Do red blood cells have a net negative surface charge?

Red Blood Cell Surface Charge

Red blood cells carry a net negative surface charge, primarily due to sialic acid residues on membrane glycoproteins, particularly glycophorin A. 1, 2

Molecular Basis of Negative Charge

The negative charge on red blood cells originates from two main sources:

• Sialic acid carboxyl groups are the principal determinants of the negative surface charge, located on the outer surface of the plasma membrane as components of glycoproteins 1, 2
• Phosphate groups also contribute to the overall negative charge, though to a lesser extent than sialic acid 1
• The major carrier of sialic acid is glycophorin A, the most abundant erythrocyte membrane glycoprotein 3

Functional Significance

The negative charge serves critical physiological functions:

• Electrostatic repulsion between cells prevents spontaneous red blood cell aggregation under normal conditions 3, 2
• This repulsive force creates a zeta potential that maintains appropriate spacing between circulating erythrocytes 2
• The negative charge reduces blood viscosity at low shear rates by preventing cell clumping 3

Clinical Relevance

Disease States

• Diabetes mellitus is associated with decreased glycophorin sialic acid content (median 3.30 vs 18.60 μg/100 μg protein in controls), leading to increased erythrocyte aggregation 3
• The reduction in sialic acid correlates statistically with increased red blood cell aggregation (r = 0.73, P < 0.05) 3

Cell Senescence and Clearance

• Enzymatic removal of sialic acid with neuraminidase reduces electrophoretic mobility by approximately 40%, demonstrating the charge contribution of these residues 1
• Desialylated red blood cells undergo rapid hepatic clearance when transfused, suggesting this may be a mechanism for removal of senescent cells 4
• However, normal senescent red blood cells maintain their sialic acid content (within ±1.5% of young cells), indicating they are cleared by mechanisms other than desialylation 5

Interaction with Nanoparticles

• The negatively charged red blood cell surface interacts differently with charged nanoparticles: cationic nanoparticles readily interact with the anionic cell membrane, while anionic nanoparticles (zeta potential < -20 mV) are more readily taken up by the reticuloendothelial system 6
• Cancer cell membranes can overexpress negatively charged phospholipids, and this principle extends to understanding cellular interactions with charged particles 6

Practical Applications in Transfusion Medicine

• Enhancement solutions used in blood banking work by modulating the negative charge: enzymes reduce the negative charge to promote agglutination, while LISS improves antibody binding 2
• Understanding red blood cell electrical properties is essential for optimizing the specificity and sensitivity of immunohematological reactions 2