Red Blood Cell Deformability Is Expressed by a Set of Interrelated Membrane Proteins

Abstract

Red blood cell (RBC) deformability, expressing their ability to change their shape, allows them to minimize their resistance to flow and optimize oxygen delivery to the tissues. RBC with reduced deformability may lead to increased vascular resistance, capillary occlusion, and impaired perfusion and oxygen delivery. A reduction in deformability, as occurs during RBC physiological aging and under blood storage, is implicated in the pathophysiology of diverse conditions with circulatory disorders and anemias. The change in RBC deformability is associated with metabolic and structural alterations, mostly uncharacterized. To bridge this gap, we analyzed the membrane protein levels, using mass spectroscopy, of RBC with varying deformability determined by image analysis. In total, 752 membrane proteins were identified. However, deformability was positively correlated with the level of only fourteen proteins, with a highly significant inter-correlation between them. These proteins are involved in membrane rafting and/or the membrane–cytoskeleton linkage. These findings suggest that the reduction of deformability is a programmed (not arbitrary) process of remodeling and shedding of membrane fragments, possibly mirroring the formation of extracellular vesicles. The highly significant inter-correlation between the deformability-expressing proteins infers that the cell deformability can be assessed by determining the level of a few, possibly one, of them.

Red Blood Cell Storage with Xenon: Safe or Disruption?

“…In addition, a 2.5-fold increase in membrane stiffness was observed. The aggregation of band 3 protein results in decreased affinity for the cytoskeletal complex, which in turn increases membrane stiffness and reduces cellular functionality [ 47 , 50 , 53 ]. Erythrocyte stiffness is an important blood flow parameter because stiffer erythrocytes have more difficulty passing through small capillaries to deliver oxygen.…”

Metabolite and protein shifts in mature erythrocyte under hypoxia

“…The reduced deformability of erythrocytes can lead to impaired perfusion, compromised oxygen delivery, and circulatory disturbances. 69 These outcomes can in turn cause hypoxia in the body. Therefore, it is crucial to investigate the mechanisms of erythrocyte deformability not only for hypoxia-related diseases but also for diseases that induce blood stasis.…”

Hemoglobin Binding to the Red Blood Cell (RBC) Membrane Is Associated with Decreased Cell Deformability

“…As in a previous study [40], blood samples were collected from young, nonsmoker, healthy male volunteers (18-37 years) with blood type O+ to obtain a homogeneous population. This selection of volunteers was made to minimize the influence of external factors on the interaction of hemoglobin with the membrane and the cell deformability [17,[72][73][74][75].…”

“…4.2.6. Determination of RBC Deformability RBC deformability was determined using our computerized cell flow-properties analyzer (CFA), as described in our previous studies [2,40,50,71] and illustrated by Figure 3. RBC deformability is measured by directly visualizing the change in the RBC shape in a narrow-gap flow chamber under flow-induced shear stress, expressing the conditions in microvessels.…”