We systematize and extend the description of vesicle growth and shape change using linear nonequilibrium thermodynamics. By restricting the study to shape changes from spheres to axisymmetric ellipsoids, we are able to give a consistent formulation which includes the lateral tension of the vesicle membrane. This allows us to generalize and correct a previous calculation. Our present calculations suggest that, for small growing vesicles, a prolate ellipsoidal shape should be favored over oblate ellipsoids, whereas for large growing vesicles oblates should be favored over prolates. The validity of this prediction is examined in the light of the various assumptions made in its derivation.
A mechanism is proposed for the growth of vesicles dispersed in a liquid solvent and a size distribution function is obtained for the vesicles, both from the first principles calculations. This distribution function is shown to be positively skewed and evolving in time obeying a Fokker-Planck type equation. The critical size of the spherical vesicles is shown to grow in time with an exponent of 0.25. A constant is suggested that characterizes how easily a vesicle can absorb amphiphiles into its periphery.
Using a microfluidic trap, we study the behavior of individual phospholipid vesicles in contact with fatty acids. We show that spontaneous fatty acids insertion inside the bilayer is controlled by the vesicle size, osmotic pressure difference across the membrane and fatty acids concentration in the external bath. Depending on these parameters, vesicles can grow spherically or become unstable and fragment into several daughter vesicles. We establish the phase diagram for vesicle growth and we derive a simple thermodynamic model that reproduces the time evolution of the vesicle volume. Finally, …
Morphologies of genus-1 and 2 toroidal vesicles are studied numerically by dynamically triangulated membrane models and experimentally by confocal laser microscopy. Our simulation results reproduce shape transformations observed in our experiments well. At large reduced volumes of the genus-1 vesicles, obtained vesicle shapes agree with the previous theoretical prediction, in which axisymmetric shapes are assumed: double-necked stomatocyte, discoidal toroid, and circular toroid. However, for small reduced volumes, it is revealed that a non-axisymmetric discoidal toroid and handled discocyte ex…
Motivated by recent experiments on multi-component membranes, the growth kinetics of domains on vesicles is theoretically studied. It is known that the steady-state rate of coalescence cannot be obtained by taking the long-time limit of the coalescence rate when the membrane is regarded as an infinite two-dimensional (2D) system. The steady-state rate of coalescence is obtained by explicitly taking into account the spherical vesicle shape. Using the expression of the 2D diffusion coefficient obtained in the limit of small domain size, an analytical expression for the domain growth kinetics is …
The shape transformations of fluid membranes induced by curved protein rods are studied using meshless membrane simulations. The rod assembly at low rod density induces a flat membrane tube and oblate vesicle. It is found that the polyhedral shapes are stabilized at high rod densities. The discrete shape transition between triangular and buckled discoidal tubes is obtained and their curvature energies are analyzed by a simple geometric model. For vesicles, triangular hosohedron and elliptic-disk shapes are formed in equilibrium, whereas tetrahedral and triangular prism shapes are obtained as m…
The morphologies of genus-2 to -8 fluid vesicles are studied by using dynamically triangulated membrane simulations with area-difference elasticity. It is revealed that the alignments of the membrane pores alter the vesicle shapes and the types of shape transitions for the genus $g \ge 3$. At a high reduced volume, a stomatocyte with a circular alignment of $g+1$ pores continuously transforms into a discocyte with a line of $g$ pores with increasing intrinsic area difference. In contrast, at a low volume, a stomatocyte transforms into a ($g+1$)-hedral shape and subsequently exhibits a discrete…
Morphologies of a vesicle confined in a spherical vesicle were explored experimentally by fast confocal laser microscopy and numerically by a dynamically-triangulated membrane model with area-difference elasticity. The confinement was found to induce several novel shapes of the inner vesicles, that had been never observed in unilamellar vesicles: double and quadruple stomatocytes, slit vesicle, and vesicles of two or three compartments with various shapes. The simulations reproduced the experimental results very well and some of the shape transitions can be understood by a simple theoretical m…
We describe the growth of vesicles, due to the accretion of lipid molecules to their surface, in terms of linear irreversible thermodynamics. Our treatment differs from those previously put forward by consistently including the energy of the membrane in the thermodynamic description. We calculate the critical radius at which the spherical vesicle becomes unstable to a change of shape in terms of the parameters of the model. The analysis is carried out both for the case when the increase in volume is due to the absorption of water and when a solute is also absorbed through the walls of the vesi…
