We use a long, all-atom molecular dynamics (MD) simulation combined with theoretical modeling to investigate the dynamics of selected lipid atoms and lipid molecules in a hydrated diyristoyl-phosphatidylcholine (DMPC) lipid bilayer. From the analysis of a 0.1 $μ$s MD trajectory we find that the time evolution of the mean square displacement, [δ{r}(t)]^2, of lipid atoms and molecules exhibits three well separated dynamical regions: (i) ballistic, with [δ{r}(t)]^2 ~ t^2 for t < 10 fs; (ii) subdiffusive, with [δ{r}(t)]^2 ~ t^β with β<1, for 10 ps < t < 10 ns; and (iii) Fickian diffusion, with [δ{r}(t)]^2 ~ t for t > 30 ns. We propose a memory function approach for calculating [δ{r}(t)]^2 over the entire time range extending from the ballistic to the Fickian diffusion regimes. The results are in very good agreement with the ones from the MD simulations. We also examine the implications of the presence of the subdiffusive dynamics of lipids on the self-intermediate scattering function and the incoherent dynamics structure factor measured in neutron scattering experiments.
We report the effect of lipid head-group dipole orientation on phase behaviour of phospholipid assembly. The work explains molecular-scale mechanism of ion-lipid, anesthetic-lipid interactions where reorientation of dipoles play important role in membrane potential modification. Molecular Dynamics simulations are performed to analyse structure-property relationship and dynamical behaviour of lipid biomembranes considering coarse-grained model interactions.
Water-phospholipid interactions at the lipid bilayer/water interfaces are of essential importance for the dynamics, stability and function of biological membrane, and are also strongly associated with numerous biological processes at the interfaces of lipid bilayers. Various force fields, such as the united-atom Berger force field, its two improved versions by Kukol and by Poger, and the all-atom Slipid force field developed recently, can be applied to simulating the structures of lipid bilayer, with their structural predictions in good agreement with experimental data. In this work, we show t…
We report a high energy-resolution neutron backscattering study, combined with in-situ diffraction, to investigate slow molecular motions on nanosecond time scales in the fluid phase of phospholipid bilayers of 1,2-dimyristoyl-sn-glycero-3-phoshatidylcholine (DMPC) and DMPC/40% cholesterol (wt/wt). A cooperative structural relaxation process was observed. From the in-plane scattering vector dependence of the relaxation rates in hydrogenated and deuterated samples, combined with results from a 0.1 microsecond long all atom molecular dynamics simulation, it is concluded that correlated dynamics …
Combining extensive molecular dynamics simulations of lipid bilayer systems of varying chemical composition with single-trajectory analyses we systematically elucidate the stochastic nature of the lipid motion. We observe subdiffusion over more than four orders of magnitude in time, clearly stretching into the sub-microsecond domain. The lipid motion delicately depends on the lipid chemistry, the lipid phase, and especially on the presence of cholesterol. We demonstrate that fractional Langevin equation motion universally describes the lipid motion in all phases including the gel phase, and in…
The hydration process of multi-stacked phospholipid bilayers to form giant vesicles was investigated by time-resolved small angle X-ray scattering. The hydration of lipids in the liquid-crystalline phase was found to proceed in two stages. In the early stage, until about 100 s after hydration, lipid bilayers on a solid substrate swell about 12 $\rmÅ$ and reach a quasi-stable state. In the late stage, after several hundreds of seconds, lipid bilayers gradually peel off from the stack. On the other hand, in the case of a lipid in the gel phase, only the early stage is observed. These behaviors c…
Membrane fluidity, well-known to be essential for cell functions, is obviously affected by copper. However, the underlying mechanism is still far from being understood, especially on the atomic level. Here, we unexpectedly observed that a decrease in phospholipid (PL) bilayer fluidity caused by Cu2+ was much more significant than those induced by Zn2+ and Ca2+, while a comparable reduction occurred in the last two ions. This finding clearly disagrees with the placement in the periodic table of Cu just next to Zn and far from Ca. The physical nature was revealed to be a special attraction betwe…
Diffusion in biological membranes is seldom simply Brownian motion; instead, the rate of diffusion is dependent on the timescale of observation and so is often described as anomalous. In order to help better understand this phenomenon, model systems are needed where the anomalous subdiffusion of the lipid bilayer can be tuned and quantified. We recently demonstrated one such model by controlling the excluded area fraction in supported lipid bilayers (SLBs) through the incorporation of lipids derivatised with polyethylene glycol. Here we extend this work, using urea to induce anomalous subdiffu…
