Lateral Diffusion Coefficient Research Articles

Correlated Lateral Diffusion of Lipids

Recent years have witnessed a proliferation of publications concerning the lateral diffusion of membrane lipids. The reported diffusion coefficient (D) values appear to depend on systems under study and on techniques of investigation. There is no clear consensus regarding their dynamics that would explain the different D values as well as the relation between mobility and the radius of the diffusing object.Here we focus on the lateral diffusion of lipids, which has been less scrutinized than that of membrane proteins. Using fluorescence recovery after photobleaching, we have obtained lateral diffusion coefficients of lipids inserted into bilayers of giant unilamellar vesicles. We demonstrate that lipids diffuse with various diffusion coefficients ranging from D = 3.7 ± 0.4 to 13.9 ± 0.6 μm2/s, and that these values depend on the type of lipid. Interestingly, a transmembrane peptide, having nearly the same radius as lipids and whose hydrophobic thickness matches that of the bilayer, exhibits a D value of 9.6 ± 0.4 μm2/s. Since the lipids and the transmembrane peptide possess a similar diameter and lipids do not span membranes, the peptide diffusion coefficient is expected to be smaller than that of lipids, which is obviously not the case. Our systematic study suggests that the slower diffusion of lipids (as compared to that of the transmembrane peptide) is caused by the formation of dynamic lipid nano-patches that diffuse like a single object with an increased radius. These nano-patches seem to form more spontaneously when lipids are saturated. Consequently, one should be cautious when comparing diffusion coefficient of transmembrane proteins and lipids. Transmembrane peptides should be used as a reference instead of lipids.

Lateral Diffusion of Dispersing Molecules on Nanotubes As Probed by NMR

Noncovalent dispersion of carbon nanotubes is essential to most applications but still poorly understood at the molecular level. The interaction of the dispersing molecule with the nanotube, wrapping or nonwrapping, still awaits consensus. Herein, we have studied by 1H NMR diffusometry some features of molecular dynamics in the system of carbon nanotubes dispersed by triblock copolymer Pluronics F127 in water. The diffusional decays obtained at different diffusion times, Δ, are not single-exponential and have a complex Δ-dependent profile, ultimately implying that the polymer is observed in two states: free (in unimeric form) and nanotube-bound. Fitting a two-site exchange model to the data indicates that at any instant, only a small fraction of polymers are adsorbed on the nanotubes, with polydisperse residence times in the range of 100–400 ms. Most significantly, we further provide an estimate of D = (3–8) × 10–12 m2 s–1 for the coefficient of lateral diffusion of the polymer along the nanotube surface, which is an order of magnitude slower than the corresponding self-diffusion coefficient in water. The emerging picture is that of a nonwrapping mode for the polymer–nanotube interaction.

Dynamics and stability of lipid bilayers modulated by thermosensitive polypeptides, cholesterols, and PEGylated lipids

Lipid bilayers, which consist of dipalmitoylglycerophosphocholines (DPPCs), PEGylated lipids, cholesterols, and elastin-like polypeptides (ELPs; [VPGVG]3) at different molar ratios, were simulated. Simulations were carried out for 2 μs using the coarse-grained (CG) model that had captured the experimentally observed phase behavior of PEGylated lipids and lateral diffusivity of DPPC bilayers. Starting with the initial position of ELPs on the bilayer surface, ELPs insert into the hydrophobic region of the bilayer because of their interaction with lipid tails, consistent with previous all-atom simulations. Lateral diffusion coefficients of DPPCs significantly increase in the bilayer composed of more ELPs and less cholesterols, showing their opposite effects on the bilayer dynamics. In particular, ELPs modulate the dynamics and phase for the disordered liquid bilayer, but not for the ordered gel bilayer, indicating that ELPs can destabilize only the disordered bilayer. In the ordered bilayer, ELP chains tend to have a spherical shape and slowly diffuse, while they are extended and diffuse faster in the disordered bilayer, indicating the effect of the bilayer phase on the conformation and diffusivity of ELPs. These findings explain the experimental observation that the ELP-conjugated liposomes are stable at 310 K (ordered phase) but become unstable and release the encapsulated drugs at 315 K (disordered phase), which suggests the effects of ELPs and cholesterols. Since the cholesterol-stabilized bilayer can be destabilized by the extended shaped ELPs only in the disordered phase (not in the ordered phase), the inclusion of cholesterols is required to safely shield drugs at 310 K as well as allow ELPs to disrupt lipids and destabilize the liposomes at 315 K.

