Membrane Lipid Dynamics Research Articles

Investigating the Influence of Photoswitchable Lipids on the Structure and Dynamics of Lipid Membranes: Fundamentals and Potential Applications.

In this work, we delve into the impact of photoisomerization of photoswitchable lipids (PSLs) on the membrane structure and dynamics at a molecular level. Through all-atom molecular dynamics simulations, we explore how UV irradiation-induced trans-to-cis isomerization of these lipids, particularly the azobenzene-derivatized phosphatidylcholine (AzoPC) lipid, influences the structure and dynamics of a simplified lipid membrane, mimicking those of E. coli bacteria across different temperatures. Our findings align with previous experimental observations regarding membrane properties and offer insights into localized effects and microscopic heterogeneity. Additionally, we estimate the relaxation time scale of the lipid membrane following AzoPC photoisomerization. Moreover, we demonstrate the feasibility of photoactivated drug release, exemplified by the controlled liberation of doxorubicin, an anticancer agent, through the membrane, suggesting the potential of PSLs in engineering photoactivated liposomes, coined as photoazosomes, for precise targeted drug delivery applications.

Cell-intrinsic mechanical regulation of plasma membrane accumulation at the cytokinetic furrow

Cytokinesis is the process where the mother cell's cytoplasm separates into daughter cells. This is driven by an actomyosin contractile ring that produces cortical contractility and drives cleavage furrow ingression, resulting in the formation of a thin intercellular bridge. While cytoskeletal reorganization during cytokinesis has been extensively studied, less is known about the spatiotemporal dynamics of the plasma membrane. Here, we image and model plasma membrane lipid and protein dynamics on the cell surface during leukemia cell cytokinesis. We reveal an extensive accumulation and folding of the plasma membrane at the cleavage furrow and the intercellular bridge, accompanied by a depletion and unfolding of the plasma membrane at the cell poles. These membrane dynamics are caused by two actomyosin-driven biophysical mechanisms: the radial constriction of the cleavage furrow causes local compression of the apparent cell surface area and accumulation of the plasma membrane at the furrow, while actomyosin cortical flows drag the plasma membrane toward the cell division plane as the furrow ingresses. The magnitude of these effects depends on the plasma membrane fluidity, cortex adhesion, and cortical contractility. Overall, our work reveals cell-intrinsic mechanical regulation of plasma membrane accumulation at the cleavage furrow that is likely to generate localized differences in membrane tension across the cytokinetic cell. This may locally alter endocytosis, exocytosis, and mechanotransduction, while also serving as a self-protecting mechanism against cytokinesis failures that arise from high membrane tension at the intercellular bridge.

Absence of alka(e)nes triggers profound remodeling of glycerolipid and carotenoid composition in cyanobacteria membrane.

Alka(e)nes are produced by many living organisms and exhibit diverse physiological roles, reflecting a high functional versatility. Alka(e)nes serve as waterproof wax in plants, communicating pheromones for insects, and microbial signaling molecules in some bacteria. Although alka(e)nes have been found in cyanobacteria and algal chloroplasts, their importance for photosynthetic membranes has remained elusive. In this study, we investigated the consequences of the absence of alka(e)nes on membrane lipid composition and photosynthesis using the cyanobacterium Synechocystis PCC6803 as a model organism. By following the dynamics of membrane lipids and the photosynthetic performance in strains defected and altered in alka(e)ne biosynthesis, we show that drastic changes in the glycerolipid contents occur in the absence of alka(e)nes, including a decrease in the membrane carotenoid content, a decrease in some digalactosyldiacylglycerol (DGDG) species and a parallel increase in monogalactosyldiacylglycerol (MGDG) species. These changes are associated with a higher susceptibility of photosynthesis and growth to high light in alka(e)ne-deficient strains. All these phenotypes are reversed by expressing an algal photoenzyme producing alka(e)nes from fatty acids. Therefore, alkenes, despite their low abundance, are an essential component of the lipid composition of membranes. The profound remodeling of lipid composition that results from their absence suggests that they play an important role in one or more membrane properties in cyanobacteria. Moreover, the lipid compensatory mechanism observed is not sufficient to restore normal functioning of the photosynthetic membranes, particularly under high-light intensity. We conclude that alka(e)nes play a crucial role in maintaining the lipid homeostasis of thylakoid membranes, thereby contributing to the proper functioning of photosynthesis, particularly under elevated light intensities.

