A tethered vesicle, which consists of a cylindrical membrane tube and a spherical vesicle, is produced by a mechanical force that is experimentally imposed by optical tweezers and a micropipette. This tethered vesicle is employed for examining the curvature sensing of curvature-inducing proteins. In this study, we clarify how the binding of proteins with a laterally isotropic spontaneous curvature senses and generates the membrane curvatures of the tethered vesicle using mean-field theory and meshless membrane simulation. The force-dependence curves of the protein density in the membrane tube and the tube curvature are reflection symmetric and point symmetric, respectively, from the force point, in which the tube has a sensing curvature. The bending rigidity and spontaneous curvature of the bound proteins can be estimated from these force-dependence curves. First-order transitions can occur between low and high protein densities in the tube at both low and high force amplitudes. The simulation results of the homogeneous phases agree very well with the theoretical predictions. In addition, beaded-necklace-like tubes with microphase separation are found in the simulation.
We investigate the electrostatics of a partially formed, charged spherical shell in a salt solution. We solve the problem numerically at the Poisson-Boltzmann level and analytically in the Debye-Huckel regime. From the results on energetics of partially formed shells we examine the stability of tethered (crystalline) and fluid shells towards rupture. We clearly delineate different regimes of stability towards rupture, where, for fluid shells, we also include the effects of bending elasticity of the shells. Our analysis shows how charging of the shell induces its instability towards rupture but…
We report results concerning the destabilisation of supported phospholipid bilayers in a well-defined geometry. When heating up supported phospholipid membranes deposited on highly hydrophilic glass slides from room temperature (i.e. with lipids in the gel phase), unbinding was observed around the main gel to fluid transition temperature of the lipids. It lead to the formation of relatively monodisperse vesicles, of which most remained tethered to the supported bilayer. We interpret these observations in terms of a sharp decrease of the bending rigidity modulus $κ$ in the transition region, co…
Estimation of anisotropic bending rigidities and spontaneous curvatures of crescent curvature-inducing proteins from tethered-vesicle experimental data
本研究基于系绳囊泡实验数据，利用各向异性弯曲能量平均场理论估算 BAR 蛋白的弯曲刚度与自发曲率，发现各向异性模型能更好拟合 I-BAR 数据，而 N-BAR 的拟合偏差可能源于其簇集形成。
Vesicle budding induced by protein binding that generates an isotropic spontaneous curvature is studied using a mean-field theory. Many spherical buds are formed via protein binding. As the binding chemical potential increases, the proteins first bind to the buds and then to the remainder of the vesicle. For a high spontaneous curvature and/or high bending rigidity of the bound membrane, it is found that a first-order transition occurs between a small number of large buds and a large number of small buds. These two states coexist around the transition point. The proposed scheme is simple and e…
We found that three types of tethered surface model undergo a first-order phase transition between the smooth and the crumpled phase. The first and the third are discrete models of Helfrich, Polyakov, and Kleinert, and the second is that of Nambu and Goto. These are curvature models for biological membranes including artificial vesicles. The results obtained in this paper indicate that the first-order phase transition is universal in the sense that the order of the transition is independent of discretization of the Hamiltonian for the tethered surface model.
Curvature-inducing proteins containing a Bin/Amphiphysin/Rvs domain often have intrinsically disordered domains. Recent experiments have shown that these disordered chains enhance curvature sensing and generation. Here, we report on the modification of protein-membrane interactions by disordered chains using meshless membrane simulations. The protein and bound membrane are modeled together as a chiral crescent protein rod with two excluded-volume chains. As the chain length increases, the repulsion between them reduces the cluster size of the proteins. It induces spindle-shaped vesicles and a …
A phase field model for dealing with shape instabilities in fluid membrane vesicles is presented. This model takes into account the Canham-Helfrich bending energy with spontaneous curvature. A dynamic equation for the phase-field is also derived. With this model it is possible to see the vesicle shape deformation dynamically, when some external agent instabilizes the membrane, for instance, inducing an inhomogeneous spontaneous curvature. The numerical scheme used is detailed and some stationary shapes are shown together with a shape diagram for vesicles of spherical topology and no spontaneou…
The assembly of curved protein rods on fluid membranes is studied using implicit-solvent meshless membrane simulations. As the rod curvature increases, the rods on a membrane tube assemble along the azimuthal direction first and subsequently along the longitudinal direction. Here, we show that both transition curvatures decrease with increasing rod stiffness. For comparison, curvature-inducing isotropic inclusions are also simulated. When the isotropic inclusions have the same bending rigidity as the other membrane regions, the inclusions are uniformly distributed on the membrane tubes and ves…