Cholesterol (CHOL) drives lipid segregation and is thus a key player for the formation of lipid rafts and followingly for the ability of a cell to, e.g., enable selective agglomeration of proteins. The lipid segregation is driven by cholesterol's affinity for saturated lipids, which stands directly in relation to the ability of cholesterol to order the individual phospholipid (PL) acyl chains. In this work, Molecular Dynamics simulations of DPPC (Dipalmitoylphosphatidylcholine, saturated lipid) and DLiPC (Dilineoylphosphatidylcholine, unsaturated lipid) mixtures with cholesterol are used to el…
We studied the adsorption of a charged protein onto an oppositely charged membrane, composed of mobile phospholipids of differing valence, using a statistical-thermodynamical approach. A two-block model was employed, one block corresponding to the protein-affected region on the membrane, referred to as the adsorption domain, and the other to the unaffected remainder of the membrane. We calculated the protein-induced lipid rearrangement in the adsorption domain as arising from the interplay between the electrostatic interactions in the system and the mixing entropy of the lipids. Equating the e…
We study the effect of cholesterol on the structure of dipalmitoylphosphatidylcholine (DPPC) phospholipid bilayers. Using extensive molecular dynamics computer simulations at atomistic resolution we observe and quantify several structural changes upon increasing cholesterol content that are collectively known as the condensing effect: a thickening of the bilayer, an increase in lipid tail order, and a decrease in lateral area. We also observe a change in leaflet interdigitation and a lack thereof in the distributions of DPPC head group orientations. These results, obtained over a wide range of…
We address the relationship between membrane microheterogeneity and anomalous subdiffusion in cell membranes by carrying out Monte Carlo simulations of two-component lipid membranes. We find that near-critical fluctuations in the membrane lead to transient subdiffusion, while membrane-cytoskeleton interaction strongly affects phase separation, enhances subdiffusion, and eventually leads to hop diffusion of lipids. Thus, we present a minimum realistic model for membrane rafts showing the features of both microscopic phase separation and subdiffusion.
Lipid monolayers have been shown to represent a powerful tool in studying mechanical and thermodynamic properties of lipid membranes as well as their interaction with proteins. Using Einstein's theory of fluctuations we here demonstrate, that an experimentally derived linear relationship both between transition entropy S and area A as well as between transition entropy and charge q implies a linear relationships between compressibility κ_T, heat capacity c_π, thermal expansion coefficient α_T and electric capacity CT. We demonstrate that these couplings have strong predictive power as they all…
A method for determining permeability of phospholipid bilayer based on the osmotic swelling of micrometer-sized giant unilamellar vesicles (GUVs) is presented as an alternative to the two established techniques, dynamic light scattering on liposome suspension, and electrical measurements on planar lipid bilayers. In the described technique, an individual GUV is transferred using a micropipette from a sucrose/glucose solution into an isomolar solution containing the solute under investigation. Throughout the experiment, vesicle cross-section is monitored and recorded using a digital camera moun…
Annexins are a family of proteins that bind to anionic phospholipid membranes in a Ca2+-dependent manner. Annexin A2 forms heterotetramers (Anx A2t) with the S100A10 (p11) protein dimer. The tetramer is capable of bridging phospholipid membranes and it has been suggested to play a role in Ca2+-dependent exocytosis and cell-cell adhesion of metastatic cells. Here, we employ x-ray reflectivity measurements to resolve the conformation of Anx A2t upon Ca2+-dependent binding to single supported lipid bilayers (SLBs) composed of different mixtures of anionic (POPS) and neutral (POPC) phospholipids. …
Water molecules play an important role in providing unique environments for biological reactions on cell membranes. It is widely believed that water molecules form bridges that connect lipid molecules and stabilize cell membranes. Using all-atom molecular dynamics simulations, we show that translational and rotational diffusion of water molecules on lipid membrane surfaces exhibit subdiffusion. Moreover, we provide evidence that both divergent mean trapping time (continuous-time random walk) and long-correlated noise (fractional Brownian motion) contribute to this subdiffusion. These results s…