UV-B Radiation Disrupts Membrane Lipid Organization and Suppresses Protein Mobility of GmNARK in Arabidopsis.

While it is well known that plants interpret UV-B as an environmental cue and a potential stressor influencing their growth and development, the specific effects of UV-B-induced oxidative stress on the dynamics of membrane lipids and proteins remain underexplored. Here, we demonstrate that UV-B exposure notably increases the formation of ordered lipid domains on the plasma membrane (PM) and significantly alters the behavior of the Glycine max nodule autoregulation receptor kinase (GmNARK) protein in Arabidopsis leaves. The GmNARK protein was located on the PM and accumulated as small particles in the cytoplasm. We found that UV-B irradiation interrupted the lateral diffusion of GmNARK proteins on the PM. Furthermore, UV-B light decreases the efficiency of surface molecule internalization by clathrin-mediated endocytosis (CME). In brief, UV-B irradiation increased the proportion of the ordered lipid phase and disrupted clathrin-dependent endocytosis; thus, the endocytic trafficking and lateral mobility of GmNARK protein on the plasma membrane are crucial for nodule formation tuning. Our results revealed a novel role of low-intensity UV-B stress in altering the organization of the plasma membrane and the dynamics of membrane-associated proteins.

Sum-frequency vibrational spectroscopy, a tutorial: Applications for the study of lipid membrane structure and dynamics.

Planar supported lipid bilayers (PSLBs) are an ideal model for the study of lipid membrane structures and dynamics when using sum-frequency vibrational spectroscopy (SFVS). In this paper, we describe the construction of asymmetric PSLBs and the basic SFVS theory needed to understand and make measurements on these membranes. Several examples are presented, including the determination of phospholipid orientation and measuring phospholipid transmembrane translocation (flip-flop).

Abstract 5574: Degradation of PIP4K2C by novel bivalent functional degrader LRK-A induces tumor regression in CRC

Abstract Phosphatidylinositol 5-phosphate 4-kinase, type II, gamma (PIP4K2C) is a lipid kinase with critical roles in vesicular trafficking, autophagy-dependent catabolism, and modulation of the immune system. Family members PIP4K2A and PIP4K2B are implicated in regulation of autophagy, cancer cell proliferation, and response to insulin, whereas PIP4K2C has a unique function in the immune response to cancer. Beyond the ability to convert PI5P to PI45P2, PIP4K2 kinases regulate membrane localization and clustering of PI45P2 and thus govern multiple aspects of membrane trafficking. These activities are likely to be independent of catalytic function1. The involvement of PIP4K2C in membrane lipid dynamics has the potential to broadly impact pro-tumor and immune-suppressive biology in cancer, including uptake of cancer cells by immune cells, and subsequently increase antigen processing, presentation, and T cell activation. Mice deficient in PIP4K2C develop immune cell infiltrates in tissues and increased proinflammatory cytokines in plasma2, suggesting that modulation of PIP4K2C could enhance anti-tumor immunity in cancer patients. Achieving potent targeting of PIP4K2C while sparing other family members or other lipid kinases has so far precluded the exploration of its potential as a therapeutic target. Here, we report the discovery of the highly potent and specific PIP4K2C bifunctional degrader LRK-A, which shows rapid and exclusive degradation of PIP4K2C. We show that LRK-A can rapidly and deeply degrade PIP4K2C in primary human PBMCs and cancer cells in vitro, and with broad species cross-reactivity. The specificity of LRK-A for PIP4K2C was established using whole-cell proteomic analyses, without co-degradation of off-target proteins including SALL4 and GSPT1. In mice treated with LRK-A, we observed a dose-dependent, profound, and sustained degradation of PIP4K2C. We further demonstrate that dosing of LRK-A as a single agent significantly reduced tumor growth, including full regressions, at low doses in a mouse syngeneic model of colorectal cancer. Collectively, our results show that PIP4K2C can be specifically and effectively targeted in vivo using a bifunctional degrader. The reduced tumor growth we observed upon targeting PIP4K2C alone suggests that PIP4K2C is a highly promising target for therapeutic intervention. Further explorations are ongoing to enable the development of PIP4K2C-targeted therapeutic strategies.

