La membrane cellulaire est un objet jouant divers rôles en biologie. Elle sert en particulier de barrière sélective entre l'intérieur et l'extérieur d'une cellule. Une membrane est une bicouche majoritairement composée de lipides, particulièrement de phospholipides, entre lesquels des protéines peuvent s'insérer. Les membranes ont besoin de contrôler l'organisation des protéines pour répondre à différentes fonctions biologiques. En physique de la matière condensée une interface signifie généralement une frontière entre deux phases distinctes, les fluctuations de cette frontière pouvant être étudiées avec les outils de la physique statistique et ceux associés aux phénomènes critiques. C'est dans ce cadre que s'insèrent nos travaux. Dans une première partie, nous nous sommes intéressés à l'organisation bidimensionnelle des lipides dans la membrane. Nous avons développé un modèle analytique de vésicule, objet tridimensionnel constitué d'une membrane fermée, où les lipides sont modélisés comme un fluide binaire en proportions différentes dans les deux feuillets de la bicouche. Un hamiltonien de Landau, qui décrit les interactions entre les lipides dans un feuillet, est couplé à un hamiltonien d'Helfrich qui rend compte des propriétés élastiques du système via une courbure spontanée et un module de courbure élastique qui dépendent de la composition locale. Dans ce modèle, le système présente différentes phases thermodynamiques qui peuvent être associées à des domaines soit épais soit courbés. Les domaines épais sont de bons candidats pour modéliser les radeaux (ou "rafts") lipidiques, qui jouent supposément le rôle de plate-forme de signalisation pour les cellules. La seconde partie porte sur l'impact de ces différentes phases sur la forme globale des vésicules. Pour répondre à cette question nous avons développé un programme numérique qui simule des vésicules composées de différents lipides. Lors de la comparaison de nos premiers résultats avec les solutions du modèle analytique, nous nous sommes aperçus qu'il existe une différence importante entre les paramètres élastiques microscopiques et ceux associés aux spectres de fluctuations mesurés. En effet, deux paramètres sufisent pour décrire le modèle de Helfrich, la tension de surface et le module de courbure élastique. Bien que les variations du module de courbure soient faibles, celles de la tension de surface sont importantes. Nous avons obtenus une formule simple qui relie la tension microscopique à celle du spectre des fluctuations. A l'aide de simulations Monte Carlo extensives et précises nous avons vérifié l'accord de ces résultats. De plus, nous avons étudié la transition de la forme sphérique à la forme "érythrocyte" et montré qu'elle pouvait être associée à l'annulation de la tension de Laplace du système. Nous avons également re-exploré la renormalisation des paramètres du modèle d'Helfrich pour une membrane plane et fait une analogie avec le modèle delta non- linéaire, un modèle de spins bien connu en matière condensée. / The cell membrane is an object playing many roles in biology. It is used in particular as a selective barrier between the interior and the exterior of a cell. A membrane is a bilayer composed mostly of lipids, and in particular of phospholipids, in which proteins can be inserted. The membrane needs to control the spatial organization of proteins to achieve various biological functions. In condensed matter physics, an interface usually means a boundary between two phases, the fluctuations of such border can be studied with the tools of statistical physics and those of critical phenomena. It is in this context that our work is inscribed. In a first part, we are interested in the two-dimensional organization of lipids in the membrane. We have developed an analytical model of a vesicle, a three-dimensional object consisting of a closed membrane, where the lipid bilayer is modeled as a binary mixture with di erent average compositions on both leaflets. A Landau hamiltonian describing the lipid- lipid interactions on each leaflet is coupled to a Helfrich one, accounting for the membrane elasticity, via both a local spontaneous curvature, and a bending modulus which depend on the local composition of lipids. In this model there are different thermodynamics phases that can be associated with thick or curved patches. These thick patches are good candidates for modeling lipidic rafts, which serve as signaling platforms for cells. The second issue concerns the impact of the different phases on the global shape of the vesicles. To answer this, we developed a numerical code that simulates vesicles composed of various lipids. When we compared our first results with analytical solutions, we realized that there is a significant difference between the microscopic elastic parameters and those associated with the fluctuation spectrum in the output of the simulation. Indeed, two parameters are enough to describe the Helfrich hamiltonian, the surface tension and the bending modulus. Although we observe small changes in the bending modulus, those of the surface tension are important. We have obtained a simple formula which connects the microscopic tension with the one associated with the fluctuation spectrum. Using extensive and accurate Monte Carlo simulations we checked the agreement of these results. In addition, we have studied the transition from the spherical shape to the "erythrocyte" one and showed that it could be associated with the cancellation of the Laplace pressure. We also explored the renormalization of Helfrich parameters for a flat membrane and proposed an analogy with the nonlinear delta model, a well known spin model in condensed matter.