While the behavior of vesicles in thermodynamic equilibrium has been studied extensively, how active forces control vesicle shape transformations is not understood. Here, we combine theory and simulations to study the shape behavior of vesicles containing active Brownian particles. We show that the combination of active forces, dimensionality and membrane bending free energy creates a plethora of novel phase transitions. At low swim pressure, the vesicle exhibits a discontinuous transition from a spherical to a prolate shape, which has no counterpart in two dimensions. At high swim pressure it…
Cellular membranes exhibit a large variety of shapes, strongly coupled to their function. Many biological processes involve dynamic reshaping of membranes, usually mediated by proteins. This interaction works both ways: while proteins influence the membrane shape, the membrane shape affects the interactions between the proteins. To study these membrane-mediated interactions on closed and anisotropically curved membranes, we use colloids adhered to ellipsoidal membrane vesicles as a model system. We find that two particles on a closed system always attract each other, and tend to align with the…
The growth, form, and division of prebiotic vesicles, membraneous bags of fluid of varying components and shapes is hypothesized to have served as the substrate for the origin of life. The dynamics of these out-of-equilibrium structures is controlled by physicochemical processes that include the intercalation of amphiphiles into the membrane, fluid flow across the membrane, and elastic deformations of the membrane. To understand prebiotic vesicular forms and their dynamics, we construct a minimal model that couples membrane growth, deformation, and fluid permeation, ultimately couched in terms…
The shape equation and linking conditions for a vesicle with two-phase domains are derived. We refine the conjecture on the general neck condition for the limit shape of a budding vesicle proposed by Jülicher and Lipowsky [Phys. Rev. Lett. \textbf{70}, 2964 (1993); Phys. Rev. E \textbf{53}, 2670 (1996)], and then we use the shape equation and linking conditions to prove that this conjecture holds not only for axisymmetric budding vesicles, but also for asymmetric ones. Our study reveals that the mean curvature at any point on the membrane segments adjacent to the neck satisfies the general nec…
We present a numerical study of the time-dependent motion of a two-dimensional vesicle in a channel under an imposed flow. In a Poiseuille flow the shape of the vesicle depends on the flow strength, the mechanical properties of the membrane, and the width of the channel as reported in the past. This study is focused on the centered snaking (CSn) shape, where the vesicle shows an oscillatory motion like a swimmer flagella even though the flow is stationary. We quantify this behavior by the amplitude and frequency of the oscillations of the vesicle's center of mass. We observe regions in paramet…
Using field theoretic approach, we study equilibrium shape deformation of a vesicle induced by the presence of enclosed flexible polymers, which is a simple model of drug delivery system or endocytosis. To evaluate the total free energy of this system, it is necessary to calculate the bending elastic energy of the membrane, the conformation entropy of the polymers and their interactions. For this purpose, we combine phase field theory for the membrane and self-consistent field theory for the polymers. Simulations on this coupled model system for axiosymmetric shapes show a shape deformation of…
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 dynamics of fluid vesicles is studied under flow in microchannels, in which the width varies periodically along the channel. Three types of flow instabilities of prolate vesicles are found. For small quasi-spherical vesicles -- compared to the average channel width -- perturbation theory predicts a transition from a state with orientational oscillations of a fixed prolate shape to a state with shape oscillations of symmetrical ellipsoidal or bullet-like shapes with increasing flow velocity. Experimentally, such orientational oscillations are observed during the slow migration of a vesicle …
One of the most widely used methods for determination of the bending elasticity modulus of model lipid membranes is the analysis of the shape fluctuations of nearly spherical lipid vesicles. The theoretical basis of this analysis is given by Milner and Safran. In their theory the stretching effects are not considered. In the present study we generalized their approach including the stretching effects deduced after an application of statistical mechanics of vesicles.
Non-uniform fields are commonly used to study vesicle dielectrophoresis and can be used to hitherto relatively unexplored areas of vesicle deformation and electroporation. A common but perplexing problem in vesicle dynamics is the cross over from the entropic to enthalpic (stretching) tension during vesicle deformation. A lucid demonstration of this concept is provided by the study of vesicle deformation and dielectrophoresis under axisymmetric quadrupole electric field. Small deformation theory incorporating the Maxwell stress approach is used (employing area and volume conservation constrain…
We analyse the effects that the impermeability constraint induces on the equilibrium shapes of a three-dimensional vesicle hosting a rigid inclusion. A given alteration of the inclusion and/or vesicle parameters leads to shape modifications of different orders of magnitude, when applied to permeable or impermeable vesicles. Moreover, the enclosed-volume constraint wrecks the uniqueness of stationary equilibrium shapes, and gives rise to pear-shaped or stomatocyte-like vesicles.