Critical role for mesoscale eddy diffusion in supplying oxygen to hypoxic ocean waters

AbstractEstimates of the oceanic lateral eddy diffusion coefficient Aredi vary by more than an order of magnitude, ranging from less than a few hundred m2/s to thousands of m2/s. This uncertainty has first‐order implications for the intensity of oceanic hypoxia, which is poorly simulated by the current generation of Earth System Models. Using satellite‐based estimate of oxygen consumption in hypoxic waters to estimate the required diffusion coefficient for these waters gives a value of order 1000 m2/s. Varying Aredi across a suite of Earth System Models yields a broadly consistent result given a thermocline diapycnal diffusion coefficient of 1 × 10−5 m2/s.

Molecular Weight Dependence of Polymer Chain Mobility within Multilayer Films.

Fluorescence recovery after photobleaching has been applied to determine, to our knowledge for the first time, the molecular weight (Mw) dependence of lateral diffusion of polymer chains within layer-by-layer (LbL) films. As shown by neutron reflectometry, polyelectrolyte multilayers containing polymethacrylic acid (PMAA, Mw/Mn < 1.05) of various molecular weights assembled from solutions of low ionic strengths at pH 4.5, where film growth was linear, showed similar diffusion of PMAA in the direction perpendicular to the film surface. At a salt concentration sufficient for unfreezing electrostatically bonded chains, layer intermixing remained almost unaffected (changes <1.0 nm), while the lateral diffusion coefficient (D) scaled with the PMAA molecular weight as D ∼ Mw-1±0.05.

Phospholipid diffusion coefficients of cushioned model membranes determined via z-scan fluorescence correlation spectroscopy.

Model cellular membranes enable the study of biological processes in a controlled environment and reduce the traditional challenges associated with live or fixed cell studies. However, model membrane systems based on the air/water or oil/solution interface do not allow for incorporation of transmembrane proteins or for the study of protein transport mechanisms. Conversely, a phospholipid bilayer deposited via the Langmuir-Blodgett/Langmuir-Schaefer method on a hydrogel layer is potentially an effective mimic of the cross section of a biological membrane and facilitates both protein incorporation and transport studies. Prior to application, however, such membranes must be fully characterized, particularly with respect to the phospholipid bilayer phase transition temperature. Here we present a detailed characterization of the phase transition temperature of the inner and outer leaflets of a chitosan supported model membrane system. Specifically, the lateral diffusion coefficient of each individual leaflet has been determined as a function of temperature. Measurements were performed utilizing z-scan fluorescence correlation spectroscopy (FCS), a technique that yields calibration-free diffusion information. Analysis via the method of Wawrezinieck and co-workers revealed that phospholipid diffusion changes from raftlike to free diffusion as the temperature is increased-an insight into the dynamic behavior of hydrogel supported membranes not previously reported.

Forming Lipid Bilayer Membrane Arrays on Micropatterned Polyelectrolyte Film Surfaces

A novel method of forming lipid bilayer membrane arrays on micropatterned polyelectrolyte film surfaces is introduced. Polyelectrolyte films were fabricated by the layer-by-layer technique on a silicon oxide surface modified with a 3-aminopropyltriethoxysilane (APTES) monolayer. The surface pK(a) value of the APTES monolayer was determined by cyclic voltammetry to be approximately 5.61, on the basis of which a pH value of 2.0 was chosen for layer-by-layer assembly. Micropatterned polyelectrolyte films were obtained by deep-UV (254 nm) photolysis though a mask. Absorbed fluorescent latex beads were used to visualize the patterned surfaces. Lipid bilayer arrays were fabricated on the micropatterned surfaces by immersing the patterned substrates into a solution containing egg phosphatidylcholine vesicles. Fluorescence recovery after photobleaching studies yielded a lateral diffusion coefficient for probe molecules of 1.31±0.17 μm(2) s(-1) in the bilayer region, and migration of the lipid NBD PE in bilayer lipid membrane arrays was observed in an electric field.