The interaction of nanoparticles with biological systems, especially interactions with cell membranes, has been a subject of active research due to its numerous applications in many areas of soft-matter and biological systems. Within only a few relevant physical parameters profound structural properties have been discovered in the context of simple coarse-grained theoretical models. In this Thesis we study the structure of a tubular membrane adhering to two rigid cylindrical particles on a basis of a free-energy model that uses Helfrich energy for the description of the membrane. A numerical procedure is developed to solve the shape equations that determine the state of lowest energy. Several phase transitions exist in the system, arising from the competition between the bending energy of the membrane and the adhesion energy between the membrane and the particles. A continuous adhesion transition between the free and bound states, as well as several discontinuous shape transitions are identified, depending on the physical parameters of the system. The results are then generalized into a single phase diagram separating free, symmetric- and asymmetric-wrapping states in the phase space of the size of the particles and the adhesion energy. We show that for a relatively small size of the membrane tube the interaction between the cylinders becomes attractive in the strong curvature regime, leading to aggregation of the particles in the highly curved area of the tube that is characteristically different from the aggregation in a related three-dimensional system. For a relatively large membrane tube size the cylinders prefer to have a non-zero separation, even in the completely engulfed state. This indicates that, i) the spontaneous curvature of the membrane may play a role in the sign of the interaction of two colloidal particles adhered to a membrane and ii) cylindrical particles can aggregate on membrane tubes and vesicles if the curvature of the membrane around the aggregation region is sufficiently large.

The interaction of nanoparticles with biological systems, especially interactions with cell membranes, has been a subject of active research due to its numerous applications in many areas of soft-matter and biological systems. Within only a few relevant physical parameters profound structural properties have been discovered in the context of simple coarse-grained theoretical models. In this Thesis we study the structure of a tubular membrane adhering to two rigid cylindrical particles on a basis of a free-energy model that uses Helfrich energy for the description of the membrane. A numerical procedure is developed to solve the shape equations that determine the state of lowest energy. Several phase transitions exist in the system, arising from the competition between the bending energy of the membrane and the adhesion energy between the membrane and the particles. A continuous adhesion transition between the free and bound states, as well as several discontinuous shape transitions are identified, depending on the physical parameters of the system. The results are then generalized into a single phase diagram separating free, symmetric- and asymmetric-wrapping states in the phase space of the size of the particles and the adhesion energy. We show that for a relatively small size of the membrane tube the interaction between the cylinders becomes attractive in the strong curvature regime, leading to aggregation of the particles in the highly curved area of the tube that is characteristically different from the aggregation in a related three-dimensional system. For a relatively large membrane tube size the cylinders prefer to have a non-zero separation, even in the completely engulfed state. This indicates that, i) the spontaneous curvature of the membrane may play a role in the sign of the interaction of two colloidal particles adhered to a membrane and ii) cylindrical particles can aggregate on membrane tubes and vesicles if the curvature of the membrane around the aggregation region is sufficiently large.

