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 phosphorylation-controlled 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.
Highlights
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
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
In the course of our studies on red blood cell (RBC) homeostasis in health and disease, we have accumulated deformability and/or aggregation data of RBCs with various biological backgrounds, such as RBCs of different ages isolated from the circulation of healthy donors (Willekens et al, 2008; Freitas Leal et al, 2019), RBCs of different storage periods in the blood bank (Cluitmans et al, 2012), acanthocytes and otherwise misshapen RBCs from patients with neuroacanthocytosis (De Franceschi et al, 2011; Cluitmans et al, 2015), and RBCs treated with various membrane organizationaffecting agents (Dinkla et al, 2012; Cluitmans et al, 2016)
Summary
Tissue oxygenation depends on hemoglobin as much as on red blood cell (RBC) characteristics such as metabolism, communication with the immune system, deformability and aggregation behavior. Many RBC-centered pathologies such as deficiencies in metabolic enzymes, altered hemoglobins, and mutations in membrane proteins affect the same processes that play a critical role in physiological aging, and are associated with decreased deformability, as well (Alaarg et al, 2013; Mohandas, 2017). This may be due directly to weakening of the interactions between membrane and/or cytoskeleton proteins, or to the resulting loss of membrane by vesiculation (Huisjes et al, 2018). Changes in aggregation are often accompanied by changes in deformability, and sometimes by changes in cell shape as well (Xue et al, 2013; Li et al, 2014)
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