Membrane phase behavior induced by the binding of curvature-inducing proteins is studied by a combination of analytical and numerical approaches. In thermal equilibrium under the detailed balance between binding and unbinding, the membrane exhibits three phases: an unbound uniform flat phase (U), a bound uniform flat phase (B), and a separated/corrugated phase (SC). In the SC phase, the bound proteins form hexagonally-ordered bowl-shaped domains. The transitions between the U and SC phases and between the B and SC phases are second order and first order, respectively. At a small spontaneous curvature of the protein or high surface tension, the transition between B and SC phases becomes continuous. Moreover, a first-order transition between the U and B phases is found at zero spontaneous curvature driven by the Casimir-like interactions between rigid proteins. Furthermore, nonequilibrium dynamics is investigated by the addition of active binding and unbinding at a constant rate. The active binding and unbinding processes alter the stability of the SC phase.
The domain formation of curvature-inducing molecules, such as peripheral or transmembrane proteins and conical surfactants, is studied in thermal equilibrium and nonequilibrium steady states using meshless membrane simulations. These molecules can bind onto both surfaces of a bilayer membrane and also move to the opposite leaflet by a flip-flop. In symmetric conditions for the two leaflets, the membrane domains form checkerboard patterns in addition to stripe and spot patterns. The unbound membrane stabilizes the vertices of the checkerboard. In asymmetric conditions, the domains form kagome-l…
Living cells employ excitable reaction-diffusion waves for internal cellular functions, in which curvature-inducing proteins are often involved. However, the role of their mechanochemical coupling is not well understood. Here, we report the membrane deformation induced by the excitable reaction-diffusion waves of curvature-inducing proteins and the alternation in the waves due to the deformation, using a coarse-grained simulation of tubular membranes with a modified FitzHugh--Nagumo model. Protein-propagating waves deform tubular membranes, and large deformations induce budding and erase waves…
Two-dimensional crystalline membranes have recently been realized experimentally in such systems as graphene and molybdenum disulfide, sparking a resurgence in interest in their statistical properties. Thermal fluctuations can significantly affect the effective mechanical properties of properly thermalized membranes, renormalizing both bending rigidity and elastic moduli so that in particular they become stiffer to bending than their bare bending rigidity would suggest. We use molecular dynamics simulations to examine how the mechanical behavior of thermalized two-dimensional clamped ribbons (…
The mechanical properties of thermally excited two-dimensional crystalline membranes can depend dramatically on their geometry and topology. A particularly relevant example is the effect on the crumpling transition of holes in the membrane. Here we use molecular dynamics simulations to study the case of elastic frames (sheets with a single large hole in the center) and find that the system approaches the crumpled phase through a sequence of origami-like folds at decreasing length scales when temperature is increased. We use normal-normal correlation functions to quantify the temperature-depend…
The shapes of cell membranes are largely regulated by membrane associated, curvature active, proteins. We use a numerical model of the membrane with elongated membrane inclusions, recently developed by us, which posses spontaneous directional curvatures that could be different along and perpendicular to its long axis. We show that, due to membrane mediated interactions these curvature inducing membrane nematogens can oligomerize spontaneously, even at low concentrations, and change the local shape of the membrane. We demonstrate that for a large group of such inclusions, where the two spontane…
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…
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 phenomenological Landau elasticity for the shape, dilation, and lipid-tilt of bilayer membranes is developed. The shape mode couples with the sum of the monolayers' tilt, while the dilation mode couples with the difference of the monolayers' tilts. Interactions among membrane inclusions within regular arrays are discussed. Inclusions modifying the membrane thickness and/or inducing a tilt-difference due to their convex or concave shape yield a dilation-induced attraction and a tilt-difference-induced repulsion. The resulting interaction can stabilize 2D crystal phases, with the possible coex…
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…
Bin/Amphiphysin/Rvs superfamily proteins and other curvature-inducing proteins have anisotropic shapes and anisotropically bend biomembrane. Here, we report how the anisotropic proteins bind the membrane tube and are orientationally ordered using mean-field theory including an orientation-dependent excluded volume. The proteins exhibit a second-order or first-order nematic transition with increasing protein density depending on the radius of the membrane tube. The tube curvatures for the maximum protein binding and orientational order are different and varied by the protein density and rigidit…
Curvature-sensing and curvature-remodeling proteins are known to reshape cell membranes, and this remodeling event is essential for key biophysical processes such as tubulation, exocytosis, and endocytosis. Curvature-inducing proteins can act as curvature sensors as well as induce curvature in cell membranes to stabilize emergent high curvature, non-spherical, structures such as tubules, discs, and caveolae. A definitive understanding of the interplay between protein recruitment and migration, the evolution of membrane curvature, and membrane morphological transitions is emerging but remains i…
