Structural and mechanical properties of the red blood cell’s cytoplasmic membrane seen through the lens of biophysics

Abstract

Red blood cells (RBCs) are the most abundant cell type in the human body and critical suppliers of oxygen. The cells are characterized by a simple structure with no internal organelles. Their two-layered outer shell is composed of a cytoplasmic membrane (RBCcm) tethered to a spectrin cytoskeleton allowing the cell to be both flexible yet resistant against shear stress. These mechanical properties are intrinsically linked to the molecular composition and organization of their shell. The cytoplasmic membrane is expected to dominate the elastic behavior on small, nanometer length scales, which are most relevant for cellular processes that take place between the fibrils of the cytoskeleton. Several pathologies have been linked to structural and compositional changes within the RBCcm and the cell’s mechanical properties. We review current findings in terms of RBC lipidomics, lipid organization and elastic properties with a focus on biophysical techniques, such as X-ray and neutron scattering, and Molecular Dynamics simulations, and their biological relevance. In our current understanding, the RBCcm’s structure is patchy, with nanometer sized liquid ordered and disordered lipid, and peptide domains. At the same time, it is surprisingly soft, with bending rigidities κ of 2–4 kBT. This is in strong contrast to the current belief that a high concentration of cholesterol results in stiff membranes. This extreme softness is likely the result of an interaction between polyunsaturated lipids and cholesterol, which may also occur in other biological membranes. There is strong evidence in the literature that there is no length scale dependence of κ of whole RBCs.

In vitro investigation of the mechanics of fixed red blood cells based on optical trap micromanipulation and image analysis

“…To examine the deformability of diseased erythrocytes, the red blood cells were treated with glutaraldehyde to modify their shear moduli, thereby simulating “diseased” erythrocytes. The erythrocyte cell membrane consists of a phospholipid bilayer and a cell membrane protein backbone on its inner surface [ 41 ]. Upon exposure to glutaraldehyde, the fluidity of the phospholipid bilayer decreases, leading to the cross-linking of cell membrane proteins into dimers or trimmers [ 42 ] as well as an elevated shear modulus of erythrocytes.…”

Characterizing morphological alterations in blood related disorders through Atomic Force Microscopy

“…Himbert S. et al, investigated the biomechanical characteristics of both kinds of particles in liquid and air using the atomic force microscope technology. Bruker's Bioscope Catalyst and Bioscope Resolve microscopes in PeakForce QNM mode were used to do the measurements in both liquid and air 91 .…”

OMEF biochip for evaluating red blood cell deformability using dielectrophoresis as a diagnostic tool for type 2 diabetes mellitus

“…The mechanical properties of the RBC membrane have been characterized through various properties, including shear, area compressibility, bending, and elasticity. 14,[23][24][25] Currently, there are several techniques available to analyse the alterations in RBCs at the single-cell level, such as glass microneedles, 26 optical and magnetic tweezers, 27 convergingdiverging microfluidic channels, 23 and atomic force microscopy (AFM). 28 While these single-cell approaches provide high precision, they have limitations including low throughput and slow processing speed.…”