Covalent coupling of functionalized outer membrane vesicles (OMVs) to gold nanoparticles

Outer membrane vesicle-functionalized nanoparticles (OMV-NPs) have attracted significant interest, especially regarding drug delivery applications and vaccines. Here, we report on novel OMV-NPs by applying bioorthogonal click reaction for encapsulating gold nanoparticles (NPs) within outer membrane vesicles (OMVs) by covalent coupling. For this purpose, outer membrane protein A (OmpA), abundant in large numbers (due to 100,000 copies/cell [1]) in OMVs, was modified via the incorporation of the unnatural amino acid p–azidophenylalanine. The azide group was covalently coupled to alkyne-functionalized NPs after incorporation into OmpA. A simplified procedure using low-speed centrifugation (1,000 x g) was developed for preparing OMV-NPs. The OMV-NPs were characterized by zeta potential, Laurdan-based lipid membrane dynamics studies, and the enzymatic activity of functionalized OMVs with surface-displayed nicotinamide adenine dinucleotide oxidase (Nox). In addition, OMVs from attenuated bacteria (ClearColiTM BL21(DE3), E. coli F470) with surface-displayed Nox or antibody fragments were prepared and successfully coupled to AuNPs. Finally, OMV-NPs displaying single-chain variable fragments from a monoclonal antibody directed against epidermal growth factor receptor were applied to demonstrate the feasibility of OMV-NPs for tumor cell targeting.

Differences in Lipid Order and Dynamics in Plasma Membranes Assessed by Nonlinear Optical Microscopy.

When amphiphilic polar dyes were added to the cells, they intercalated predominantly in the outer leaf of the plasma membrane, making them active for second harmonic generation (SHG). The fluorescence of the dye enabled simultaneous 3D imaging of SHG and two-photon excited fluorescence (TPF). Because SHG intensity is sensitive to the alignment of the dyes, which reflects lipid ordering in the plasma membrane, we assessed the difference in lipid ordering by comparing the SHG intensity normalized to the TPF intensity. Together with an enzyme release assay that detects pore formation in the plasma membrane, our SHG assay revealed how polycations affect lipid ordering at low concentrations, where membrane damage has not yet been examined. By scaling the results of the assays with the charge concentration of the two polycations, polyethylenimine (PEI) and poly-l-lysine (PLL), we found that PEI reduced the lipid order more than PLL, and PLL formed more pores than PEI. A comparison of the SHG and TPF images of the wounded cells revealed that one of the lipid dynamics (flip-flop) was significantly enhanced in the bleb membrane. Moreover, the SHG assay indicated that the biocompatible polymer, poly(N-(2-hydroxypropyl)methacrylamide), did not affect the lipid order. Thus, our technique allows the assessment of the plasma membrane structure at the molecular level.

Decoding the role of mycobacterial lipid remodelling and membrane dynamics in antibiotic tolerance.

Current treatments for tuberculosis primarily target Mycobacterium tuberculosis (Mtb) infections, often neglecting the emerging issue of latent tuberculosis infection (LTBI) which are characterized by reduced susceptibility to antibiotics. The bacterium undergoes multiple adaptations during dormancy within host granulomas, leading to the development of antibiotic-tolerant strains. The mycobacterial membrane plays a crucial role in drug permeability, and this study aims to characterize membrane lipid deviations during dormancy through extensive lipidomic analysis of bacteria cultivated in distinct media and growth stages. The results revealed that specific lipids localize in different regions of the membrane envelope, allowing the bacterium to adapt to granuloma conditions. These lipid modifications were then correlated with the biophysical properties of the mycomembrane, which may affect interactions with antibiotics. Overall, our findings offer a deeper understanding of the bacterial adaptations during dormancy, highlighting the role of lipids in modulating membrane behaviour and drug permeability, ultimately providing the groundwork for the development of more effective treatments tailored to combat latent infections.

Curvature-enhanced membrane asymmetry slows down protein diffusion

Diffusion of transmembrane proteins plays a vital role in various cellular processes, such as endocytosis, raft formation and signal transduction. Current understanding of protein diffusion dynamics in lipid membranes is mostly based on hydrodynamic analyses, in which lipid membrane is simply treated as a thin layer of viscous liquid, same for highly curved ones. Therefore, how the mechanical state of highly curved membranes may affect the transmembrane protein diffusion remains unclear. In this study, we employed molecular dynamics (MD) simulations to analyse membrane curvature effect on the diffusion of cylindrically shaped Aquaporin-0 (AQP0) protein. Slowing down of protein diffusion with the increase in membrane curvature was observed. The possible contributions from membrane tension and asymmetric pressure profile were systematically investigated by simulating the protein diffusion dynamics in planar membranes with various tension levels or with various lipid number ratios between the two leaflets, respectively. We found no significant effect of membrane tension on AQP0 diffusion. Instead, the asymmetric pressure profile present in highly curved bilayer membranes was identified as a key factor that contributes to the slowing down of transmembrane protein diffusion. Our work thus contributes to a more complete picture of transmembrane protein diffusion on highly curved biological membranes.