ITO/poly(aniline)/sol-gel glass: An optically transparent, pH-responsive substrate for supported lipid bilayers.

Described here is fabrication of a pH-sensitive, optically transparent transducer composed of a planar indium-tin oxide (ITO) electrode overcoated with a a poly(aniline) (PANI) thin film and a porous sol-gel layer. Adsorption of the PANI film renders the ITO electrode sensitive to pH, whereas the sol-gel spin-coated layer makes the upper surface compatible with fusion of phospholipid vesicles to form a planar supported lipid bilayer (PSLB). The response to changes in the pH of the buffer contacting the sol-gel/PANI/ITO electrode is pseudo-Nernstian with a slope of 52 mV/pH over a pH range of 4-9. Vesicle fusion forms a laterally continuous PSLB on the upper sol-gel surface that is fluid with a lateral lipid diffusion coefficient of 2.2 μm2/s measured by fluorescence recovery after photobleaching. Due to its lateral continuity and lack of defects, the PSLB blocks the pH response of the underlying electrode to changes in the pH of the overlying buffer. This architecture is simpler to fabricate than previously reported ITO electrodes derivatized for PSLB formation, and should be useful for optical monitoring of proton transport across supported membranes derivatized with ionophores and ion channels.

Improved membrane fluidity of ionic polysaccharide bead-supported phospholipid bilayer membrane systems

Supported phospholipid bilayer membranes on polysaccharide-based cationic polymer beads (cationic group: –[OCH2CH(OH)CH2]2N+(CH3)3·X−, 45–165μm in diameter) were prepared using small unilamellar vesicles from mixtures of phosphatidylserine (PS) and phosphatidylcholine (PC). Confocal fluorescence microscopic observations with a fluorescent membrane probe (N-4-nitrobenzo-2-oxa-1,3-diazole-phosphatidylethanolamine) revealed that the phospholipid molecules in the phospholipid-bead complexes were along the outer surface of the beads. The fluidity of the phospholipid bilayer membranes in the PS/PC-bead complexes was investigated by the fluorescence recovery after photobleaching (FRAP) technique. The lateral diffusion coefficients (D) for the PS/PC-bead complexes were lower than that for the 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine giant unilamellar vesicles without solid supports. Such less fluid membranes in the complexes appeared to be due to the immobilization of the phospholipid bilayer membranes by electrostatic attractive forces between PS and the bead. The D values for the PS/PC-bead complexes were dependent on the phospholipid composition; the PS(100mol%)/PC(0mol%)-bead complex had the least fluid membranes among the PS/PC-bead complexes tested in this study. The phospholipid bilayer membranes formed on the polysaccharide-based cationic polymer beads were much more fluid than those on a polystyrene-based one. Furthermore, such fluid phospholipid bilayer membranes formed on the polysaccharide-based cationic polymer bead were maintained for 10 days, even though the complex sample was stood in plain buffer (pH 8.5) at ambient temperature.

Lateral diffusion of lipids separated from rotational and translational diffusion of a fluid large unilamellar vesicle

A new method to separate lateral diffusion of lipids in spherical large unilamellar vesicles from the rotational and the translational diffusion of the vesicle as a whole is proposed. The lateral diffusion coefficient DL is obtained as a time-dependent part of the observed diffusion coefficient in vesicles of 800-nm diameters, by systematically changing the diffusion time interval of the high-field-gradient NMR measurement. Although the lipid is in a confined space, the DL of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine is (1.5±0.6)×10−11m2s−1 in the fluid state at 45°C, more than one order of magnitude faster than the rotational and the translational diffusion coefficients of the vesicle by the hydrodynamic continuum model. The method provides a potential for quantifying the lateral diffusion of lipids and proteins in fluid bilayer vesicles as model cell membranes in a natural manner.