Lipid membranes in a physiological context cannot be understood without taking into account their mobile environment. Here, we report on a high energy-resolution neutron backscattering study to investigate slow motions on nanosecond time scales in highly oriented solid supported phospholipid bilayers of the model system DMPC -d54 (deuterated 1,2-dimyristoyl-sn-glycero-3-phoshatidylcholine). This technique allows discriminating the Q-dependent onset of mobility and provides a benchmark test regarding the feasibility of dynamical neutron scattering investigations on these sample systems. Apart f…
We present the derivation of a new model to describe neutron spin echo spectroscopy and quasi-elastic neutron scattering data on liposomes. We compare the new model with existing approaches and benchmark it with experimental data. The analysis indicates the importance of including all major contributions into modeling of the intermediate scattering function. Simultaneous analysis of the experimental data on lipids with full contrast and tail contrast matched samples, reveals highly confined lipid tail motion. A comparison of their dynamics demonstrates the statistical independ-ence of tail-mot…
In this paper the problem of surface charge of the lipid membrane immersed in the physiological solution is considered. It is shown that both side of the bilayer phospholipid membrane surface are negatively charged. A self-consistent model of the potential in solution is developed, and a stationary charge density on the membrane surface is found. It is shown that the ions of the surface charge are in a relatively deep (as compared to kBT) potential wells, which are localized near the dipole heads of phospholipid membrane. It makes impossible for ions to slip along the membrane surface. Simple …
Cholesterol (CHOL) is one of the most important components of plasma membranes of higher cells and one of the main factors for the formation of (nano)domains. In this work, molecular dynamics simulations of mixtures of CHOL with DPPC (saturated lipid) and DLiPC (unsaturated lipid) as standard phospholipids (PLs) are presented in a wide range of CHOL concentrations. The key idea is to systematically extract all structural and enthalpic properties relevant to the formulation of a lattice model of these systems and express them in dependence of the acyl chain order parameters. Detailed interpreta…
Ultra-long-chain fatty acids (ULCFAs) are biosynthesized in the restricted tissues such as retina, testis, and skin. The conformation of a single ULCFA, in which the sn-1 unsaturated chain has 32 carbons, in three types of tensionless phospholipid bilayers is studied by molecular dynamics simulations. It is found that the ultra-long tail of the ULCFA flips between two leaflets and fluctuates among an elongation into the opposite leaflet, lying between two leaflets, and turning back. As the number ratio of lipids in the opposite leaflet increases, the ratio of the elongated shape linearly decre…
The emerging diffusive dynamics in many complex systems shows a characteristic crossover behaviour from anomalous to normal diffusion which is otherwise fitted by two independent power-laws. A prominent example for a subdiffusive-diffusive crossover are viscoelastic systems such as lipid bilayer membranes, while superdiffusive-diffusive crossovers occur in systems of actively moving biological cells. We here consider the general dynamics of a stochastic particle driven by so-called tempered fractional Gaussian noise, that is noise with Gaussian amplitude and power-law correlations, which are c…
We summarize and compare recent Molecular Dynamics simulations on the interactions of dipalmitoylphosphatidylcholine (DPPC) bilayers in the liquid crystalline phase with a number of small molecules including trehalose, a disaccharide of glucose, alcohols, and dimethylsulfoxide (DMSO). The sugar molecules tend to stabilize the structure of the bilayer as they bridge adjacent lipid headgroups. They do not strongly change the structure of the bilayer. Alcohols and DMSO destabilize the bilayer as they increase its area per molecule in the bilayer plane and decrease the order parameter. Alcohols ha…
We use coarse grained molecular dynamics simulations to investigate diffusion properties of sheared lipid membranes with embedded transmembrane proteins. In membranes without proteins, we find normal in-plane diffusion of lipids in all flow conditions. Protein embedded membranes behave quite differently: by imposing a simple shear flow and sliding the monolayers of the membrane over each other, the motion of protein clusters becomes strongly superdiffusive in the shear direction. In such a circumstance, subdiffusion regime is predominant perpendicular to the flow. We show that superdiffusion i…