The dynamics of phase separation in multi-component bilayer fluid vesicles is investigated by means of large-scale dissipative particle dynamics. The model explicitly accounts for solvent particles, thereby allowing for the very first numerical investigation of the effects of hydrodynamics and area-to-volume constraints. We observed regimes corresponding to coalescence of flat patches, budding and vesiculation, and coalescence of caps. We point out that the area-to-volume constraint has a strong influence on crossovers between these regimes.
We develop coarse-grained particle approaches for studying the elastic mechanics of vesicles with heterogeneous membranes having phase-separated domains. We perform simulations both of passive shape fluctuations and of active systems where vesicles are subjected to compression between two plates or subjected to insertion into narrow channels. Analysis methods are developed for mapping particle configurations to continuum fields with spherical harmonics representations. Heterogeneous vesicles are found to exhibit rich behaviors where the heterogeneity can amplify surface two-point correlations,…
We investigate numerically the dynamics of shape and displacement fluctuations of two-dimensional flexible vesicles filled with active particles. At low concentration most of the active particles accumulate at the boundary of the vesicle where positive particle number fluctuations are amplified by trapping, leading to the formation of pinched spots of high density, curvature and pressure. At high concentration the active particles cover the vesicle boundary almost uniformly, resulting in fairly homogeneous pressure and curvature, and nearly circular vesicle shape. The change between polarized …
Phase-contrast microscopy is used to monitor the shapes of micron-scale fluid-phase phospholipid-bilayer vesicles in aqueous solution. At fixed temperature, each vesicle undergoes thermal shape fluctuations. We are able experimentally to characterize the thermal shape ensemble by digitizing the vesicle outline in real time and storing the time-sequence of images. Analysis of this ensemble using the area-difference-elasticity (ADE) model of vesicle shapes allows us to associate (map) each time-sequence to a point in the zero-temperature (shape) phase diagram. Changing the laboratory temperature…
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…
Renormalized mechanics and stochastic thermodynamics of growing vesicles
The James Franck Institute, University of Chicago（芝加哥大学詹姆斯·弗兰克研究所）；Department of Chemistry, University of Chicago（芝加哥大学化学系）；Engineering Sciences and Applied Mathematics, Northwestern University（西北大学工程科学与应用数学系）
Eukaryote cells have a flexible shape, which dynamically changes according to the function performed by the cell. One mechanism for deforming the cell membrane into the desired shape is through the expression of curved membrane proteins. Furthermore, these curved membrane proteins are often associated with the recruitment of the cytoskeleton, which then applies active forces that deform the membrane. This coupling between curvature and activity was previously explored theoretically in the linear limit of small deformations, and low dimensionality. Here we explore the unrestricted shapes of ves…
Lipid vesicles play a key role in fundamental biological processes. Despite recent progress, we lack a complete understanding of the non-equilibrium dynamics of vesicles due to challenges associated with long-time observation of shape fluctuations in strong flows. In this work, we present a flow-phase diagram for vesicle shape and conformational transitions in planar extensional flow using a Stokes trap, which enables control over the center-of-mass position of single or multiple vesicles in precisely defined flows [Shenoy, Rao, Schroeder, \textit{PNAS}, 113(15):3976-3981, 2016]. In this way, …
Soft bodies flowing in a channel often exhibit parachute-like shapes usually attributed to an increase of hydrodynamic constraint (viscous stress and/or confinement). We show that the presence of a fluid membrane leads to the reverse phenomenon and build a phase diagram of shapes --- which are classified as bullet, croissant and parachute --- in channels of varying aspect ratio. Unexpectedly, shapes are relatively wider in the narrowest direction of the channel. We highlight the role of flow patterns on the membrane in this response to the asymmetry of stress distribution.
A photosensitive amphiphilic molecule can switch the shape of an assembled vesicle as determined by microscopic observation. Photo-isomerization induces a change in membrane fluctuation behavior or a morphological transition between ellipsoid and bud shapes, depending on the asymmetrical degree of the initial shape. The mechanism of this reversible photo-switching in the vesicle morphology is interpreted in terms of a change in the effective cross-sectional area of the photosensitive molecule.
