UNIT 6: ERYTHROCYTE MEMBRANE STRUCTURE

oxygen-carbon dioxide transport

The Biconcave disc shape of RBCs facilitates its _ function

90 fL (80-100 fL)

Average volume

Mean Cell Volume (MCV)

Average volume as one of your RBC indices, refers to _

140 um²

Average surface area

40%

The RBC has a _ excess surface area that facilitates easy contact to the tissue hence easier diffusion of oxygen = deformability

5 um thick

RBC Plasma Membrane thickness

Deformability

Allows RCs to adjust to small vessels in the microvasculature and still maintain a constant surface area to volume ratio.

resting diameter

2.5 times

Deformability, it is the capability of RBCs to stretch themselves many more times than their __ with an approximately _

surface area to volume ratio

this significantly affects RBC deformability

↑ surface area ↓ volume

normal surface area to volume ratio of deformable RBC

swelling & lysis

↓ surface area ↑ volume causes RBC _

fragmentation (↓ SA)

lysis (↑ volume)

Changes in the SA : Volume ration causes RBC __ & _

• RBC Geometry

• Relative cytoplasmic (hemoglobin) viscosity → MCHC: 32%-36%

• Membrane elasticity (pliancy)

ENUMERATE

Factors affecting RBC Deformability

low viscosity (fluid)

Normal erythrocyte Hgb concentration has a _

Heinz Bodies

Precipitated hemoglobin

Hb S

Polymerized hemoglobin

Hb C

Crystallized hemoglobin

relative cytoplasmic viscosity

Refers to the HgB concentration relative to the size of the cell

Mean Cell Hemoglobin Concentration (MCHC)

Relative cytoplasmic viscosity, as one your RBC indices, refers to _

↑ aging

↓ ATP & Glycolytic enzymes

no new proteins

↓ SA

Cell volume retained

↑ MCHC

Factors affecting ↓ RBC membrane integrity = ↓ Deformability

T

T or F
RBC membrane is 100% more elastic than latex.

T

T or F

RBC membrane has a higher tensile strength than steel

membrane composition

lipids, carbohydrates, & proteins

Membrane elasticity (pliancy) is attributed the RBC __ (i.e., _ )

1. Serve as a barrier separating the cytoplasm and plasma

2. Allows selective nutrient & ion passage

3. Allows cell deformability when required

3 Basic Functions of the RBC Membrane

function

RBC membrane _ depends on the structure & composition of the membrane.

40%

Lipids account for _ of the membrane composition

phospholipids & cholesterol

Most predominant lipids in the RBC membrane

lipid bilayer leaflet

membrane fluidity

Phospholipids are arranged in a double layer called _ that provides _

liquid sealer

Lipid bilayer leaflet allows the membrane to act as a _

• Phosphatidylcholine

• Sphingomyelin

• Glycolipid (5%)

• Phosphatidylinositol

• Cholesterol

Lipid composition of the outer PM

• Phosphatidylcholine

• Sphingomyelin

Predominant lipids in the external surface (outer PM)

Glycolipid (5%)

sugar bearing lipids; support carbohydrate side chains; anchor glycocalyx; bears blood group antigens.

F

Glycolipids are only found on the OUTER PM

T or F

Glycolipids are present in small amounts in the inner and outer plasma membranes.

Glycocalyx

_ coats the outer membrane

Glycolipids

_ bear different blood group antigens

• Phosphatidylethanolamine

• Phosphatidylserine

• Phosphatidylinositol

• Cholesterol

Lipid composition of the inner PM

• Phosphatidylethanolamine

• Phosphatidylserine

Most predominant phospholipids in the inner membrane

Phosphatidylserine

the ONLY negatively charged phospholipid

ATP dependent.

The ASYMMETRICAL DISTRIBUTION OF PHOSPHOLIPIDS in the RBC membrane is _

T

T or F

Once the ATP generation is compromised, the asymmetrical distribution of phospholipids also become compromised.

Maldistribution of phospholipids

_ in the RBC membrane contribute to the susceptibility of the cell to damage.

1. Scramblases

2. Flippases

3. Floppases

ENUMERATE

These enzymes are ATP dependent and responsible in maintaining the asymmetrical distribution of the cell membrane

Inner PM (containing Phosphatidylserine)

Which PM layer surrounds the nucleus to be expelled during the Orthochromic normoblast stage

• cell stress

• inflammation

• other pathological conditions

Conditions that trigger the phosphatidylserine to be redistributed from the inner to the outer leaflet

CHOLESTEROL

regulates membrane fluidity and membrane permeability

maintains surface area:volume ratio

T

T or F

Cholesterol is present & equally distributed in both layers of the RBC membrane;

and is evenly distributed between the inner and outer leaflets.

• Plasma cholesterol

• bile acids

• activity of LCAT (Lecithin-Cholesterol Acyltransferase)

ENUMERATE

Factors affecting RBC Membrane Cholesterol content

• Acanthocyte

• Codocyte

• Ovalocyte

ENUMERATE

Abnormal RBCs related to Abnormal membrane lipids

Acanthocyte

Abnormal RBC formed due to abnormal lecithin : sphingomyeline ratio

Acanthocyte

→ Few, irregularly distributed projections
→ Spikes have different sizes and shapes
→ Projections are unevenly distributed

Codocyte (Target cell)

contains a characteristic central hemoglobinized area surrounded by pallor and an outer rim

Increased membrane surface area relative to cell volume

Codocyte (Target cell)

Abnormal RBC formed due to ↑ cholesterol and phospholipids

Ovalocyte / Elliptocyte

Abnormal RBC formed due to ↓ cholesterol

Defects in RBC membrane proteins (pectrin and protein 4.1.)

tensile strength

↑ cholesterol ↑ membrane strength ↓ elasticity

Cholesterol confers _ to the lipid bilayer

GLYCOCALYX

layer of carbohydrates whose net negative charge prevents microbial attack and protects the RBC from mechanical damage— particularly once in the circulation

Glycocalyx

_ are surface carbohydrates joined with glycolipids

8%

% composition of carbohydrates in RBC membrane

52%

% composition of proteins in RBC membrane

sialic acid

Integral Proteins/ Transmembrane Proteins contains _ which gives RBCs a negative charge

Integral Proteins/Transmembrane Proteins

Proteins that penetrate the phospholipid bilayer.