Lipid bilayer membranes are the fundamental biological barriers that permit life. The bilayer dynamics largely participates in orchestrating cellular workings and is characterized by substantial stability together with extreme plasticity that allows controlled morphological/topological changes. Modeling and understanding the topological change of vesicle-like membrane at the scale of a full cell has proved an elusive aim. We propose and discuss here a continuum model able to encompass the fusion/fission transition of a bilayer membrane at the scale of a Large Unilamellar Vesicle and evaluate t…
We review the theoretical analyses and simulations of the interactions between curvature-inducing proteins and biomembranes. Laterally isotropic proteins induce spherical budding, whereas anisotropic proteins, such as Bin/Amphiphysin/Rvs (BAR) superfamily proteins, induce tabulation. Both types of proteins can sense the membrane curvature. We describe the theoretical analyses of various transitions of protein binding accompanied by a change in various properties, such as the number of buds, the radius of membrane tubes, and the nematic order of anisotropic proteins. Moreover, we explain the me…
Short DNA linkers are increasingly being exploited for driving specific self-assembly of Brownian objects. DNA-functionalised colloids can assemble into ordered or amorphous materials with tailored morphology. Recently, the same approach has been applied to compliant units, including emulsion droplets and lipid vesicles. The liquid structure of these substrates introduces new degrees of freedom: the tethers can diffuse and rearrange, radically changing the physics of the interactions. Unlike droplets, vesicles are extremely deformable and DNA-mediated adhesion causes significant shape adjustme…
We grafted polyacrylic acid brushes containing cysteine side chains at a defined surface density on planar lipid membranes. Specular X-ray reflectivity data indicated that the addition of Cd2+ ions induces the compaction of the polymer brush layer and modulates the adhesion of lipid vesicles. The critical threshold level inducing the switch from non-wetting to partial wetting state, [Cd2+] = 0.25 mM, was determined by microinterferometry. The interactions between vesicles and brushes were evaluated by height fluctuations of the membrane in contact with brushes and the shape of vesicles near th…
Spatial organisation is a hallmark of all living cells, and recreating it in model systems is a necessary step in the creation of synthetic cells. It is therefore of both fundamental and practical interest to better understand the basic mechanisms underlying spatial organisation in cells. In this work, we use a continuum model of membrane and protein dynamics to study the behaviour of curvature-inducing proteins on membranes of spherical shape, such as living cells or lipid vesicles. We show that the interplay between curvature energy, entropic forces, and the geometric constraints on the memb…
The spatio-temporal organization of proteins and the associated morphological changes in membranes are of importance in cell signaling. Several mechanisms that promote the aggregation of proteins at low cell surface concentrations have been investigated in the past. We show, using Monte Carlo simulations, that the affinity of proteins for specific lipids can hasten its aggregation kinetics. The lipid membrane is modeled as a dynamically triangulated surface with the proteins defined as in-plane fields at the vertices. We show that, even at low protein concentrations, strong lipid-protein inter…
The reaction-diffusion waves of proteins are known to be involved in fundamental cellular functions, such as cell migration, cell division, and vesicular transportation. In some of these phenomena, pattern formation on the membranes is induced by the coupling between membrane deformation and the reaction-diffusion system through curvature-inducing proteins that bend the biological membranes. Although the membrane shape and the dynamics of the curvature-inducing proteins affect each other in these systems, the effect of such mechanochemical feedback loops on the waves has not been studied in de…
In living cells, membrane morphology is regulated by various proteins. Many membrane reshaping proteins contain a Bin/Amphiphysin/Rvs (BAR) domain, which consists of a banana-shaped rod. The BAR domain bends the biomembrane along the rod axis and the features of this anisotropic bending have recently been studied. Here, we report on the role of the BAR protein rods in inducing membrane tubulation, using large-scale coarse-grained simulations. We reveal that a small spontaneous side curvature perpendicular to the rod can drastically alter the tubulation dynamics at high protein density, whereas…
Multivalent particles bind to targets via many independent ligand-receptor bonding interactions. This microscopic design spans length scales in both synthetic and biological systems. Classic examples include interactions between cells, virus binding, synthetic ligand-coated micrometer-scale vesicles or smaller nano-particles, functionalised polymers, and toxins. Equilibrium multivalent binding is a continuous yet super-selective transition with respect to the number of ligands and receptors involved in the interaction. Increasing the ligand or receptor density on the two particles leads to sha…
Simulating Curved Lipid Membranes Using Anchored Frozen Patches
Department of Materials Science and Engineering, Grainger College of Engineering, University of Illinois Urbana-Champaign（伊利诺伊大学厄巴纳-香槟分校格雷恩工程学院材料科学与工程系）
