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

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.