Abstract 16909: Eicosapentaenoic Acid and Docosahexaenoic Acid Have Competing Effects on Membrane Lipid Dynamics Due to Differences in Structure

Background: Omega-3 fatty acids (n3-FAs) incorporate into vascular cell membranes where they modulate protein function and signal transduction. The n3-FA eicosapentaenoic acid (EPA) delivered in ethyl ester form (icosapent ethyl) reduced a broad range of cardiovascular events in high-risk patients (REDUCE-IT). This was not observed with mixed n3-FA formulations containing docosahexaenoic acid (DHA) in STRENGTH and other trials. These discordant outcomes indicate DHA may counter certain EPA effects due to its additional carbons and double bond. We compared these n3-FA effects on membrane lipid dynamics and width, key determinants of protein function. Methods: Membrane lipid fluidity was measured by fluorescence anisotropy approaches in large unilamellar vesicles (LUVs) of 100 nm diameter containing 1-palmitoyl-2-oleoyl-3-sn-phosphatidylcholine (POPC) and 50 mol% cholesterol with EPA and/or DHA (0-10 mol%). LUVs were treated with the fluorescent probe, 1,6-diphenyl-1,3,5-hexatriene (DPH), at 1 mol% and evaluated using a spectrofluorometer with a polarization accessory. Membrane width ( i.e ., unit cell periodicity) of the samples was determined by small angle x-ray scattering (SAXS). Results: DHA alone increased bulk lipid fluidity as indicated by a dose-dependent reduction in apparent rotational correlation time (ARCT); at 10 mol%, there was a ~20% (p<0.05) reduction from ~19 to ~16 nsec compared to control (untreated membranes). By contrast, EPA had no significant disordering effect except when combined at equimolar levels; the EPA/DHA combination showed a reduction in ARCT to ~18 nsec at 10 mol% that was different from EPA alone (p<0.05). Consistent with these findings, SAXS analysis showed DHA containing membranes had a reduced width compared to EPA by 5% or 3 Å (p<0.05) due to increased trans-gauche isomerizations in the phospholipid acyl chains. Conclusion: EPA maintained membrane fluidity while DHA increased fluidity and thereby reduced membrane width due to its additional carbons and double bond. The EPA/DHA combination increased membrane fluidity compared to control and EPA alone. The disordering effects of DHA may counter EPA stabilizing effects and explain discordant clinical outcomes with different n3-FA formulations.

Effect of Host Cholesterol on the Membrane Dynamics of Outer Membrane Lipids of Mycobacteria.

The ability of Mycobacterium tuberculosis to remain dormant after primary infection represents the prime cause of new TB cases throughout the world. Hence, diagnosis and treatment of individuals hosting dormant mycobacterium is one of the crucial strategies to be adopted for the prevention of Tuberculosis. Among many strategies unleashed by the latent bacterium, one of them is scavenging host cholesterol for carbon source. Cholesterol modifies lipid membranes over many scales and here, its effect on mycobacterial membrane biophysics and the subsequent effect on partitioning of antibiotics into cholesterol- enriched mycobacterial membranes was investigated. Our research showed that cholesterol alters the phase state behavior of mycobacterial outer membrane lipids by enhancing the overall membrane order at the headgroup and acyl chain region and is integrated into both ordered and disordered domains/phases, with a preference for the latter. Exogenous cholesterol further alters the drug partitioning behavior of structurally different drugs, pointing to a larger clinical potential of using more hydrophobic medications to target dormant bacteria.

Quantitative image mean squared displacement (iMSD) analysis of the dynamics of Aquaporin 2 within the membrane of live cells

Nanodomains are a biological membrane phenomenon which have a large impact on various cellular processes. They are often analysed by looking at the lateral dynamics of membrane lipids or proteins. The localization of the plasma membrane protein aquaporin-2 in nanodomains has so far been unknown. In this study, we use total internal reflection fluorescence microscopy to image Madin-Darby Canine Kidney (MDCK) cells expressing aquaporin-2 tagged with mEos 3.2. Then, image mean squared displacement (iMSD) approach was used to analyse the diffusion of aquaporin-2, revealing that aquaporin-2 is confined within membrane nanodomains. Using iMSD analysis, we found that the addition of the drug forskolin increases the diffusion of aquaporin-2 within the confined domains, which is in line with previous studies. Finally, we observed an increase in the size of the membrane domains and the extent of trapping of aquaporin-2 after stimulation with forskolin.