Despite the recent upsurge of theoretical reduced models for vesicle shape dynamics, comparisons with experiments have not been accomplished. We review the implications of some of the recently proposed models for vesicle dynamics, especially the Tumbling-Trembling domain regions of the phase plane and show that they all fail to capture the essential behavior of real vesicles for excess areas, Δ, greater than 0.4. We emphasize new observations of shape harmonics and the role of thermal fluctuations.
The general Helfrich shape equation determined by minimizing the curvature free energy describes the equilibrium shapes of the axisymmetric lipid bilayer vesicles in different conditions. It is a non-linear differential equation with variable coefficients. In this letter, by analyzing the unique property of the solution, we change this shape equation into a system of the two differential equations. One of them is a linear differential equation. This equation system contains all of the known rigorous solutions of the general shape equation. And the more general constraint conditions are found f…
The steady motion and deformation of a lipid-bilayer vesicle translating through a circular tube in low Reynolds number pressure-driven flow are investigated numerically using an axisymmetric boundary element method. This fluid-structure interaction problem is determined by three dimensionless parameters: reduced volume (a measure of the vesicle asphericity), geometric confinement (the ratio of the vesicle effective radius to the tube radius), and capillary number (the ratio of viscous to bending forces). The physical constraints of a vesicle -- fixed surface area and enclosed volume when it i…
We show that the stacking of flat aromatic molecules on a curved surface results in topological defects. We consider, as an example, spherical vesicles, self-assembled from molecules with 5- and 6-thiophene cores. We predict that the symmetry of the molecules influences the number of topological defects and the resulting equilibrium shape.
Can the presence of molecular-tilt order significantly affect the shapes of lipid bilayer membranes, particularly membrane shapes with narrow necks? Motivated by the propensity for tilt order and the common occurrence of narrow necks in the intermediate stages of biological processes such as endocytosis and vesicle trafficking, we examine how tilt order inhibits the formation of necks in the equilibrium shapes of vesicles. For vesicles with a spherical topology, point defects in the molecular order with a total strength of $+2$ are required. We study axisymmetric shapes and suppose that there …
Lipid vesicles are known to undergo complex conformational transitions, but it remains challenging to systematically characterize non-equilibrium membrane shape dynamics. Here, we report the direct observation of lipid vesicle relaxation from highly deformed shapes using a Stokes trap. Vesicle shape relaxation is described by two distinct characteristic time scales governed by the bending modulus and membrane tension. Interestingly, experimental results are consistent with a viscoelastic model of a deformed membrane. Overall, these results show that vesicle relaxation is governed by an interpl…
We investigate the morphology of a toroidal fluid membrane vesicle confined inside a spherical container. The equilibrium shapes are assembled in a geometrical phase diagram as a function of scaled area and reduced volume of the membrane. For small area the vesicle can adopt its free form. When increasing the area, the membrane cannot avoid contact and touches the confining sphere along a circular contact line, which extends to a zone of contact for higher area. The elastic energies of the equilibrium shapes are compared to those of their confined counterparts of spherical topology to predict …
A phase-field model that takes into account the bending energy of fluid vesicles is presented. The Canham-Helfrich model is derived in the sharp-interface limit. A dynamic equation for the phase-field has been solved numerically to find stationary shapes of vesicles with different topologies and the dynamic evolution towards them. The results are in agreement with those found by minimization of the Canham-Helfrich free energy. This fact shows that our phase-field model could be applied to more complex problems of instabilities.
