Cell membranes are vital to shield a cell's interior from the environment. At the same time they determine to a large extent the cell's mechanical resistance to external forces. In recent years there has been considerable interest in the accurate computational modeling of such membranes, driven mainly by the amazing variety of shapes that red blood cells and model systems such as vesicles can assume in external flows. Given that the typical height of a membrane is only a few nanometers while the surface of the cell extends over many micrometers, physical modeling approaches mostly consider the interface as a two-dimensional elastic continuum. Here we review recent modeling efforts focusing on one of the computationally most intricate components, namely the membrane's bending resistance. We start with a short background on the most widely used bending model due to Helfrich. While the Helfrich bending energy by itself is an extremely simple model equation, the computation of the resulting forces is far from trivial. At the heart of these difficulties lies the fact that the forces involve second order derivatives of the local surface curvature which by itself is the second derivative of the membrane geometry. We systematically derive and compare the different routes to obtain bending forces from the Helfrich energy, namely the variational approach and the thin-shell theory. While both routes lead to mathematically identical expressions, so-called linear bending models are shown to reproduce only the leading order term while higher orders differ. The main part of the review contains a description of various computational strategies which we classify into three categories: the force, the strong and the weak formulation. We finally give some examples for the application of these strategies in actual simulations.

Red blood cells flowing through capillaries assume a wide variety of different shapes owing to their high deformability. Predicting the realized shapes is a complex field as they are determined by the intricate interplay between the flow conditions and the membrane mechanics. In this work we construct the shape phase diagram of a single red blood cell with a physiological viscosity ratio flowing in a microchannel. We use both experimental in vitro measurements as well as 3D numerical simulations to complement the respective other one. Numerically, we have easy control over the initial starting configuration and natural access to the full 3D shape. With this information we obtain the phase diagram as a function of initial position, starting shape and cell velocity. Experimentally, we measure the occurrence frequency of the different shapes as a function of the cell velocity to construct the experimental diagram which is in good agreement with the numerical observations. Two different major shapes are found, namely croissants and slippers. Notably, both shapes show coexistence at low (<1 mm s) and high velocities (>3 mm s) while in-between only croissants are stable. This pronounced bistability indicates that RBC shapes are not only determined by system parameters such as flow velocity or channel size, but also strongly depend on the initial conditions.

The physical approach of a small particle (virus, medical drug) to the cell membrane represents the crucial first step before active internalization and is governed by thermal diffusion. Using a fully analytical theory we show that the stretching and bending of the elastic membrane by the approaching particle induces a memory in the system which leads to anomalous diffusion, even though the particle is immersed in a purely Newtonian liquid. For typical cell membranes the transient subdiffusive regime extends beyond 10 ms and can enhance residence times and possibly binding rates up to 50%. Our analytical predictions are validated by numerical simulations.

International audienceOne of the most challenging aspects in the accurate simulation of three-dimensional soft objects such as vesicles or biological cells is the computation of membrane bending forces. The origin of this difficulty stems from the need to numerically evaluate a fourth order derivative on the discretized surface geometry. Here we investigate six different algorithms to compute membrane bending forces, including regularly used methods as well as novel ones. All are based on the same physical model (due to Canham and Helfrich) and start from a surface discretization with flat triangles. At the same time, they differ substantially in their numerical approach. We start by comparing the numerically obtained mean curvature, the Laplace-Beltrami operator of the mean curvature and finally the surface force density to analytical results for the discocyte resting shape of a red blood cell. We find that none of the considered algorithms converges to zero error at all nodes and that for some algorithms the error even diverges. There is furthermore a pronounced influence of the mesh structure: Discretizations with more irregular triangles and node connectivity present serious difficulties for most investigated methods. To assess the behavior of the algorithms in a realistic physical application, we investigate the deformation of an initially spherical capsule in a linear shear flow at small Reynolds numbers. To exclude any influence of the flow solver, two conceptually very different solvers are employed: the Lattice-Boltzmann and the Boundary Integral Method. Despite the largely different quality of the bending algorithms when applied to the static red blood cell, we find that in the actual flow situation most algorithms give consistent results for both hydrodynamic solvers. Even so, a short review of earlier works reveals a wide scattering of reported results for, e.g., the Taylor deformation parameter. Besides the presented application to biofluidic systems, the investigated algorithms are also of high relevance to the computer graphics and numerical mathematics communities

We study the motion of a solid particle immersed in a Newtonian fluid and confined between two parallel elastic membranes possessing shear and bending rigidity. The hydrodynamic mobility depends on the frequency of the particle motion due to the elastic energy stored in the membrane. Unlike the single-membrane case, a coupling between shearing and bending exists. The commonly used approximation of superposing two singlemembrane contributions is found to give reasonable results only for motions in the parallel, but not in the perpendicular direction. We also compute analytically the membrane deformation resulting from the motion of the particle, showing that the presence of the second membrane reduces deformation. Using the fluctuationdissipation theorem we compute the Brownian motion of the particle, finding a long-lasting subdiffusive regime at intermediate time scales. We finally assess the accuracy of the employed point-particle approximation via boundary-integral simulations for a truly extended particle. They are found to be in excellent agreement with the analytical predictions.