Unique amphipathic α helix drives membrane insertion and enzymatic activity of ATG3.

Autophagosome biogenesis requires a localized perturbation of lipid membrane dynamics and a unique protein-lipid conjugate. Autophagy-related (ATG) proteins catalyze this biogenesis on cellular membranes, but the underlying molecular mechanism remains unclear. Focusing on the final step of the protein-lipid conjugation reaction, the ATG8/LC3 lipidation, we show how the membrane association of the conjugation machinery is organized and fine-tuned at the atomistic level. Amphipathic α helices in ATG3 proteins (AHATG3) have low hydrophobicity and contain less bulky residues. Molecular dynamics simulations reveal that AHATG3 regulates the dynamics and accessibility of the thioester bond of the ATG3~LC3 conjugate to lipids, enabling the covalent lipidation of LC3. Live-cell imaging shows that the transient membrane association of ATG3 with autophagic membranes is governed by the less bulky-hydrophobic feature of AHATG3. The unique properties of AHATG3 facilitate protein-lipid bilayer association, leading to the remodeling of the lipid bilayer required for the formation of autophagosomes.

Neutron scattering studies on dynamics of lipid membranes.

Neutron scattering methods are powerful tools for the study of the structure and dynamics of lipid bilayers in length scales from sub Å to tens to hundreds nm and the time scales from sub ps to μs. These techniques also are nondestructive and, perhaps most importantly, require no additives to label samples. Because the neutron scattering intensities are very different for hydrogen- and deuterium-containing molecules, one can replace the hydrogen atoms in a molecule with deuterium to prepare on demand neutron scattering contrast without significantly altering the physical properties of the samples. Moreover, recent advances in neutron scattering techniques, membrane dynamics theories, analysis tools, and sample preparation technologies allow researchers to study various aspects of lipid bilayer dynamics. In this review, we focus on the dynamics of individual lipids and collective membrane dynamics as well as the dynamics of hydration water.

A Systematic Review of Piperine as a Bioavailability Enhancer

Drug oral absorption is a crucial concern, particularly when the medication is costly, poorly bioavailable, and administered for extended periods of time. Chemical substances known as "bioenhancers" are those that, when combined with pharmaceuticals, increase their bioavailability without having a synergistic impact on the drug itself. Toxicity, expense, poor bioavailability, and long-term medication administration all contribute to the need for bioenhancers, which aid in solving the majority of these issues. Piperine, also known as 1-peperoyl piperidine, is an aromatic alkaloid produced by the Piper species. Piperine alters the lipid milieu and membrane dynamics at the site of absorption to improve permeability. The molecular nature of piperine makes it appropriate for inhibiting enzymes. By blocking several metabolising enzymes, it increases the bioavailability of many medications, including carbamazepine, curcumin, ciprofloxacin, ampicillin, metronidazole, oxytetracycline, and many more. As a result, piperine, a potent inhibitor of medication metabolism, effectively increases absorption. The mechanism, metabolic inhibition, influence of structural alterations on activity, and medications that are bioenhanced by piperine are all explored in the review that follows. It offers insight into the use of piperine as a useful bioenhancer and the advantages of a bioenhanced drug formulation over one without one. Bioavailability enhancers are typically plant-based molecules that support the biological activity, bioavailability, or uptake of drugs in combination therapy. This review article finishes with discussing piperine's capacity to increase bioavailability.
 Keywords: Bioenhancers, Piperine, Oral absorption, Alkaloid.

Effects of Shape on Interaction Dynamics of Tetrahedral Nanoplastics and the Cell Membrane.

