RBC Membrane

Red cell membrane

Alick Mwambungu

Red cell membrane

The primary function of the red cell is the transport of respiratory gases to and from the tissues.

To achieve this task the red cell should be capable of traversing the microvascular system without mechanical damage,

and that the cell should retain a shape which facilitates gaseous exchange.

Red cell membrane

In order to meet with the demands of function, the red cell membrane should be extremely tough yet highly flexible.

This strength and flexibility of the red cell membrane is due to the design of its protein cytoskeleton and the way the cytoskeleton interacts with the membrane lipid bilayer.

Functions of red cell membrane

oTo separate the contents of the cell from the plasma.

To maintain the characteristic shape of the red cell.

To regulate intracellular cation conc.To act as the interface between the cell and its environment via membrane surface receptors.

Red cell membrane

The red cell membrane consists of: Proteins~50% Lipids ~ 40% Carbohydrates~10%

General structure of a Cell Membrane

Composition of the red cell membrane

MEMBRANE CARBOHYDRATES

They occur only on the external surface of the red cell.

They occur as glycoprotein and glycolipids. The antigens of the ABO blood group are

examples of membrane carbohydrates.

Composition of the RBC memb. (cont.)

Membrane Lipids Lipid components of the red cell

membrane are: 30% free unesterified cholesterol. 10% Glycerides and free fatty

acids. 60% Phospholipids

Membrane Phospholipids

Phospholipids are fat derivatives in which one fatty acid has been replaced by a phosphate group and one of several nitrogen-containing molecules.

Phospholipid molecules are characterized by a polar head group attached to a non-polar fatty acid tail.

Membrane Phospholipids

The polar head group is hydrophilic (water loving)

The charges on the phosphate and amino groups make that portion of the molecule hydrophilic

The fatty acid tail(Hydrocarbon chains) is hydrophobic (water fearing).

RBC Membrane Phospholipids

Thus the phospholipids in the cell membrane tend to arrange themselves in a bilayer.

Hydrophilic heads pointing towards the inner and outer aqueous phases ( the cytoplasmic and extracellular phase),

The hydrophobic tails point towards each other.

The red cell membrane phospholipids, are: Phosphatidyl choline(Lethicin), Phosphatidyl ethanolamine, Sphingomyelin and Phosphatidyl serine

Phosphatidyl ethanolamine

Phosphatidyl Serine

RBC Membrane Phospholipids

The choline phospholipids-Phosphatidyl choline and sphingomyelin are mainly present in the extracellular layer.

Amino phospholipids-Phosphatidyl ethanolamine and phosphatidyl serine are restricted to the cytoplasmic layer.

Membrane Cholesterol

The membrane cholesterol is unesterified and lies between the two layers of the lipid bilayer.

The cholesterol molecule inserts itself in the membrane with the same orientation as the phospholipid molecules.



The concentration of cholesterol in the membrane is an important determinant of membrane surface area and fluidity.

An increase in membrane cholesterol leads to an increased surface area and decreased deformability.

In extreme circumstances, decreased deformability can lead to premature RBC destruction.

Composition of the red cell

Membrane Proteins These are either: -Peripheral or -Integral

Membrane Proteins

RBC membrane proteins have been named according to their relative positions on SDS-PAGE electrophoresis

A, gel stained with • coomassie blue

B, drawing of the positions of some major proteins

SDS-PAGE separation of red blood cell proteins after

Glycophorin labled indicating it is exposedon the outer surface of themembrane

Red cell membrane proteins

Peripheral Proteins The red cell peripheral proteins interact to

form a cytoskeleton. The cytoskeleton acts as a tough

supporting framework for the lipid bilayer. Four peripheral proteins play a key role in

the structure of the red cell cytoskeleton: - Spectrin - Ankyrin - Protein 4.1 and - Actin

Red Cell Membrane


Spectrin(Bands 1 and 2) Is the most abundant membrane protein consists of two chains, and , wound

around each other to form heterodimers which then self-associate head to head to form tetramers.

These tetramers are linked at the tail end to actin and are attached to protein band 4.1.