The interplay of membrane proteins is vital for many biological processes, such as cellular transport, cell division, and signal transduction between nerve cells. Theoretical considerations have led to the idea that the membrane itself mediates protein self-organization in these processes through minimization of membrane curvature energy. Here, we present a combined experimental and numerical study in which we quantify these interactions directly for the first time. In our experimental model system we control the deformation of a lipid membrane by adhering colloidal particles. Using confocal m…
There are a great many proteins that localize to and collectively generate curvature in biological fluid membranes. We study changes in the topology of fluid membranes due to the presence of highly anisotropic, curvature-inducing proteins. Generically, we find a surprisingly rich phase diagram with phases of both positive and negative Gaussian curvature. As a concrete example modeled on experiments, we find that a lamellar phase in a negative Gaussian curvature regime exhibits a propensity to form screw dislocations of definite burgers scalar but of both chirality. The induced curvature depend…
Biological membranes constitute boundaries of cells and cell organelles. Physico-chemical mechanisms at the atomic scale are dictated by protein-lipid interaction strength, lipid composition, lipid distribution in the vicinity of the protein, shape and amino acid composition of the protein, and its amino acid contents. The specificity of molecular interactions together with the cooperativity of multiple proteins induce and stabilize complex membrane shapes at the mesoscale. These shapes span a wide spectrum ranging from the spherical plasma membrane to the complex cisternae of the Golgi appara…
We investigate the phenomenon of protein induced tubulation of lipid bilayer membranes within a continuum framework using Monte Carlo simulations coupled with the Widom insertion technique to compute excess chemical potentials. Tubular morphologies are spontaneously formed when the density and the curvature-field strength of the membrane bound proteins exceed their respective thresholds and this transition is marked by a sharp drop in the excess chemical potential. We find that the planar to tubular transition can be described by a micellar model and that the corresponding free energy barrier …
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 …
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…
A theory is presented for the membrane junction separation induced by the adhesion between two biomimetic membranes that contain two different types of anchored junctions (receptor/ligand complexes). The analysis shows that several mechanisms contribute to the membrane junction separation. These mechanisms include (i) the height difference between type-1 and type-2 junctions is the main factor which drives the junction separation, (ii) when type-1 and type-2 junctions have different rigidities against stretch and compression, the ``softer'' junctions are the ``favored'' species, and the aggreg…
Active assembly and non-reciprocal dynamics of elastic membranes
The Martin Fisher School of Physics, Brandeis University（布兰迪斯大学马丁·费舍尔物理学院）；Department of Physics, University of California at Santa Barbara（加州大学圣塔芭芭拉分校物理系）；School of Physics, Georgia Institute of Technology（佐治亚理工学院物理学院）；Kavli Institute of Theoretical Physics（卡弗里理论物理研究所）；Leinweber Institute for Theoretical Physics, University of Chicago（芝加哥大学莱因韦伯理论物理研究所）；James Frank Institute, University of Chicago（芝加哥大学詹姆斯·弗兰克研究所）
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…
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…
Thermalized elastic membranes without distant self-avoidance are believed to undergo a crumpling transition when the microscopic bending stiffness is comparable to $kT$, the scale of thermal fluctuations. Most potential physical realizations of such membranes have a bending stiffness well in excess of experimentally achievable temperatures and are therefore unlikely ever to access the crumpling regime. We propose a mechanism to tune the onset of the crumpling transition by altering the geometry and topology of the sheet itself. We carry out extensive molecular dynamics simulations of perforate…
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…
Cellular membranes are elastic lipid bilayers that contain a variety of proteins, including ion channels, receptors, and scaffolding proteins. These proteins are known to diffuse in the plane of the membrane and to influence the bending of the membrane. Experiments have shown that lipid flow in the plane of the membrane is closely coupled with the diffusion of proteins. Thus, there is a need for a comprehensive framework that accounts for the interplay between these processes. Here, we present a theory for the coupled in-plane viscous flow of lipids, diffusion of transmembrane proteins, and el…
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…
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）
Manipulating the shape of nanoscale objects in a controllable fashion is at the heart of designing materials that act as building blocks for self-assembly or serve as targeted drug delivery carriers. Inducing shape deformations by controlling external parameters is also an important way of designing biomimetic membranes. In this paper, we demonstrate that electrostatics can be used as a tool to manipulate the shape of soft, closed membranes by tuning environmental conditions such as the electrolyte concentration in the medium. Using a molecular dynamics-based simulated annealing procedure, we …
The conformational free energy landscape of a system is a fundamental thermodynamic quantity of importance particularly in the study of soft matter and biological systems, in which the entropic contributions play a dominant role. While computational methods to delineate the free energy landscape are routinely used to analyze the relative stability of conformational states, to determine phase boundaries, and to compute ligand-receptor binding energies its use in problems involving the cell membrane is limited. Here, we present an overview of four different free energy methods to study morpholog…
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…
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。
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…
