Curvature-Induced Spatial Ordering of Composition in Lipid Membranes.
Ontology highlight
ABSTRACT:
SUBMITTER: Katz S
PROVIDER: S-EPMC5394915 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Laurdan fluorescence, novel spectral fitting, and dynamic light scattering were combined to determine lateral lipid organization in mixed lipid membranes of the oxidized lipid, 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine (PGPC), and each of the three bilayer lipids, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and 1-palmitoyl-2-oleoylphosphatidylcholine (POPC). Second harmonic spectra were computed to determine the number of elementary emissions present. All mixtures indicated two emissions. Accordingly, spectra were fit to two log-normal distributions. Changes with PGPC mole fraction, XPGPC, of the area of the shorter wavelength line and of dynamic light scattering-derived aggregate sizes show that: DPPC and PGPC form component-separated mixed vesicles for XPGPC ≤ 0.2 and coexisting vesicles and micelles for XPGPC > 0.2 in gel and liquid-ordered phases and for all XPGPC in the liquid-disordered phase; POPC and PGPC form randomly mixed vesicles for XPGPC ≤ 0.2 and component-separated mixed vesicles for XPGPC > 0.2. DOPC and PGPC separate into vesicles and micelles. Component segregation is due to unstable inhomogeneous membrane curvature stemming from lipid-specific intrinsic curvature differences between mixing molecules. PGPC is inverse cone-shaped because its truncated tail with a terminal polar group points into the interface. It is similar to and mixes with POPC, also an inverse cone because of mobility of its unsaturated tail. PGPC is least similar to DOPC because mobilities of both unsaturated tails confer a cone shape to DOPC, and PGPC separates form DOPC. DPPC and PGPC do not mix in the liquid-disordered phase because mobility of both tails in this phase renders DPPC a cone. DPPC is a cylinder in the gel phase and of moderate similarity to PGPC and mixes moderately with PGPC.
| S-EPMC7175694 | biostudies-literature
Project description:The Gaussian curvature modulus ?¯ of lipid bilayers likely contributes more than 100 kcal/mol to every cellular fission or fusion event. This huge impact on membrane remodeling energetics might be a factor that codetermines the complex lipid composition of biomembranes through tuning of ?¯. Yet, its value has been measured only for a handful of simple lipids, and no simulation has so far determined it better than a factor of two, rendering a systematic investigation of such enticing speculations impossible. Here we propose a highly accurate method to determine ?¯ in computer simulations. It relies on the interplay between curvature stress and edge tension of partially curved axisymmetric membrane disks and requires determining their closing probability. For a simplified lipid model we obtain ?¯ and its relation to the normal bending modulus ? for membranes differing both in stiffness and spontaneous lipid curvature. The elastic ratio ?¯/? can be determined with a few percent statistical accuracy. Its value agrees with the scarce experimental data, and its change with spontaneous lipid curvature is compatible with theoretical expectations, thereby granting additional information on monolayer properties. We also show that an alternative determination of these elastic parameters based on moments of the lateral stress profile gives markedly different and unphysical values.
| S-EPMC3309410 | biostudies-literature
Project description:Lipid and protein sorting and trafficking in intracellular pathways maintain cellular function and contribute to organelle homeostasis. Biophysical aspects of membrane shape coupled to sorting have recently received increasing attention. Here we determine membrane tube bending stiffness through measurements of tube radii, and demonstrate that the stiffness of ternary lipid mixtures depends on membrane curvature for a large range of lipid compositions. This observation indicates amplification by curvature of cooperative lipid demixing. We show that curvature-induced demixing increases upon approaching the critical region of a ternary lipid mixture, with qualitative differences along two roughly orthogonal compositional trajectories. Adapting a thermodynamic theory earlier developed by M. Kozlov, we derive an expression that shows the renormalized bending stiffness of an amphiphile mixture membrane tube in contact with a flat reservoir to be a quadratic function of curvature. In this analytical model, the degree of sorting is determined by the ratio of two thermodynamic derivatives. These derivatives are individually interpreted as a driving force and a resistance to curvature sorting. We experimentally show this ratio to vary with composition, and compare the model to sorting by spontaneous curvature. Our results are likely to be relevant to the molecular sorting of membrane components in vivo.