En biologie, lorsqu'une quantité importante de phospholipides est insérée dans un milieu aqueux, ceux-Ci s'assemblent alors par paires pour former une bicouche, plus communément appelée vésicule. En 1973, Helfrich a proposé un modèle simple pour décrire la forme prise par une vésicule. Imposant la surface de la bicouche et le volume de fluide qu'elle contient, leur forme minimise une énergie élastique faisant intervenir des quantités géométriques comme la courbure, ainsi qu'une courbure spontanée mesurant l'asymétrie entre les deux couches. Les globules rouges sont des exemples de vésicules sur lesquels sont fixés un réseau de protéines jouant le rôle de squelette au sein de la membrane. Un des principaux travaux de la thèse fut d'introduire et étudier une condition de boule uniforme, notamment pour modéliser l'effet du squelette. Dans un premier temps, on cherche à minimiser l'énergie de Helfrich sans contrainte puis sous contrainte d'aire. Le cas d'une courbure spontanée nulle est connu sous le nom d'énergie de Willmore. Comme la sphère est un minimiseur global de l'énergie de Willmore, c'est un bon candidat pour être un minimiseur de l'énergie de Helfrich parmi les surfaces d'aire fixée. Notre première contribution dans cette thèse a été d'étudier son optimalité. On montre qu'en dehors d'un certain intervalle de paramètres, la sphère n'est plus un minimum global, ni même un minimum local. Par contre, elle est toujours un point critique. Ensuite, dans le cas de membranes à courbure spontanée négative, on se demande si la minimisation de l'énergie de Helfrich sous contrainte d'aire peut être effectuée en minimisant individuellement chaque terme. Cela nous conduit à minimiser la courbure moyenne totale sous contrainte d'aire et à déterminer si la sphère est la solution de ce problème. On montre que c'est le cas dans la classe des surfaces axisymétriques axiconvexes mais que ce n'est pas vrai en général.Enfin, lorsqu'une contrainte d'aire et de volume sont considérées simultanément, le minimiseur ne peut pas être une sphère qui n'est alors plus admissible. En utilisant le point de vue de l'optimisation de formes, la troisième et plus importante contribution de cette thèse est d'introduire une classe plus raisonnable de surfaces, pour laquelle l'existence d'un minimiseur suffisamment régulier est assurée pour des fonctionnelles et des contraintes générales faisant intervenir les propriétés d'ordre un et deux des surfaces. En s'inspirant de ce que fit Chenais en 1975 quand elle a considéré la propriété de cône uniforme, on considère les surfaces satisfaisant une condition de boule uniforme. On étudie d'abord des fonctionnelles purement géométriques puis nous autorisons la dépendance à travers la solution de problèmes aux limites elliptiques d'ordre deux posés sur le domaine intérieur à la surface / In biology, when a large amount of phospholipids is inserted in aqueous media, they immediatly gather in pairs to form bilayers also called vesicles. In 1973, Helfrich suggested a simple model to characterize the shapes of vesicles. Imposing the area of the bilayer and the volume of fluid it contains, their shape is minimizing a free-Bending energy involving geometric quantities like curvature, and also a spontanuous curvature measuring the asymmetry between the two layers. Red blood cells are typical examples of vesicles on which is fixed a network of proteins playing the role of a skeleton inside the membrane. One of the main work of this thesis is to introduce and study a uniform ball condition, in particular to model the effects of the skeleton. First, we minimize the Helfrich energy without constraint then with an area constraint. The case of zero spontaneous curvature is known as the Willmore energy. Since the sphere is the global minimizer of the Willmore energy, it is a good candidate to be a minimizer of the Helfrich energy among surfaces of prescribed area. Our first main contribution in this thesis was to study its optimality. We show that apart from a specific interval of parameters, the sphere is no more a global minimizer, neither a local minimizer. However, it is always a critical point. Then, in the specific case of membranes with negative spontaneous curvature, one can wonder whether the minimization of the Helfrich energy with an area constraint can be done by minimizing individually each term. This leads us to minimize total mean curvature with prescribed area and to determine if the sphere is a solution to this problem. We show that it is the case in the class of axisymmetric axiconvex surfaces but that it does not hold true in the general case. Finally, considering both area and volume constraints, the minimizer cannot be the sphere, which is no more admissible. Using the shape optimization point of view, the third main and most important contribution of this thesis is to introduce a more reasonable class of surfaces, in which the existence of an enough regular minimizer is ensured for general functionals and constraints involving the first- and second-Order geometric properties of surfaces. Inspired by what Chenais did in 1975 when she considered the uniform cone property, we consider surfaces satisfying a uniform ball condition. We first study purely geometric functionals then we allow a dependence through the solution of some second-Order elliptic boundary value problems posed on the inner domain enclosed by the shape

A simulação computacional de membranas biológicas, em particular membranas formadas por bicamadas lipídicas, é uma área de grande interesse na atualidade. Enquanto simulações moleculares são bastante populares, a simulação na escala de uma célula inteira requer modelos baseados na mecânica dos meios contínuos. Essas membranas apresentam um comportamento de fluido viscoso incompressível bidimensional. Além disso, as formas de equilíbrio são bem explicadas pela energia de Canham-Helfrich, que depende da curvatura da membrana. Neste trabalho, um novo método de simulação de membranas viscosas, baseado em elementos finitos, é apresentado. Ele se inspira no conceito de James Clerk Maxwell de elasticidade fugaz, o qual é usado para adaptar técnicas bem estabelecidas de simulação de membranas elásticas. Trata-se do primeiro método a levar em conta, de maneira rigorosa, o aspecto viscoso da membrana, que é dominante na escala de tamanho de uma célula biológica, além da sua característica de fluido incompressível / The computational simulation of biological membranes, in particular of those made of lipid bilayers, is currently an area of great interest. While molecular simulations are quite popular, the simulation on the scale of a whole cell requires models based on continuum mechanics. Those membranes behave like a bidimensional incompressible viscous fluid. Furthermore, the equilibrium shapes are well explained by means of the Canham-Helfrich energy, which depends on the curvature of the membrane. In this work, a novel finite element based method for the simulation of viscous membranes is presented. It is inspired by James Clerk Maxwells concept of fugitive elasticity, which is used to adapt well established simulation techniques for elastic membranes. This is the first method to take into account, in a rigorous fashion, the viscous aspect of the membrane, which is dominant at the length scale of a biological cell, in addition to its characteristics as an incompressible fluid