Provides vertical membrane structure

zeta potential

the repulsive force that repels RBC from each other

1. Transport sites

2. Adhesion sites

3. Signaling receptors

ENUMERATE

Functions of Integral Proteins/Transmembrane Proteins

Band 3

Principal (most abundant) integral protein

1. Ankyrin complex

2. Protein 4.1 complex / Actin junctional complex

ENUMERATE

2 macromolecular complexes of integral proteins

• band 3 (multimers)

• protein 4.2

ENUMERATE

Major components of Ankyrin complex

spectrin cytoskeleton

ankyrin protein

Ankyrin complex anchor the phospholipid bilayer to the __ through the _.

• band 3 (dimers)

• protein 4.2

• adducin

• actin

ENUMERATE

Major components of Protein 4.1 complex / Actin Junctional Complex

protein 4.1.

Protein 4.1 complex anchor the phospholipid bilayer to the spectrin cytoskeleton through the _

T

T or F

Both protein complexes prevent loss of the lipid bilayer.

They serve as the bridge between the lipid bilayer and the cytoskeleton proteins, particularly the spectrin.

spectrin cytoskeleton

Protein 4.1 complex

The cross linking of the __ and the protein _ makes the shape of the RBC intact in order to maintain its biconcave shape.

• Aquaporin 1

• Band 3

• Ca²⁺-ATPase

• Glut-1

• ICAM-4

• NA⁺,K⁺-ATPase

Enumerate

MUST KNOWS TRANSMEMBRANE RBC PROTEINS

Aquaporin 1

TRANSMEMBRANE RBC PROTEINS

• Water transporter

Aquaporin 1

TRANSMEMBRANE RBC PROTEINS

• Colton antigen

Band 3

TRANSMEMBRANE RBC PROTEINS

• Anion transporter

Band 3

TRANSMEMBRANE RBC PROTEINS

• location of ABH antigens

Ca²⁺-ATPase

TRANSMEMBRANE RBC PROTEINS

• Ca2+ transporter

Glut-1

TRANSMEMBRANE RBC PROTEINS

• Glucose transporter

Glut-1

TRANSMEMBRANE RBC PROTEINS

• location of ABH blood group antigens

ICAM-4

TRANSMEMBRANE RBC PROTEINS

• Integrin adhesion

Na⁺, K⁺-ATPase

TRANSMEMBRANE RBC PROTEINS

• Na+, K+ transporter

Peripheral Proteins/Cytoskeletal Proteins

Proteins that do not penetrate the phospholipid bilayer.

Only present on the inner side/layer of the PM

Peripheral Proteins/Cytoskeletal Proteins

Provides lateral/horizontal membrane stability

• α-spectrin → Band 1

• β-spectrin → Band 2

Principal cytoskeletal protein

20

16

The cytoskeleton is mainly composed of __ alpha-spectrin and _ beta-spectrin

T

T or F

Spectrins can fold & unfold, change its conformation, allowing the cytoskeleton to stretch and recoil = Flexibility

• Spectrin stabilization

• Membrane deformation

ENUMERATE

Functions of cytoskeletal proteins

• α-spectrin

• β-spectrin

• Adducin

• Ankyrin

• Dematin

• β-actin

• G3PD

• Protein 4.1

• Protein 4.2

• Tropomodulin

• Tropomyosin

ENUMERATE

CYTOSKELETAL RBC PROTEINS

α-spectrin, β-spectrin

CYTOSKELETAL RBC PROTEINS

• Filamentous antiparallel heterodimer

α-spectrin, β-spectrin

CYTOSKELETAL RBC PROTEINS

• Primary cytoskeletal proteins

Adducin

CYTOSKELETAL RBC PROTEINS

• Caps actin filament

Adducin

CYTOSKELETAL RBC PROTEINS

• Binds Calcium ions / Calmodulin

Ankyrin

CYTOSKELETAL RBC PROTEINS

• Anchors band 3, protein 4.2, and other proteins in the ankyrin complex to spectrin

Dematin

CYTOSKELETAL RBC PROTEINS

• Actin bundling protein

β-actin

CYTOSKELETAL RBC PROTEINS

• Binds β-spectrin

G3PD

CYTOSKELETAL RBC PROTEINS

• Carbohydrate metabolism

G3PD

CYTOSKELETAL RBC PROTEINS

• Phosphorylates G3P

Protein 4.1

CYTOSKELETAL RBC PROTEINS

• Anchors the actin junctional complex to spectrin tetramers

Protein 4.1

CYTOSKELETAL RBC PROTEINS

• RBC skeleton shape

Protein 4.2 (Protein kinase)

CYTOSKELETAL RBC PROTEINS

• Part of ankyrin complex

• ATP binding protein

Tropomodulin

CYTOSKELETAL RBC PROTEINS

• Caps actin filament