Cellular uptake of nanoplastics is instrumental in their environmental accumulation and transfer to humans through the food chain. Despite extensive studies using spherical plastic nanoparticles, the influence of the morphological characteristics of environmentally released nanoplastics is understudied. Using dissipative particle dynamics simulations, we modeled the interactions between a cell membrane and hydrophobic nanotetrahedra, which feature high shape anisotropy and large surface curvature seen for environmental nanoplastics. We observe robust uptake of nanotetrahedra with sharp vertices and edges by the lipid membrane. Two local energy minimum configurations of nanotetrahedra embedded in the membrane bilayer were identified for particles of large sizes. Further analysis of particle dynamics within the membrane shows that the two interaction states exhibit distinct translational and rotational dynamics in the directions normal and parallel to the plane of the membrane. The membrane confinement significantly arrests the out-of-plane motion, resulting in caged translation and subdiffusive rotation. While the in-plane diffusion remains Brownian, we find that the translational and rotational modes decouple from each other as the particle size increases. The rotational diffusion decreases by a greater extent compared to the translational diffusion, deviating from the continuum theory predictions. These results provide fundamental insights into the shape effect on the nanoparticle dynamics in crowded lipid membranes.

The electromechanics of lipid membranes: A dimensionally-reduced theory.

Lipid membranes separate the interior and exterior of a biological cell and its organelles. Their viscous-elastic material behavior gives rise to intriguing lipid membrane dynamics. However, lipid membrane dynamics are also affected by the presence of an electric field. For instance, lipid vesicles deform into prolates, oblates, and other shapes and even form pores when an electric field is applied. Furthermore, varying ionic concentrations across the boundary and within the interior of cells and organelles expose lipid membranes to electric fields in physiological conditions. Thus, understanding the electromechanics of lipid membranes is essential for many biological and experimental processes, such as the propagation of action potentials and the electroformation of lipid vesicles. Studying the electromechanics of lipid membranes on long lengths- and timescales requires a continuum physics framework. While continuum models are well-established for the pure mechanics of lipid membranes, a continuum model that captures the coupling between mechanical deformations and electric fields is currently missing. Capturing the effects of electric fields requires resolving the electric potential through the thickness of the lipid membrane. Current continuum approaches, however, treat lipid membranes as two-dimensional manifolds, making them unsuitable for describing the electromechanics of lipid membranes. Thus, we propose a new dimension reduction procedure for differential equations on thin bodies. Using this approach, we derive new surface theories for the electrostatics and mechanics of lipid membranes. Combining them, we obtain a novel continuum model for the electromechanics of lipid membranes. After discussing the new model, we apply it to a fluctuating lipid membrane in an external electric field and demonstrate the effect of accounting for the finite thickness of lipid membranes.

Domain-induced dynamics in phase-separating lipid membranes.

Lipid membranes have a significant role in cells, not only defining the boundaries of cells and cell organelles but also playing an active role in cell functions, including the partitioning of proteins and the spatiotemporal regulation of signaling clusters. This is facilitated by the rich lipid diversity in cell membranes, which often results in unideal mixing and subsequent lipid phase-separation into lateral compositional heterogeneities or domains. Over the past few decades, structural measurements on such membranes have shed important light on the molecular mechanisms underlying domain formation. However, major information gaps still exist in our understanding of how domain formation affects the dynamics of lipid membranes, whether in the form of collective fluctuations or molecular motions. To address this outstanding question, we use neutron spectroscopy and molecular dynamics (MD) simulations that can selectively investigate the matrix dynamics in domain-forming membranes. Specifically, our studies are performed on binary mixtures of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and deuterated 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). Experimental results, obtained by neutron spin-echo spectroscopy and neutron backscattering spectroscopy, show that the formation and growth of rigid DSPC domains causes an effective slowdown in the bending fluctuations and diffusional dynamics of the otherwise fluid DMPC matrix. MD simulations on cognate bilayers suggest that the measured changes in the matrix dynamics are mediated by interfacial DMPC lipids that experience constrained diffusional jumps and longer residence times at the domain boundaries. Our findings present striking evidence of dynamic coupling between lipid domains and their surrounding lipid environment. More importantly, this interplay occurs on the nanosecond time scales of protein conformational changes and signaling events. Put together, the results suggest an intriguing mechanism by which domain formation can play a regulatory role in functional membrane processes.

Analyzing membrane mechanics and lipid dynamics using lateral lipid density fluctuations.

The lateral lipid distribution describes the density of different lipid species in the membrane and reveals structural information about the membrane composition. The diffusion of lipids throughout the membrane is an essential part of many biological processes, specifically, they can redistribute along the membrane due to curvature. This redistribution process leads to a softening of the membrane. By analyzing fluctuations in the lateral density, we can reveal the important physics associated with the redistribution process.