Dynamics and vibrational spectroscopy of water at hydroxylated silica surfaces

In the present study, the structural and dynamical properties of water at hydroxylated silica surfaces are investigated with classical molecular dynamics simulations. Depending on the nature of the interface, water molecules are observed to have well defined ordering and slower dynamics compared to bulk water. These properties include the orientation of water near the surface, reorientational relaxation times, translational diffusion coefficients, planar density distribution and vibrational spectroscopic features. The dynamical and structural features are affected up to approximately equal 6-10 A away from the surface, depending on the properties considered (lateral diffusion coefficient, charge density profile, rotational orientational time). Water molecules at the silica surface show a marked decrease in the diffusion coefficient and an increase in rotational correlation times. The presence of the polar -OH group on the hydroxylated silica surface provides adsorption sites for water with preferred orientations. In addition to the known broadening of the water spectrum in the bonded OH-stretch region for first-layer water molecules, the present simulations find a characteristic band at 1150 cm(-1), which is assigned to the HO(water)-H(SiOH) bending vibration. Because this signal only occurs for water molecules in the first layer, it should be experimentally accessible through surface sensitive techniques such as vibrational sum frequency generation spectroscopy (VSFG).

Kinetics of Diffusion-Mediated DNA Hybridization in Lipid Monolayer Films Determined by Single-Molecule Fluorescence Spectroscopy

We use single-molecule fluorescence microscopy to monitor individual hybridization reactions between membrane-anchored DNA strands, occurring in nanofluidic lipid monolayer films deposited on Teflon AF substrates. The DNA molecules are labeled with different fluorescent dyes, which make it possible to simultaneously monitor the movements of two different molecular species, thus enabling tracking of both reactants and products. We employ lattice diffusion simulations to determine reaction probabilities upon interaction. The observed hybridization rate of the 40-mer DNA was more than 2-fold higher than that of the 20-mer DNA. Since the lateral diffusion coefficient of the two different constructs is nearly identical, the effective molecule radius determines the overall kinetics. This implies that when two DNA molecules approach each other, hydrogen bonding takes place distal from the place where the DNA is anchored to the surface. Strand closure then propagates bidirectionally through a zipper-like mechanism, eventually bringing the lipid anchors together. Comparison with hybridization rates for corresponding DNA sequences in solution reveals that hybridization rates are lower for the lipid-anchored strands and that the dependence on strand length is stronger.

Cyclo-hexa-peptides at the water/cyclohexane interface: a molecular dynamics simulation

Molecular dynamic (MD) simulations have been performed to study the behaviors of ten kinds of cyclo-hexa-peptides (CHPs) composed of amino acids with the diverse hydrophilic/hydrophobic side chains at the water/cyclohexane interface. All the CHPs take the "horse-saddle" conformations at the interface and the hydrophilicity/hydrophobicity of the side chains influences the backbones' structural deformations. The orientations and distributions of the CHPs at the interface and the differences of interaction energies (ΔΔE) between the CHPs and the two liquid phases have been determined. RDF analysis shows that the H-bonds were formed between the O(C) atoms of the CHPs' backbones and H(w) atoms of water molecules. N atoms of the CHPs' backbones formed the H-bonds or van der Waals interactions with the water solvent. It was found that there is a parallel relationship between ΔΔE and the lateral diffusion coefficients (D ( xy )) of the CHPs at the interface. The movements of water molecules close to the interface are confined to some extent, indicating that the dynamics of the CHPs and interfacial water molecules are strongly coupled.

Lateral diffusion of bilayer lipids measured via 31P CODEX NMR

We have employed 31P CODEX (centre-band-only-detection-of-exchange) NMR to measure lateral diffusion coefficients of phospholipids in unilamellar lipid bilayer vesicles consisting of 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC), alone or in mixtures with 30mol% 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG) or cholesterol (CHOL). The lateral diffusion coefficients of POPC and POPG were extracted from experimental CODEX signal decays as a function of increasing mixing time, after accounting for the vesicle's size and size distribution, as determined via dynamic light scattering, and the viscosity of the vesicular suspension, as determined via 1H pulsed field gradient NMR. Lateral diffusion coefficients for POPC and POPG determined in this fashion fell in the range 1.0–3.2×10−12m2s−1 at 10°C, depending on the vesicular composition, in good agreement with accepted values. Thus, two advantages of 31P CODEX NMR for phospholipid lateral diffusion measurements are demonstrated: no labelling of the molecule of interest is necessary, and multiple lateral diffusion coefficients can be measured simultaneously. It is expected that this approach will prove particularly useful in diagnosing heterogeneities in lateral diffusion behaviours, such as might be expected for specific lipid–lipid or lipid–protein interactions, and thermotropic or electrostatically induced phase inhomogeneities.

