Bridging the computational gap between mesoscopic and continuum modeling of red blood cells for fully resolved blood flow

We present a computational framework for the simulation of blood flow with fully resolved red blood cells (RBCs) using a modular approach that consists of a lattice Boltzmann solver for the blood plasma, a novel finite element based solver for the deformable bodies and an immersed boundary method for the fluid-solid interaction. For the RBCs, we propose a nodal projective FEM (npFEM) solver which has theoretical advantages over the more commonly used mass-spring systems (mesoscopic modeling), such as an unconditional stability, versatile material expressivity, and one set of parameters to fully describe the behavior of the body at any mesh resolution. At the same time, the method is substantially faster than other FEM solvers proposed in this field, and has an efficiency that is comparable to the one of mesoscopic models. At its core, the solver uses specially defined potential energies, and builds upon them a fast iterative procedure based on quasi-Newton techniques. For a known material, our solver has only one free parameter that demands tuning, related to the body viscoelasticity. In contrast, state-of-the-art solvers for deformable bodies have more free parameters, and the calibration of the models demands special assumptions regarding the mesh topology, which restrict their generality and mesh independence. We propose as well a modification to the potential energy proposed by Skalak et al. 1973 for the red blood cell membrane, which enhances the strain hardening behavior at higher deformations. Our viscoelastic model for the red blood cell, while simple enough and applicable to any kind of solver as a post-convergence step, can capture accurately the characteristic recovery time and tank-treading frequencies. The framework is validated using experimental data, and it proves to be scalable for multiple deformable bodies

Fluid Vesicles in Flow

We review the dynamical behavior of giant fluid vesicles in various types of external hydrodynamic flow. The interplay between stresses arising from membrane elasticity, hydrodynamic flows, and the ever present thermal fluctuations leads to a rich phenomenology. In linear flows with both rotational and elongational components, the properties of the tank-treading and tumbling motions are now well described by theoretical and numerical models. At the transition between these two regimes, strong shape deformations and amplification of thermal fluctuations generate a new regime called trembling. In this regime, the vesicle orientation oscillates quasi-periodically around the flow direction while asymmetric deformations occur. For strong enough flows, small-wavelength deformations like wrinkles are observed, similar to what happens in a suddenly reversed elongational flow. In steady elongational flow, vesicles with large excess areas deform into dumbbells at large flow rates and pearling occurs for even stronger flows. In capillary flows with parabolic flow profile, single vesicles migrate towards the center of the channel, where they adopt symmetric shapes, for two reasons. First, walls exert a hydrodynamic lift force which pushes them away. Second, shear stresses are minimal at the tip of the flow. However, symmetry is broken for vesicles with large excess areas, which flow off-center and deform asymmetrically. In suspensions, hydrodynamic interactions between vesicles add up to these two effects, making it challenging to deduce rheological properties from the dynamics of individual vesicles. Further investigations of vesicles and similar objects and their suspensions in steady or time-dependent flow will shed light on phenomena such as blood flow.Comment: 13 pages, 13 figures. Adv. Colloid Interface Sci., 201

Active elastohydrodynamics of vesicles in narrow, blind constrictions

Fluid-resistance limited transport of vesicles through narrow constrictions is a recurring theme in many biological and engineering applications. Inspired by the motor-driven movement of soft membrane-bound vesicles into closed neuronal dendritic spines, here we study this problem using a combination of passive three-dimensional simulations and a simplified semi-analytical theory for active transport of vesicles that are forced through such constrictions by molecular motors. We show that the motion of these objects is characterized by two dimensionless quantities related to the geometry and the strength of forcing relative to the vesicle elasticity. We use numerical simulations to characterize the transit time for a vesicle forced by fluid pressure through a constriction in a channel, and find that relative to an open channel, transport into a blind end leads to the formation of an effective lubrication layer that strongly impedes motion. When the fluid pressure forcing is complemented by forces due to molecular motors that are responsible for vesicle trafficking into dendritic spines, we find that the competition between motor forcing and fluid drag results in multistable dynamics reminiscent of the real system. Our study highlights the role of non-local hydrodynamic effects in determining the kinetics of vesicular transport in constricted geometries

Computational studies of biomembrane systems: Theoretical considerations, simulation models, and applications

This chapter summarizes several approaches combining theory, simulation and experiment that aim for a better understanding of phenomena in lipid bilayers and membrane protein systems, covering topics such as lipid rafts, membrane mediated interactions, attraction between transmembrane proteins, and aggregation in biomembranes leading to large superstructures such as the light harvesting complex of green plants. After a general overview of theoretical considerations and continuum theory of lipid membranes we introduce different options for simulations of biomembrane systems, addressing questions such as: What can be learned from generic models? When is it expedient to go beyond them? And what are the merits and challenges for systematic coarse graining and quasi-atomistic coarse grained models that ensure a certain chemical specificity

Viscous regularization and r-adaptive remeshing for finite element analysis of lipid membrane mechanics

As two-dimensional fluid shells, lipid bilayer membranes resist bending and stretching but are unable to sustain shear stresses. This property gives membranes the ability to adopt dramatic shape changes. In this paper, a finite element model is developed to study static equilibrium mechanics of membranes. In particular, a viscous regularization method is proposed to stabilize tangential mesh deformations and improve the convergence rate of nonlinear solvers. The Augmented Lagrangian method is used to enforce global constraints on area and volume during membrane deformations. As a validation of the method, equilibrium shapes for a shape-phase diagram of lipid bilayer vesicle are calculated. These numerical techniques are also shown to be useful for simulations of three-dimensional large-deformation problems: the formation of tethers (long tube-like exetensions); and Ginzburg-Landau phase separation of a two-lipid-component vesicle. To deal with the large mesh distortions of the two-phase model, modification of vicous regularization is explored to achieve r-adaptive mesh optimization