Surface Plasmon Resonance (SPR) is an important bio-sensing technique for real-time label-free detection. However, it is pivotal to optimize various parameters of the sensor configuration for efficient and highly sensitive sensing. To that effect, we focus on optimizing two different SPR structures -- the basic Kretschmann configuration and narrow groove grating. Our analysis aims to detect two different types of lipids known as phospholipid and eggyolk, which are used as analyte (sensing layer) and two different types of proteins namely tryptophan and bovine serum albumin (BSA) are used as li…
The hydrodynamic drag at a lipid bilayer surface determines in part the flow properties of suspensions of cells and liposomes. Given the fluidity of lipid bilayers, it is not obvious a priori whether solid-like no-slip, liquid-like no-stress, or intermediate boundary conditions apply at the water-bilayer interface. Though no-slip conditions have been widely assumed for many decades, this fundamental aspect of membrane rheology has, to our knowledge, never been directly measured for free bilayers. We applied light sheet fluorescence microscopy to image freely diffusing phospholipid vesicles and…
Combining extensive single particle tracking microscopy data of endogenous lipid granules in living fission yeast cells with analytical results we show evidence for anomalous diffusion and weak ergodicity breaking. Namely we demonstrate that at short times the granules perform subdiffusion according to the laws of continuous time random walk theory. The associated violation of ergodicity leads to a characteristic turnover between two scaling regimes of the time averaged mean squared displacement. At longer times the granule motion is consistent with fractional Brownian motion.
Droplet interface bilayers are a convenient model system to study the physio-chemical properties of phospholipid bilayers, the major component of the cell membrane. The mechanical response of these bilayers to various external mechanical stimuli is an active area of research due to implications for cellular viability and development of artificial cells. In this manuscript we characterize the separation mechanics of droplet interface bilayers under step strain using a combination of experiments and numerical modeling. Initially, we show that the bilayer surface energy can be obtained using prin…
By means of lattice-based Monte Carlo simulations, we address properties of two-component lipid membranes on the experimentally relevant spatial scales of order of a micrometer and time intervals of order of a second, using DMPC/DSPC lipid mixtures as a model system. Our large-scale simulations allowed us to obtain important results previously not reported in simulation studies of lipid membranes. We find that, within a certain range of lipid compositions, the phase transition from the fluid phase to the fluid-gel phase coexistence proceeds via near-critical fluctuations, while for other lipid…
Sterols have been ascribed a major role in the organization of biological membranes, in particular for the formation of liquid ordered domains in complex lipid mixtures. Here, we employed molecular dynamics simulations to compare the effects of cholesterol and ergosterol as the major sterol of mammalian and fungal cells, respectively, on binary mixtures with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) as a proxy for saturated lipids. In agreement with previous work, we observe that the addition of sterol molecules modifies the order of DPPC both in the gel phase and in the liquid phase.…
An accurate description of the structure and dynamics of interfacial water is essential for phospholipid membranes, since it determines their function and their interaction with other molecules. Here we consider water confined in stacked membranes with hydration from poor to complete, as observed in a number of biological systems. Experiments show that the dynamics of water slows down dramatically when the hydration level is reduced. All-atom molecular dynamics simulations identify three (inner, hydration and outer) regions, within a distance of approximately 1 nm from the membrane, where wate…
Measurements of protein motion in living cells and membranes consistently report transient anomalous diffusion (subdiffusion) which converges back to a Brownian motion with reduced diffusion coefficient at long times, after the anomalous diffusion regime. Therefore, slowed-down Brownian motion could be considered the macroscopic limit of transient anomalous diffusion. On the other hand, membranes are also heterogeneous media in which Brownian motion may be locally slowed-down due to variations in lipid composition. Here, we investigate whether both situations lead to a similar behavior for the…
