Red Cell Membrane Structure and Function

Red Blood Cells

• Also known as erythrocytes, they have a bi-concave disc shape
• Their role is to transport respiratory gases to and from tissues, specifically delivering oxygen to tissues and removing waste products of metabolism
• On average, a healthy adult male has 5,000,000,000,000 red blood cells per liter of blood

Red Cell Facts

• Red blood cells develop in the bone marrow but lose their nucleus by the time they reach the bloodstream
• They contain hemoglobin, which enables oxygen delivery to tissues
• Red blood cells have an average lifespan of 120 days in the blood circulation, and a reduced lifespan can lead to hemolytic anemia

Function of Red Cell Membrane

• The membrane must be tough but flexible and show deformability to function in microcirculation
• This is achieved by the interaction of a protein cytoskeleton with the membrane lipid bilayer
• The main functions of the red cell membrane are:
  • Separating the cell contents from the plasma
  • Maintaining the characteristic shape of the cell
  • Regulating intracellular cat ion concentrations
  • Serving as a site for membrane surface receptors

The Red Cell Membrane

• Composed of an outer glycocalyx carbohydrate 'coat', a lipid bilayer, and a framework of peripheral proteins that comprise the red cell cytoskeleton
• The glycocalyx is made up of both extracellular proteins and glycosylated proteins and lipids from the lipid bilayer
• The lipid bilayer is made up of 44% lipid, which acts as a permeability barrier and comprises a basic phospholipid bilayer
• The protein component is 49% of the membrane, comprising integral and peripheral proteins that provide skeletal structure and selective transport across the membrane
• The carbohydrate component is 7% of the membrane, associated with proteins or lipids, and presented on the outside of the membrane

Composition of the Red Cell Membrane

• Membrane lipids:
  • 30% cholesterol
  • 60% phospholipid (phosphatidyl choline, sphingomyelin, phosphatidyl ethanolamine, phosphatidyl serine)
  • 10% glycerides/FFA
• Integral proteins:
  • Band 3: facilitates anion transport across the membrane, binding site for skeletal and other red cell proteins
  • Glycophorins (A, B, C, D, E): sialoglycoproteins providing negative charge, acting as binding sites for viruses, bacteria, and parasites, and required for structural integrity of the red cell
  • Glucose Transport Protein: 12 trans-membrane domains, surface concentration varies
  • Rh Proteins: associated into a macrocomplex, transport function, and interact with the cytoskeleton

Peripheral Proteins of the Cytoskeleton

• Spectrin: subunits bind in an anti-parallel arrangement, associates with ankyrin, band 4.1, actin, and anionic phospholipids
• Ankyrin: found in 2 forms, anchors spectrin molecules to the lipid bilayer
• Actin: globular protein that polymerizes readily to form filaments, binds weakly to the tail end of spectrin and holds together in a 2D lattice
• Band 4.1: globular protein that binds to spectrin close to the actin binding site, binds directly to glycophorins A & C, Band 3, phosphatidyl serine, and ankyrin

Red Cell Na+/K+ ATPase 'Cation Pump'

• Enzyme composed of 3 protein subunits, catalyzes the conversion of ATP to ADP to release energy
• ADP formed is reconverted to ATP by the EM Pathway
• Each ATP hydrolyzed removes 3 Na+ molecules and subsequently transports 2 K+ into the cell

Mechanism of Na+/K+ ATPase 'Pump'

• Phosphorylation (energy release) of the pump transports out 3 Na+ molecules
• Dephosphorylation transports 2 K+ into the cell

Primary Membrane Disorders

• Inherited disorders of the red cell membrane
• Affects cell shape, reduced life-span can lead to compensated anemia
• Examples:
  • Hereditary Spherocytosis: autosomal inheritance, results in defective/deficiency of skeletal proteins (mainly spectrin), causes spherocytosis and hemolytic anemia
  • Hereditary Elliptocytosis: presence of a large proportion of oval or elliptical cells, defective spectrin, Band 4.1, or Band 3
  • Rh Null Syndrome: absence of Rh Polypeptides and RhAG in the membrane, stomatocytosis and spherocytosis observed in peripheral blood, patient experiences compensated hemolytic anemia

Learn about the constituents of the red cell membrane, its function, and how its structure enables it to perform its function. Understand how the membrane works to maximize red cell lifespan.