| S-EPMC2749792 | biostudies-literature
Project description:Objects floating at a liquid interface, such as breakfast cereals floating in a bowl of milk or bubbles at the surface of a soft drink, clump together as a result of capillary attraction. This attraction arises from deformation of the liquid interface due to gravitational forces; these deformations cause excess surface area that can be reduced if the particles move closer together. For micrometer-sized colloids, however, the gravitational force is too small to produce significant interfacial deformations, so capillary forces between spherical colloids at a flat interface are negligible. Here, we show that this is different when the confining liquid interface has a finite curvature that is also anisotropic. In that case, the condition of constant contact angle along the three-phase contact line can only be satisfied when the interface is deformed. We present experiments and numerical calculations that demonstrate how this leads to quadrupolar capillary interactions between the particles, giving rise to organization into regular square lattices. We demonstrate that the strength of the governing anisotropic interactions can be rescaled with the deviatoric curvature alone, irrespective of the exact shape of the liquid interface. Our results suggest that anisotropic interactions can easily be induced between isotropic colloids through tailoring of the interfacial curvature.
| S-EPMC3677486 | biostudies-literature
Project description:In various biological processes such as endocytosis and caveolae formation, the cell membrane is locally deformed into curved morphologies. Previous models to study membrane morphologies resulting from locally induced curvature often only consider the possibility of axisymmetric shapes-an indeed unphysical constraint. Past studies predict that the cell membrane buds at low resting tensions and stalls at a flat pit at high resting tensions. In this work, we lift the restriction to axisymmetry to study all possible membrane morphologies. Only if the resting tension of the membrane is low, we reproduce axisymmetric membrane morphologies. When the resting tension is moderate to high, we show that 1) axisymmetric membrane pits are unstable and 2) nonaxisymmetric ridge-shaped structures are energetically favorable. Furthermore, we find the interplay between intramembrane viscous flow and the rate of induced curvature affects the membrane's ability to transition into nonaxisymmetric ridges and axisymmetric buds. In particular, we show that axisymmetric buds are favored when the induced curvature is rapidly increased, whereas nonaxisymmetric ridges are favored when the curvature is slowly increased. Our results hold relevant implications for biological processes such as endocytosis and physical phenomena like phase separation in lipid bilayers.
| S-EPMC7499066 | biostudies-literature
Project description:We show by molecular dynamics that amphiphilic Au nanoparticles (NP) with a diameter of 4 nm generate curvature in phosphatidylcholine lipid membranes. NPs generate negative curvature when they adsorb on the membrane surface but, as they get spontaneously and progressively embedded into the membrane core, the curvature turns positive. As membrane embedding is kinetically slow, both configurations can be observed by Cryo-EM. NP-induced curvature explains the peculiar structure of liposome-liposome interfaces in presence of NPs.
| S-EPMC8530203 | biostudies-literature
Project description:Parkinson's disease is characterized by the presence of intracellular aggregates composed primarily of the neuronal protein ?-synuclein (?S). Interactions between ?S and various cellular membranes are thought to be important to its native function as well as relevant to its role in disease. We use fluorescence correlation spectroscopy to investigate binding of ?S to lipid vesicles as a function of the lipid composition and membrane curvature. We determine how these parameters affect the molar partition coefficient of ?S, providing a quantitative measure of the binding energy, and calculate the number of lipids required to bind a single protein. Specific anionic lipids have a large effect on the free energy of binding. Lipid chain saturation influences the binding interaction to a lesser extent, with larger partition coefficients measured for gel-phase vesicles than for fluid-phase vesicles, even in the absence of anionic lipid components. Although we observe variability in the binding of the mutant proteins, differences in the free energies of partitioning are less dramatic than with varied lipid compositions. Vesicle curvature has a strong effect on the binding affinity, with a >15-fold increase in affinity for small unilamellar vesicles over large unilamellar vesicles, suggesting that ?S may be a curvature-sensing protein. Our findings provide insight into how physical properties of the membrane may modulate interactions of ?S with cellular membranes.
