The Relationship Between Aggregation and Deformability of Red Blood Cells in Health and Disease

Abstract

The molecular organization of the membrane of the red blood cell controls cell morphology and function and is thereby a main determinant of red blood cell homeostasis in the circulation. The role of membrane organization is prominently reflected in red blood cell deformation and aggregation. However, there is little knowledge on whether they are controlled by the same membrane property and if so, to what extent. To address the potential interdependence of these two parameters, we measured deformation and aggregation in a variety of physiological as well as pathological conditions. As a first step, we correlated a number of deformability and aggregation parameters in red blood cells from healthy donors, which we obtained in the course of our studies on red blood cell homeostasis in health and disease. This analysis yielded some statistically significant correlations. Also, we found that most of these correlations were absent in misshapen red blood cells that have an inborn defect in the interaction between the membrane and the cytoskeleton. The observations suggest that deformability and aggregation share at least one common, membrane-related molecular mechanism. Together with data obtained after treatment with various agents known to affect membrane organization in vitro, our findings suggest that a phosphorylationcontrolled interaction between the cytoskeleton and the integral membrane protein band 3 is part of the membrane-centered mechanism that plays a role in deformability as well as aggregation.

Role of Purinergic Signalling in Endothelial Dysfunction and Thrombo-Inflammation in Ischaemic Stroke and Cerebral Small Vessel Disease

“…Reactive oxygen species (ROS) release during ischemia damages the membranes of erythrocytes, resulting in increased fragility and reduced maturation and erythrocyte distribution width, which decreases erythrocyte deformability. Rigid erythrocytes tend to aggregate [8], which increases whole blood viscosity [9] and underlies vessel wall shear stress. Shear stress is a mechanical force acting directly on ECs, and disturbances in mechanical forces on ECs affect the NO-synthesizing mechanisms in the vascular endothelium [10].…”

Biomechanics of Ex Vivo-Generated Red Blood Cells Investigated by Optical Tweezers and Digital Holographic Microscopy

“…This allows them to pass through capillaries with diameters smaller than the RBC diameter at rest and restore themselves to their original shape when they leave the capillaries. The deformability of RBCs plays an important role in their main function (transport of respiratory gases in the human body) and alterations in RBC deformability are related to several vascular diseases [ 9 ]. Therefore, cell deformability represents a natural choice to compare ex vivo-cultured red blood cells versus native RBCs.…”

Morphometry and Stiffness of Red Blood Cells—Signatures of Neurodegenerative Diseases and Aging

“…Moreover, the main physiological function of RBCs to deliver oxygen to tissues depends on cell metabolism, cell-cell interactions, deformability and aggregation, with the cell deformability being the crucial factor [ 63 ]. Furthermore, the membrane composition and organization were closely related to cell deformation and aggregation, that is affected by cell morphology, surface properties/membrane surface roughness as well as by the environment [ 63 ]. In fact, the cell membrane is responsible for reversible RBC shape deformations that are essential for their function [ 64 ] and normally healthy cells have higher deformability than diseased ones [ 63 , 65 ].…”

“…Furthermore, the membrane composition and organization were closely related to cell deformation and aggregation, that is affected by cell morphology, surface properties/membrane surface roughness as well as by the environment [ 63 ]. In fact, the cell membrane is responsible for reversible RBC shape deformations that are essential for their function [ 64 ] and normally healthy cells have higher deformability than diseased ones [ 63 , 65 ].…”

“…Importantly, statistically significant correlations between deformability and aggregation parameters determined in healthy RBCs were not found in the distorted RBCs of patients with neuroacanthocytosis [ 63 ]. This was attributed to disturbed phosphorylation-controlled binding between Band 3 containing membrane protein complexes and the cytoskeleton [ 31 , 63 , 68 ].…”