At the head end, the -spectrin chains attach to ankyrin which connects to band 3(anion channel). Protein 4.2 enhances this interaction.

Red Cell Membrane Proteins

Ankyrin(Bands 2.1-2.3) This serves to anchor assembled spectrin

molecules to the lipid bilayer. Accomplished by binding simultaneously

to the spectrin tetramers and to the interior domain of the integral protein-Band3


Actin(Band 5) It is a globular protein Composed of filaments The filaments bind weakly to the tail end

of both and spectrins.

Red Cell Membrane proteins

Band 4.1 It’s a globular protein Binds to spectrin close to the actin

binding site thereby strengthening and stabilizing the cytoskeletal lattice.

Band 4.1 Cont....

Also binds directly to Glycophorins A and C and Band3.

It therefore strengthens the links between the lipid bilayer and the protein cytoskeleton.


Integral Proteins

These penetrate the lipid bilayer and are firmly anchored within it.

-Band 3 -Glycophorins A, B, and C. -Na+/K+ ATPase. -glucose transport protein. -surface receptors.


BAND 3o It is a single molecule with a molecular

weight of 95000.o It accounts for 25% of total protein

content of the RBC membrane.o Has two major functions within the red

cell membrane: 1-To facilitate anion transport via the red

cell membrane. 2- It is an important binding site for

cytoskeletal and other red cell proteins.

Red Cell Membrane

Glycophorins Three members of the RBC glycophorin

family: Glycophorins-A,B and C These are sialoglycoproteins. A sialoglycoprotein is a combination of

sialic acid and glycoprotein (which is, itself, a combination of a sugar and protein)


Glycophorins act as transmembrane signal transducers.

Also acts as the receptor for the Plasmodium falciparum protein PfEBP-2 (erythrocyte binding protein 2)


Na+/K+ ATPase This enzyme catalyses the hydrolysis of

ATP to ADP, liberating energy in this process.

Each ATP molecule hydrolysed via this system results in the ejection of three Na+ ions from the cell and the transport of two K+ ions into the cell.

Na/K ATPase pump Mechanism

Na/K ATpase pump Mechanism

The pump, with bound ATP, binds 3 intracellular Na+ ions.

ATP is hydrolyzed, leading to phosphorylation of the pump and subsequent release of ADP.

A conformational change in the pump exposes the Na+ ions to the outside.

The phosphorylated form of the pump has a low affinity for Na+ ions, so they are released.

Na/K ATpase Pump

The pump binds 2 extracellular K+ ions. This causes the dephosphorylation of the pump,

reverting it to its previous conformational state, transporting the K+ ions into the cell.

The unphosphorylated form of the pump has a higher affinity for Na+ ions than K+ ions.

the two bound K+ ions are released. ATP binds, and the process starts again.

Glucose transport Protein

Has a molecular weight of 60 000. ATP hydrolysis not required for Glucose

transport Motive force for transport of plasma

Glucose into the red cell is derived from the electrochemical gradient of Na+ ions across the cell membrane.

Membrane Proteins

Each molecule of Glucose transported into the cell is accompanied by a Na+ ion

Leading to a net reduction in the transmembrane gradient of Na+ ions.

Failure of the cation pump to regenerate the Na+ gradient ,would result in failure of Glucose transport.

May lead to glycolytic failure and hence lack of ATP generation.

Final result-cell death.

Surface receptors

Most important surface receptor is transferrin receptor.

Though present on most of the cells The highest conc is on RBC surface. The receptor domain is capable of binding

two transferrin molecules. Receptor-transferrin complexes are

internalised. Iron released from the transferrin

Blood group antigens

o These are antigens found on the red cell

membrane, they are responsible for the determination of the blood group of the individual.

Blood group antigens are found on both the protein and the carbohydrate components of the membrane glycoproteins and the glycolipids.

Abnormalities of the RBC membrane

Hereditary sherocytosis-Decrease in surface area to volume ratio.

May be as a result of defective cytoskeletal proteins.

Hereditary Elliptocytosis-Abnormal membrane cholesterol distribution or Abnormalities in the or spectrin subunits.

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RBC Membrane