding folding and membrane interactions; however, there is a relation between the environment, membrane interactions, and local picosecond dynamics that has not been characterized.
Membrane Interactions Drive Hydrogen-Bond Dynamics in the pH-Low Insertion Peptide (pHLIP) · 2025 · DOIWhile the effects of vertical electric fields ( E Vert ) across the membranes have been extensively studied, the influence of horizontal (in-plane) electric fields ( E Horz ) remains poorly understood.
Distinct Structural Responses of Lipid Bilayers to Horizontal and Vertical Electric Fields · 2025 · DOIWhile evidence shows that lipid scrambling can occur via an open hydrophilic pathway (groove) that spans the membrane, it remains unclear if all family members facilitate lipid movement in this manner.
Simulation-based survey of TMEM16 family reveals that robust lipid scrambling requires an open groove · 2025 · DOIThis site is coupled to key regions in the protein, but the impact of glycans on these allosteric effects has not been investigated.
Whether and how lipid peroxidation impacts the lateral organization of proteins and lipids in biological membranes, however, remains poorly understood.
Lipid Peroxidation Drives Liquid–Liquid Phase Separation and Disrupts Raft Protein Partitioning in Biological Membranes · 2024 · DOIWhile many studies regarding protein adsorption on the surface of liposomes with different compositions have been performed, to the best of our knowledge, the differential responses of CHOL and DOTAP upon albumin adsorption on vesicles have not yet been investigated.
Ergosterol, found in fungi and some protist membranes, is understudied compared with cholesterol from animal membranes.
Most-cited papers in Lipid Membrane Structure and Behavior
- Functional rafts in cell membranes · Nature · 1997 · 8,402 citations
- The Fluid Mosaic Model of the Structure of Cell Membranes · Science · 1972 · 7,197 citations
- Liquid phase condensation in cell physiology and disease · Science · 2017 · 4,298 citations
- Lipid Rafts As a Membrane-Organizing Principle · Science · 2009 · 3,991 citations
- Models for the Specific Adhesion of Cells to Cells · Science · 1978 · 3,981 citations
- Polymer Vesicles · Science · 2002 · 3,501 citations
- Pore-forming activity and structural autoinhibition of the gasdermin family · Nature · 2016 · 2,525 citations
- Phosphoinositides in cell regulation and membrane dynamics · Nature · 2006 · 2,432 citations
- Polymersomes: Tough Vesicles Made from Diblock Copolymers · Science · 1999 · 2,345 citations
- THE BARRIER FUNCTION OF THE GRAM‐NEGATIVE ENVELOPE · Annals of the New York Academy of Sciences · 1974 · 441 citations
Most recent work
- Nanometer condensate organization in live cells derived from partitioning measurements · bioRxiv · 2026
- Atg1 phosphorylates Atg2 to gate phospholipid flow through a continuous conduit for autophagosome biogenesis · bioRxiv · 2026
- Exogenous sphingomyelinase mediates MSC-derived EV biogenesis and enhances potency via repackaging of molecular cargo · iScience · 2026
- Selective Budding of SARS-CoV-Like Particles from Glycolipid-Enriched Membrane Lipid Rafts and Host Gene Modulation · Microorganisms · 2026
- CHARMM-GUI Quick Bilayer: Simple and Intuitive One-Stop Membrane Bilayer Builder · Journal of Molecular Biology · 2026
- Disorder in Order-Related Membrane Biophysical Parameters: An In-Depth Analysis of Di-4-ANEPPDHQ Generalized Polarization · The Journal of Physical Chemistry Letters · 2026
- FERONIA orchestrates plasma membrane nanoclusters for plant thermotolerance · Science · 2026
- Dynamic principles of concentration buffering through liquid–liquid phase separation · Proceedings of the National Academy of Sciences · 2026
- On the effect of applied lateral tension on the deformation energetics of biological membranes and the lipid dynamics within · bioRxiv · 2026
- Microfluidic preparation of size- and lamellarity-controlled liposomes using a static mixer and the advantage of a multilamellar structure in biosensing applications · Frontiers in Bioengineering and Biotechnology · 2026
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