A Hybrid Model for Erythrocyte Membrane: A Single Unit of Protein Network Coupled with Lipid Bilayer

Abstract

To investigate the nanomechanics of the erythrocyte membrane we developed a hybrid model that couples the actin-spectrin network to the lipid bilayer. This model features a Fourier space Brownian dynamics model of the bilayer, a Brownian dynamics model of the actin protofilament, and a modified wormlike-chain model of the spectrin (including a cable-dynamics model to predict the oscillation in tension). This model enables us to predict the nanomechanics of single or multiple units of the protein network, the lipid bilayer, and the effect of their interactions. The present work is focused on the attitude of the actin protofilament at the equilibrium states coupled with the elevations of the lipid bilayer through their primary linkage at the suspension complex in deformations. Two different actin-spectrin junctions are considered at the junctional complex. With a point-attachment junction, large pitch angles and bifurcation of yaw angles are predicted. Thermal fluctuations at bifurcation may lead to mode-switching, which may affect the network and the physiological performance of the membrane. In contrast, with a wrap-around junction, pitch angles remain small, and the occurrence of bifurcation is greatly reduced. These simulations suggest the importance of three-dimensional molecular junctions and the lipid bilayer/protein network coupling on cell membrane mechanics.

Erythrocyte Tropomodulin Isoforms with and without the N-terminal Actin-binding Domain

“…Because ␣ and ␤ spectrin intertwine side-by-side in an anti-parallel fashion and the C terminus of ␣ spectrin (repeats 20 -21) interacts with the N terminus of ␤ spectrin (51), their dimerization may block the ubiquitin-recognizing sites in ␣ spectrin (50). How ␣ and ␤ spectrin at its tail region may wrap around F-actin in a JC has been proposed (28).…”

“…There, we reported the first three-dimensional model for a JC and how each pair of G-actin may be wrapped around by a split ␣ and ␤ spectrin (Sp) and stabilized by 4.1R, forming a basic repeating unit (26). This model allows the three-dimensional nano-mechanics of a JC or a basic unit to be simulated in terms of the attitude (pitch, yaw, and roll angles) of the protofilament and the tension of each radiating Sp (in pN) during equibiaxial and anisotropic deformations (27,28).…”

Prospects for Human Erythrocyte Skeleton-Bilayer Dissociation during Splenic Flow

“…In the following, we briefly describe the primary characteristics of these models. The details are included in our previous publications (18,(32)(33)(34).…”

“…the bending stiffness) are taken from reported values in the literature (see Table 1). The properties of the cytoskeleton (specifically, its area and shear stiffness) are obtained from a mesoscale model of the 3D molecular architecture of a junctional complex (JC), the basic unit in the cytoskeleton (33). The JC contains a central piece of actin protofilament (modeled as a rigid rod) surrounded by six flexible spectrin dimers (Sp), modeled as nonlinear springs, as described in the following paragraph.…”

Rate-type elasticity and viscoelasticity of an erythrocyte membrane

“…Section 2 contains the kinematics and kinetics of the membrane in-plane deformation. The Evans-Skalak form of the elastic strain energy is adopted, as in most other recent work on the mechanics of red blood cell, (e.g., [Mills et al 2004;Zhu et al 2007]). The rate-type elasticity equations, which relate the Jaumann rate of the Kirchhoff stress to the rate of deformation tensor, are derived in Section 3.…”