Rbc membrane deformability

RBCs are biconcave and average 90 fL in volume.

• Their average surface area is 140 μm2, a 40% excess of surface area
compared with a 90-fL sphere. This excess surface-to-volume ratio
enables RBCs to stretch undamaged up to 2.5 times their resting
diameter as they pass through narrow capillaries and through splenic
pores 2 μm in diameter; this property is called RBC deformability.
• The RBC plasma membrane, which is 5 μm thick, is 100 times more
elastic than a comparable latex membrane, yet it has tensile (lateral)
strength greater than that of steel.
• The deformable RBC membrane provides the broad surface area and
close tissue contact necessary to support the delivery of O2 from lungs
to body tissue and CO2 from body tissue to lungs.
• RBC deformability depends not only on RBC geometry but also on
relative cytoplasmic (hemoglobin) viscosity. The normal mean cell
hemoglobin concentration (MCHC) ranges from 32% to 36%, and as
MCHC rises, internal viscosity rises. MCHCs above 36% compromise
deformability and shorten the RBC life span because viscous cells
become damaged as they stretch to pass through narrow capillaries
or splenic pores. As RBCs age, they lose membrane surface area,
while retaining hemoglobin. As the MCHC rises, the RBC, unable to
pass through the splenic pores, is destroyed by splenic macrophages.
Rbc membrane lipids
Besides geometry and viscosity, membrane elasticity (pliancy) also contributes to
deformability.
The RBC membrane consists of approximately:
1. 8% carbohydrates
2. 52% proteins
3. 40% lipids.
The lipid portion, equal parts of cholesterol and phospholipids, forms a bilayer universal
to all animal cells. Phospholipids form an impenetrable fluid barrier as their hydrophilic
polar head groups are arrayed upon the membrane’s surfaces, oriented toward both the
aqueous plasma and the cytoplasm, respectively. Their hydrophobic nonpolar acyl tails
arrange themselves to form a central layer dynamically sequestered (hidden) from the
aqueous plasma and cytoplasm. The membrane maintains extreme differences in
osmotic pressure, cation concentrations, and gas concentrations between external
plasma and the cytoplasm. Phospholipids reseal rapidly when the membrane is torn.
• Cholesterol, esterified and largely hydrophobic, resides parallel to the
acyl tails of the phospholipids, equally distributed between the outer
and inner layers, and evenly dispersed within each layer,
approximately one cholesterol molecule per phospholipid molecule.
Cholesterol’s β-hydroxyl group, the only hydrophilic portion of the
molecule, anchors within the polar head groups, while the rest of the
molecule becomes intercalated among and parallel to the acyl tails.
Cholesterol confers tensile strength to the lipid bilayer.
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The ratio of cholesterol to
phospholipids remains
relatively constant and balances
the need for deformability and
strength. Membrane enzymes
maintain the cholesterol
concentration by regularly
exchanging membrane and
plasma cholesterol. Deficiencies
in these enzymes are
associated with membrane
abnormalities such as
acanthocytosis, as the https://images.app.goo.gl/yNxgTxjizz4ZHa398
membrane loses tensile
strength. Conversely, as
cholesterol concentration rises,
the membrane gains strength
but loses elasticity.
• The phospholipids are asymmetrically distributed.
Phosphatidylcholine and sphingomyelin predominate in the outer
layer; phosphatidylserine (PS) and phosphatidylethanolamine form
most of the inner layer. Distribution of these four phospholipids is
energy dependent, relying on a number of membrane-associated
enzymes, whimsically termed flippases, floppases, and scramblases,
for their positions.
• When phospholipid distribution is disrupted, as in sickle cell anemia
and thalassemia or in RBCs that have reached their 120-day life
span, PS, the only negatively charged phospholipid, redistributes
(flips) to the outer layer. Splenic macrophages possess receptors that
bind PS and destroy senescent and damaged RBCs.
Membrane phospholipids and
cholesterol may also redistribute
laterally so that the RBC membrane may
respond to stresses and deform within
100 milliseconds of being challenged by
the presence of a narrow passage, such
as when arriving at a capillary.
Redistribution becomes limited as the
proportion of cholesterol increases.
Plasma bile salt concentration also
affects cholesterol exchange. In liver
disease with low bile salt concentration,
membrane cholesterol concentration
becomes reduced. As a result, the more
elastic cell membrane shows a “target
https://images.app.goo.gl/3ueu5YDwhKtQFCiE6
cell” appearance when the RBCs are
layered on a glass slide.
• Glycolipids (sugar-bearing lipids) make up 5% of the external half of
the RBC membrane. They associate in clumps or rafts and support
carbohydrate side chains that extend into the aqueous plasma to
anchor the glycocalyx. The glycocalyx is a layer of carbohydrates
whose net negative charge prevents microbial attack and protects the
RBC from mechanical damage caused by adhesion to neighboring
RBCs or to the endothelium. Glycolipids may bear copies of
carbohydrate-based blood group antigens, for example, antigens of
the ABH and the Lewis blood group systems.
Rbc membrane proteins