Impact of signaling microcompartment geometry on GPCR dynamics in live retinal photoreceptors

G protein–coupled receptor (GPCR) cascades rely on membrane protein diffusion for signaling and are generally found in spatially constrained subcellular microcompartments. How the geometry of these microcompartments impacts cascade activities, however, is not understood, primarily because of the inability of current live cell–imaging technologies to resolve these small structures. Here, we examine the dynamics of the GPCR rhodopsin within discrete signaling microcompartments of live photoreceptors using a novel high resolution approach. Rhodopsin fused to green fluorescent protein variants, either enhanced green fluorescent protein (EGFP) or the photoactivatable PAGFP (Rho-E/PAGFP), was expressed transgenically in Xenopus laevis rod photoreceptors, and the geometries of light signaling microcompartments formed by lamellar disc membranes and their incisure clefts were resolved by confocal imaging. Multiphoton fluorescence relaxation after photoconversion experiments were then performed with a Ti–sapphire laser focused to the diffraction limit, which produced small sub–cubic micrometer volumes of photoconverted molecules within the discrete microcompartments. A model of molecular diffusion was developed that allows the geometry of the particular compartment being examined to be specified. This was used to interpret the experimental results. Using this unique approach, we showed that rhodopsin mobility across the disc surface was highly heterogeneous. The overall relaxation of Rho-PAGFP fluorescence photoactivated within a microcompartment was biphasic, with a fast phase lasting several seconds and a slow phase of variable duration that required up to several minutes to reach equilibrium. Local Rho-EGFP diffusion within defined compartments was monotonic, however, with an effective lateral diffusion coefficient Dlat = 0.130 ± 0.012 µm2s−1. Comparison of rhodopsin-PAGFP relaxation time courses with model predictions revealed that microcompartment geometry alone may explain both fast local rhodopsin diffusion and its slow equilibration across the greater disc membrane. Our approach has for the first time allowed direct examination of GPCR dynamics within a live cell signaling microcompartment and a quantitative assessment of the impact of compartment geometry on GPCR activity.

Physicochemical characterization of a monorhamnolipid secreted by Pseudomonas aeruginosa MA01 in aqueous media. An experimental and molecular dynamics study

Given the increasing interest in the characterization of new biosurfactants, in this work we have carried out a physicochemical study of a monorhamnolipid (monoRL) produced by Pseudomonas aeruginosa MA01 in aqueous media. The detailed knowledge of the physicochemical properties of these monoRL biosurfactant is of importance for the validation of this particular P. aeruginosa strain as a useful biosurfactant producer. A pKa value for monoRL of 5.9 was consistently obtained, as well as the indication that the presence of one or two rhamnose rings does not have a notorious influence on the pKa of the carboxyl group. The critical micelle concentration (cmc) of the negatively charged monoRL is dependent on the ionic strength, whereas that of the protonated form is not, whereas the charge of the polar head of monoRL has little effect on the surface area. Dynamic light scattering showed that in the vicinity of the cmc structures with an average diameter of 50nm are present, whereas at concentrations well above the cmc the size increases to about 200nm. Taken together our results show that monoRL presents a monomer-to-micelle transition, which depends on pH and ionic strength, similar to that described before for the diRL species. However the formation of lamellar vesicles described for diRL at pH 7.4, was not observed here. Molecular dynamics (MD) simulations yielded a similar value for the lateral diffusion coefficient of protonated anionic monoRL, indicating that the negative charge does not affect biosurfactant mobility in the monolayer surface. The radial distribution function value is slightly higher for the protonated monoRL; therefore the number of molecules located at a particular distance is somehow higher in the case of the protonated form. On the other hand, it is clearly obtained that the carboxylate group of the anionic form moves more inside the aqueous phase as compared to the carboxyl group of the protonated form. The results obtained correspond to the expected behaviour for a biosurfactant molecule in relation to the dependence of protonation state and micelle formation, and therefore the molecular dynamics simulation appears to describe properly our molecular systems.

Model of lateral diffusion in ultrathin layered films

We consider the diffusion of markers in a layered medium, with the lateral diffusion coefficient being the function of hight. We show that the probability density of the lateral displacements follows a one-dimensional Batchelor’s equation with time-dependent diffusion coefficient governed by the particles’ redistribution in height. For the film of a finite thickness the resulting mean squared displacement exhibits superdiffusion at short times and crosses over to normal diffusion at long times. The approach is used for a description of experimental results on inhomogeneous molecular diffusion in thin liquid films deposited on solid surfaces.