A simulação computacional de membranas biológicas, em particular membranas formadas por bicamadas lipídicas, é uma área de grande interesse na atualidade. Enquanto simulações moleculares são bastante populares, a simulação na escala de uma célula inteira requer modelos baseados na mecânica dos meios contínuos. Essas membranas apresentam um comportamento de fluido viscoso incompressível bidimensional. Além disso, as formas de equilíbrio são bem explicadas pela energia de Canham-Helfrich, que depende da curvatura da membrana. Neste trabalho, um novo método de simulação de membranas viscosas, baseado em elementos finitos, é apresentado. Ele se inspira no conceito de James Clerk Maxwell de elasticidade fugaz, o qual é usado para adaptar técnicas bem estabelecidas de simulação de membranas elásticas. Trata-se do primeiro método a levar em conta, de maneira rigorosa, o aspecto viscoso da membrana, que é dominante na escala de tamanho de uma célula biológica, além da sua característica de fluido incompressível / The computational simulation of biological membranes, in particular of those made of lipid bilayers, is currently an area of great interest. While molecular simulations are quite popular, the simulation on the scale of a whole cell requires models based on continuum mechanics. Those membranes behave like a bidimensional incompressible viscous fluid. Furthermore, the equilibrium shapes are well explained by means of the Canham-Helfrich energy, which depends on the curvature of the membrane. In this work, a novel finite element based method for the simulation of viscous membranes is presented. It is inspired by James Clerk Maxwells concept of fugitive elasticity, which is used to adapt well established simulation techniques for elastic membranes. This is the first method to take into account, in a rigorous fashion, the viscous aspect of the membrane, which is dominant at the length scale of a biological cell, in addition to its characteristics as an incompressible fluid

Ce travail, à l'interface entre les mathématiques appliquées et la physique, s'articule autour de la modélisation numérique des vésicules biologiques, un modéle pour les globules rouges du sang. Pour cela, le modéle de Canham et Helfrich est adopté pour décrire le comportement des vésicules. La modélisation numérique utilise la méthode des fonctions de niveau dans un cadre éléments finis. Un nouvel algorithme de résolution numérique combinant une technique de multiplicateurs de Lagrange avec une adaptation automatique de maillages garantit la conservation exacte des volumes et des surfaces. Cet algorithme permet donc de dépasser une limitation cruciale actuelle de la méthode des fonctions de niveau, à savoir les pertes de masse couramment observées dans ce type de problémes. De plus, les propriétés de convergence de la méthode des fonctions de niveau se trouvent ainsi grandement améliorées, comme l'indiquent de nombreux tests numériques. Ces tests comprennent notamment des problémes d'advection élémentaires, des mouvements par courbure moyenne ainsi que des mouvements par diffusion de surface. Concernant l'équilibre statique des vésicules, une condition générale d'équilibre d'Euler-Lagrange est obtenue à l'aide d'outils de dérivation de forme. En dynamique, le mouvement d'une vésicule sous l'action d'un écoulement de cisaillement est étudié dans le cadre des nombres de Reynolds élevés. L'effet du confinement est considéré, et les régimes classiques de chenille de char et de basculement sont retrouvés. Finalement, pour la premiére fois, l'effet des termes inertiels est étudié et on montre qu'au delà d'une valeur critique du nombre de Reynolds, la vésicule passe d'un mouvement de basculement à un mouvement de chenille de char. / This work, at the interface between the Applied Mathematics and Physics is connected about the numerical modelisation of biological vesicles, a pattern for the red blood cells. For this reason, the pattern of Canham and Helfrich is adopted to describe the behaviour of the vesicles. The numerical modelisation uses the Level Set method in finite element framework. A new algorithm of numerical resolution combining one technique of Lagrange multipliers with an automatic mesh adaptation ensures the accurate conservation of volumes and surfaces. Thus this algorithm enables to exceed an existing crucial restriction of the Level Set method, that's to say, the wastes of mass usually noticed in this kind of problems. Moreover, the proprieties of convergence of the Level Set method are thus much more improved, as shown in many numerical tests. Those tests chiefly include elementary problems of advection, motions by mean curvature just as motions by spread of surface. Concerning the static equilibrum of the vesicles, a mechanical equilibrum equation (Euler-Lagrange equation) of a vesicle membrane under a generalized elastic bending energy is obtained and the approach is based on shape optimization tools. In dynamics, the motion of a vesicle under the effect of a shear flow is elaborated in the frames of reference of high Reynolds numbers. The effect of confinement is respected, and the standard regimes of tank-treading and of tumbling motion are found again. Finally, for the first time, the effect of the inertia terms is elaborated and we show that beyond a critical value of the number of Reynolds the vesicle passes from a tumbling motion to a tank-treading motion.