In this paper, the dynamics of spontaneous shape fluctuations of a single, giant quasi-spherical vesicle formed of a single lipid species is revisited theoretically. A coherent physical theory for the dynamics is developed based on a number of fundamental principles and considerations and a systematic formulation of the theory is also established. From the systematic theoretical formulation, an analytical description of the dynamics of shape fluctuations of quasi-spherical vesicles is derived. In particular, in developing the theory we have made a new interpretation of some of the phenomenolog…
Red blood cells (RBCs) are the major component of blood and the flow of blood is dictated by that of RBCs. We employ vesicles, which consist of closed bilayer membranes enclosing a fluid, as a model system to study the behavior of RBCs under a confined Poiseuille flow. We extensively explore two main parameters: i) the degree of confinement of vesicles within the channel, and ii) the flow strength. Rich and complex dynamics for vesicles are revealed ranging from steady-state shapes (in the form of parachute and slipper) to chaotic dynamics of shape. Chaos occurs through a cascade of multiple p…
Nuclear pores have an approximately uniform distribution in the nuclear envelope of most living cells. Hence, the morphology of the nuclear envelope is a spherical stomatocyte with a high genus. We have investigated the morphology of high-genus vesicles under pore-size constraint using dynamically triangulated membrane simulations. Bending-energy minimization without volume or other constraints produces a circular-cage stomatocyte, where the pores are aligned in a circular line on an oblate bud. As the pore radius is reduced, the circular-pore alignment is more stabilized than a random pore di…
We use numerical simulations to study the dynamics of three dimensional vesicles in unconfined and confined Poiseuille flow. Previous numerical studies have shown that when the fluid viscosity inside and outside the vesicle is same (no viscosity contrast), a transition from asymmetric slippers to symmetric parachutes takes place as viscous forcing or capillary number is increased. At higher viscosity contrast, an outward migration tendency has also been observed in unconfined flow simulations. In this paper, we study how the presence of viscosity contrast and confining walls affect the dynamic…
As a model of soft confinement for polymers, we investigated equilibrium shapes of a flexible vesicle that contains a phase-separating polymer solution. To simulate such a system, we combined the phase field theory (PFT) for the vesicle and the self-consistent field theory (SCFT) for the polymer solution. We observed a transition from a symmetric prolate shape of the vesicle to an asymmetric pear shape induced by the domain structure of the enclosed polymer solution. Moreover, when a non-zero spontaneous curvature of the vesicle is introduced, a re-entrant transition between the prolate and th…
Vesicles are soft elastic bodies with distinctive mechanical properties such as bending resistance, membrane fluidity, and their strong ability to deform, mimicking some properties of biological cells. While previous three-dimensional (3D) studies have identified stationary shapes such as slipper and axisymmetric ones, we report a complete phase diagram of 3D vesicle dynamics in a bounded Poiseuille flow with two more oscillatory dynamics, 3D snaking and swirling. 3D snaking is characterized by planar oscillatory motion of the mass center and shape deformations, which is unstable and leads to …
In active matter systems, deformable boundaries provide a mechanism to organize internal active stresses and perform work on the external environment. To study a minimal model of such a system, we perform particle-based simulations of an elastic vesicle containing a collection of polar active filaments. The interplay between the active stress organization due to interparticle interactions and that due to the deformability of the confinement leads to a variety of filament spatiotemporal organizations that have not been observed in bulk systems or under rigid confinement, including highly-aligne…
We explore the interplay of membrane curvature and nonspecific binding due to excluded-volume effects among colloidal particles inside lipid bilayer vesicles. We trapped submicron spheres of two different sizes inside a pear-shaped, multilamellar vesicle and found the larger spheres to be pinned to the vesicle's surface and pushed in the direction of increasing curvature. A simple model predicts that hard spheres can induce shape changes in flexible vesicles. The results demonstrate an important relationship between the shape of a vesicle or pore and the arrangement of particles within it.
We apply the Bogomol'nyi technique, which is usually invoked in the study of solitons or models with topological invariants, to the case of elastic energy of vesicles. We show that spontaneous bending contribution caused by any deformation from metastable bending shapes falls in two distinct topological sets: shapes of spherical topology and shapes of non-spherical topology experience respectively a deviatoric bending contribution a la Fischer and a mean curvature bending contribution a la Helfrich. In other words, topology may be considered to describe bending phenomena. Besides, we calculate…
Osmotically Induced Shape Changes in Membrane Vesicles
Kansas State University（堪萨斯州立大学）；NewOrbit Space Ltd（NewOrbit空间有限公司）；University of Sheffield（谢菲尔德大学）；Kaplan International College（凯伦国际学院）；Université Paris-Saclay（巴黎萨克雷大学）
Biological membranes constantly change their shape in response to external stimuli, and understanding the remodeling and stability of vesicles in heterogeneous environments is therefore of fundamental importance for a range of cellular processes. One crucial question is how vesicles respond to external osmotic stresses, imposed by differences in solute concentrations between the vesicle interior and exterior. Previous analyses of the membrane bending energy have predicted that micron-sized giant unilamellar vesicles (GUVs) should become globally deformed already for nanomolar concentration dif…
Giant unilamellar vesicles subjected to pulsed direct-current (pulsed-DC) fields are promising biomimetic systems to investigate the electroporation of cells. In strong electric fields, vesicles undergo significant deformation, which strongly alters the transmembrane potential, consequently the electroporation. Previous theoretical studies investigated the electrodeformation of vesicles in DC fields (which are not pulsed). In this work, we computationally investigate the deformation of a deflated vesicle under unipolar, bipolar, and two-step unipolar pulses and show sensitive dependence of int…