Fluorescence microscopic characterization of ionic polymer bead-supported phospholipid bilayer membrane systems

Supported phospholipid membrane structures on cationic organic polymer beads were prepared using mixtures of dioleoylphosphatidylserine (PS) and egg yolk phosphatidylcholine (PC). Confocal fluorescence microscopic observations using a fluorescent membrane probe (N-4-nitrobenzo-2-oxa-1,3-diazole-phosphatidylethanolamine) revealed that the phospholipid molecules in the PS/PC-bead complexes were along the outer surface of the beads, but not inside the beads. The anionic PS on the most outer surface of the PS/PC-bead complexes was responsible for the binding of a positively charged macromolecule, rhodamine isothiocyanate dextran (Mw 70,000) by electrostatic attractive forces. The fluidity of the membranes in the PS/PC-bead complexes was investigated by the fluorescence recovery after a photobleaching technique. The lateral diffusion coefficients (D) for the PS/PC-bead complexes were one-half or less than that for 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine giant unilamellar vesicles without solid supporting materials. Such a constrain of the phospholipid bilayer membrane in the complexes appeared to be due to its immobilization on the cationic polymer bead by electrostatic attractive forces between the PS and ammonium group on the surface of the bead. The D values for the complexes were dependent on the phospholipid composition; the PS(25mol%)/PC(75mol%)-bead complex produced a more fluid membrane than the PS(50mol%)/PC(50mol%)-bead one. Thus, the fluidity of the phospholipid bilayer membranes formed on the cationic polymer beads was significantly affected by the anionic phospholipid fraction used for the preparation of the complexes.

Effect of membrane tension on the physical properties of DOPC lipid bilayer membrane

Molecular dynamics simulations of a dioleoylphosphocholine (DOPC) lipid bilayer were performed to explore its mechanosensitivity. Variations in the bilayer properties, such as area per lipid, volume, thickness, hydration depth (HD), hydration thickness (HT), lateral diffusion coefficient, and changes in lipid structural order were computed in the membrane tension range 0 to 15dyn/cm. We determined that an increase in membrane tension results in a decrease in the bilayer thickness and HD of ~5% and ~5.7% respectively, whereas area per lipid, volume, and HT/HD increased by 6.8%, 2.4%, and 5% respectively. The changes in lipid conformation and orientation were characterized using orientational (S2) and deuterium (SCD) order parameters. Upon increase of membrane tension both order parameters indicated an increase in lipid disorder by 10–20%, mostly in the tail end region of the hydrophobic chains. The effect of membrane tension on lipid lateral diffusion in the DOPC bilayer was analyzed on three different time scales corresponding to inertial motion, anomalous diffusion and normal diffusion. The results showed that lateral diffusion of lipid molecules is anomalous in nature due to the non-exponential distribution of waiting times. The anomalous and normal diffusion coefficients increased by 20% and 52% when the membrane tension changed from 0 to 15dyn/cm, respectively. In conclusion, our studies showed that membrane tension causes relatively significant changes in the area per lipid, volume, polarity, membrane thickness, and fluidity of the membrane suggesting multiple mechanisms by which mechanical perturbation of the membrane could trigger mechanosensitive response in cells.

Lipid exchange between membranes: Effects of membrane surface charge, composition, and curvature

Intermembrane lipid exchange is critical to membrane functions and pharmaceutical applications. The exchange process is not fully understood and it is explored by quartz crystal microbalance with dissipation monitor method in this research. It is found that intermembrane lipid exchange is accelerated with the decrease of vesicle size and the increase of charge and liquid crystalline lipid composition ratio. Vesicle adsorption rate, membrane lateral pressure gradient, and lipid lateral diffusion coefficient are inferred to be critical in deciding the lipid exchange kinetics between membranes. Besides that, the membrane contact situation during lipid exchange is also studied. The maximum total membrane contact area is found to increase with the decrease of vesicle size, charged and liquid crystalline lipid composition ratio. A competition mechanism between the vesicle adsorption rate and the intermembrane lipid exchange rate was proposed to control the maximum total membrane contact area.