<p>The bending moduli and line tension of bilayer membranes self-assembled from diblock copolymers was calculated using the self-consistent field theory. The limitation of the linear elasticity theory (Helfrich model) was evaluated by calculating fourth- order curvature moduli in high curvature systems. It was found that in highly curved membranes, the fourth-order contributions to the bending energy becomes comparable to the low-order terms. The line tension (γL) of membrane pores was also investigated for mixtures of structurally different diblock copolymers. The line ten- sion was found to depend sensitively on the diblock chain topology. Addition of short hydrophobic copolymers was found to reduce the line tensions to negative values, showing that lipid mixtures may be used as pore stabilizers.</p> / Master of Science (MSc)

Ce travail, à l'interface entre les mathématiques appliquées et la physique, s'articule autour de la modélisation numérique des vésicules biologiques, un modéle pour les globules rouges du sang. Pour cela, le modéle de Canham et Helfrich est adopté pour décrire le comportement des vésicules. La modélisation numérique utilise la méthode des fonctions de niveau dans un cadre éléments finis. Un nouvel algorithme de résolution numérique combinant une technique de multiplicateurs de Lagrange avec une adaptation automatique de maillages garantit la conservation exacte des volumes et des surfaces. Cet algorithme permet donc de dépasser une limitation cruciale actuelle de la méthode des fonctions de niveau, à savoir les pertes de masse couramment observées dans ce type de problémes. De plus, les propriétés de convergence de la méthode des fonctions de niveau se trouvent ainsi grandement améliorées, comme l'indiquent de nombreux tests numériques. Ces tests comprennent notamment des problémes d'advection élémentaires, des mouvements par courbure moyenne ainsi que des mouvements par diffusion de surface. Concernant l'équilibre statique des vésicules, une condition générale d'équilibre d'Euler-Lagrange est obtenue à l'aide d'outils de dérivation de forme. En dynamique, le mouvement d'une vésicule sous l'action d'un écoulement de cisaillement est étudié dans le cadre des nombres de Reynolds élevés. L'effet du confinement est considéré, et les régimes classiques de chenille de char et de basculement sont retrouvés. Finalement, pour la premiére fois, l'effet des termes inertiels est étudié et on montre qu'au delà d'une valeur critique du nombre de Reynolds, la vésicule passe d'un mouvement de basculement à un mouvement de chenille de char.

Because cells are machines, their structure determines their function (health). But their structure also determines cells’ mechanical properties. So if we can understand how cells’ mechanical properties are influenced by specific structures, then we can observe what’s happening inside of cells via mechanical measurements. The Atomic Force Microscope (AFM) has become a standard tool for investigating the mechanical properties of cells. In many experiments, an AFM is used to ‘poke’ adherent cells with nanonewton forces, and the resulting deformation observed via, e.g. Laser Scanning Confocal Microscopy. Results of such experiments are often interpreted in terms of continuum mechanical models which characterize the cell as a linear viscoelastic solid. This “top-down” approach of poking an intact cell —complete with cytoskeleton, organelles etc.— can be problematic when trying to measure the mechanical properties and response of a single cell component. Moreover, how are we to know the sensitivity of the cell’s mechanical properties to partial modification of a single component (e.g. reducing the degree of cross- linking in the actin cortex)? In contrast, the approach taken here —studying the deformation and relaxation of lipid bilayer vesicles— might be called a “bottom-up” approach to cell mechanics. Using Coarse- Grained Molecular Dynamics simulations, we study the deformation and relaxation of bilayer vesicles, when poked with constant force. The relaxation time, equilibrium area expansion, and surface tension of the vesicle membrane are studied over a range of applied forces. Interestingly, the relaxation time exhibits a strong force-dependence. Force-compression curves for our simulated vesicle show a strong similarity to recent experiments where giant unilamellar vesicles were compressed in a manner nearly identical to that of our simulations.