Although cholesterol and phospholipids constitute the principal RBC

membrane structure, transmembrane (integral) and cytoskeletal
(skeletal, peripheral) proteins make up 52% of the membrane structure
by mass. A proteomic study reveals there are at least 300 RBC
membrane proteins, including 105 transmembrane proteins. Of the
purported 300 membrane proteins, about 50 have been characterized
and named, some with a few hundred copies per cell, and others with
over a million copies per cell
Transmembrane proteins

• The transmembrane proteins serve a number of RBC functions. Through

glycosylation they support surface carbohydrates, which join with glycolipids
to make up the protective glycocalyx. They serve as transport and adhesion
sites and signaling receptors. Any disruption in transport protein function
changes the osmotic tension of the cytoplasm, which leads to a rise in
viscosity and loss of deformability. Any change affecting adhesion proteins
permits RBCs to adhere to one another and to the vessel walls, promoting
fragmentation (vesiculation), reducing membrane flexibility, and shortening
the RBC life span. Signaling receptors bind plasma ligands and trigger
activation of intracellular signaling proteins, which then initiate various
energy-dependent cellular activities, a process called signal transduction.
Skeletal Proteins Functions
α-spectrin Filamentous antiparallel heterodimer, primary
β-spectrin cytoskeletal proteins

Adducin Caps actin filament

Ankyrin Anchors band 3 and protein 4.2
Dematin Actin bundling protein
F-actin Binds β-spectrin
G3PD
Protein 4.1 Anchors 4.1 complex
Protein 4.2 (protein kinase) Anchors ankyrin complex
Tropomodulin Caps actin filament
Tropomyosin Regulates actin polymerization
Osmotic balance and permeability
• The RBC membrane is impermeable to cations Na+, K+, and Ca2+. It is
permeable to water and the anions bicarbonate (HCO3−) and chloride
(Cl−), which freely exchange between plasma and RBC cytoplasm.
Aquaporin 1 is a transmembrane protein that forms pores or channels
whose surface charges create inward water flow in response to internal
osmotic changes.
• The ATP–dependent cation pumps Na+ -ATPase and K+ -ATPase regulate
the concentrations of Na+ and K+, maintaining intracellular-to-
extracellular ratios of 1:12 and 25:1, respectively. Ca2+ -ATPase extrudes
calcium, maintaining low intracellular levels of 5 to 10 μmol/L.
Calmodulin, a cytoplasmic Ca2+-binding protein, controls the function of
Ca2+-ATPase. These enzymes, in addition to aquaporin, maintain
osmotic balance.
• The cation pumps consume 15% of RBC ATP production. ATP loss or
pump damage permits Ca2+ and Na+ influx, with water following
osmotically. The cell swells, becomes spheroid, and eventually
ruptures. This phenomenon is called colloid osmotic hemolysis.

• Sickle cell disease provides an example of increased cation

permeability. When crystallized sickle hemoglobin deforms the cell
membranes, internal levels of Na+, K+, and especially Ca2+ rise, which
results in hemolysis
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