| S-EPMC3042580 | biostudies-literature
Project description:Although membrane environment is known to boost drug metabolism by mammalian cytochrome?P450s, the factors that stabilize the structural folding and enhance protein function are unclear. In this study, we use peptide-based lipid nanodiscs to "trap" the lipid boundaries of microsomal cytochrome?P450 2B4. We report the first evidence that CYP2B4 is able to induce the formation of raft domains in a biomimetic compound of the endoplasmic reticulum. NMR experiments were used to identify and quantitatively determine the lipids present in nanodiscs. A combination of biophysical experiments and molecular dynamics simulations revealed a sphingomyelin binding region in CYP2B4. The protein-induced lipid raft formation increased the thermal stability of P450 and dramatically altered ligand binding kinetics of the hydrophilic ligand BHT. These results unveil membrane/protein dynamics that contribute to the delicate mechanism of redox catalysis in lipid membrane.
| S-EPMC6289274 | biostudies-literature
Project description:Proteins anchored to membranes through covalently linked fatty acids and/or isoprenoid groups play crucial roles in all forms of life. Sorting and trafficking of lipidated proteins has traditionally been discussed in the context of partitioning to membrane domains of different lipid composition. We recently showed that membrane shape/curvature can in itself mediate the recruitment of lipidated proteins. However, exactly how membrane curvature and composition synergize remains largely unexplored. Here we investigated how three critical structural parameters of lipids, namely acyl chain saturation, headgroup size, and acyl chain length, modulate the capacity of membrane curvature to recruit lipidated proteins. As a model system we used the lipidated minimal membrane anchor of the GTPase, N-Ras (tN-Ras). Our data revealed complex synergistic effects, whereby tN-Ras binding was higher on planar DOPC than POPC membranes, but inversely higher on curved POPC than DOPC membranes. This variation in the binding to both planar and curved membranes leads to a net increase in the recruitment by membrane curvature of tN-Ras when reducing the acyl chain saturation state. Additionally, we found increased recruitment by membrane curvature of tN-Ras when substituting PC for PE, and when decreasing acyl chain length from 14 to 12 carbons (DMPC versus DLPC). However, these variations in recruitment ability had different origins, with the headgroup size primarily influencing tN-Ras binding to planar membranes whereas the change in acyl chain length primarily affected binding to curved membranes. Molecular field theory calculations recapitulated these findings and revealed lateral pressure as an underlying biophysical mechanism dictating how curvature and composition synergize to modulate recruitment of lipidated proteins. Our findings suggest that the different compositions of cellular compartments could modulate the potency of membrane curvature to recruit lipidated proteins and thereby synergistically regulate the trafficking and sorting of lipidated proteins.
| S-EPMC5607143 | biostudies-literature
Project description:Epsins belong to the family of highly conserved clathrin-associated sorting proteins that are indispensable for clathrin-mediated endocytosis, but their precise functions remain unclear. We have developed an assay system of budded supported membrane tubes displaying planar and highly curved membrane surfaces to analyze intrinsic membrane curvature preference shown by clathrin-associated sorting proteins. Using real-time fluorescence microscopy, we find that epsin preferentially partitions to and assembles clathrin on highly curved membrane surfaces. Sorting of epsin to regions of high curvature strictly depends on binding to phosphatidylinositol 4,5-bisphosphate. Fluorescently labeled clathrins rapidly assemble as foci, which in turn cluster epsin, while maintaining tube integrity. Clathrin foci grow in intensity with a typical time constant of ?75 s, similar to the time scales for coated pit formation seen in cells. Epsin therefore effectively senses membrane curvature to spatially control clathrin assembly. Our results highlight the potential role of membrane curvature in orchestrating the myriad molecular interactions necessary for the success of clathrin-mediated membrane budding.
| S-EPMC4505496 | biostudies-literature