Basic Principles of Medicine 1

Module: Foundation to Medicine

DLA

Cellular Organization

E. Koppelman, Ph.D.
St Georges University ©
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Assigned Reading

Histology – A Text and Atlas

Pawlina 7th Edition
Chapter 2: Cell Cytoplasm Pg. 23-38
https://periodicals.sgu.edu/login?url=http://meded.lwwhealthlibrary.com/book.aspx?bookid=1316

Lippincott's Illustrated Reviews: Cell & Molecular Biology

Chandler & Viselli 2010
Chapter 3: Biological Membranes Pg. 26-34
http://meded.lwwhealthlibrary.com/content.aspx?sectionid=49682925&bookid=775
Objectives
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Describe the ultrastructure of the cell membrane.
List the three major classes of membrane lipids.
Describe the structure and function of phospholipids in the plasma membrane.
Describe the structure and function of cholesterol in the plasma membrane.
Describe the structure and function of glycolipids in the plasma membrane.
List the two major classes of membrane proteins.
Describe the categories of integral membrane proteins.
Describe the freeze fracture technique to visualize integral membrane proteins.
Describe the structure and function of the glycocalyx.
Explain the fluid mosaic model of membrane structure.
List the two major types of vesicular transport.
Describe the precise targeting of vesicles within the cell.
List and describe the three different mechanisms of endocytosis.
Describe the role of endosomes in vesicular transport.
List and describe the four pathways for processing internalized ligand-receptor complexes.
List and describe the two general pathways of exocytosis.
 Directed Learning Activity

• Using the Pawlina text, Lippincott’s Cell & Molecular Biology review text
and handout:
1. Describe the components, structure & functions of plasma membranes
2. Describe the types of vesicular transport
3. Answer practice questions in Lippincott’s Cell & Molecular Biology review text
Chapter 3

• Please contact Dr. Koppelman with any questions: ekoppelm@sgu.edu

Generalized Eukaryotic Cell
Structure of Plasma Membrane

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 Membrane Components
1. Lipids
• ~ 50% membrane mass
• Amphipathic
• Hydrophilic
• “Water-loving” polar head
• Hydrophobic
• “Water-fearing” nonpolar tail
• 3 major classes
• Phospholipids
• Cholesterol
• Glycolipids

2. Proteins
• ~ 50% membrane mass
• 2 major classes
• Integral membrane
• Embedded in or pass through the lipid bilayer
• Peripheral membrane
• Associate with integral membrane proteins

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Membrane Lipids SOM.1ai.BPM1.1.FTM.3.HCB.MB.0105

1. Phospholipids
• Most abundant membrane lipid
• Phosphatidylserine
• Phosphatidylethanolamine
• Phosphatidylcholine
• Phosphatidylinositol
• Sphingomyelin

2. Cholesterol
• Major component
• Intercalates between
phospholipids
• Affects membrane fluidity in
temperature dependent manner
Membrane Lipids

3. Glycolipids
• Constitute ~5% of lipid molecules
• Sugar-containing lipid molecules
• Found exclusively in outer monolayer
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Membrane Proteins

1. Integral Membrane Proteins

• Transmembrane (1-3)
• Single pass and multipass
• Anchored (4-6)
• Alpha helix
• Lipid chain
• Oligosaccharide linker

2. Peripheral Membrane Proteins

• Noncovalent association with integral membrane proteins (7-8)
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Integral Membrane Proteins

• 6 General Categories
2. Channels
1. Pumps/Carriers/Transporters
• Transport of ions, small molecules and water
• Transport specific ions across the membrane • Passive diffusion
• Sodium
• Aquaporins
• Potassium
• Water
• Transport metabolic precursors
• Gap junctions
• Amino acids
• Passage of ions, small molecules between adjacent cells
• Sugars

3. Receptors

4. Linkers

5. Enzymes

6. Structural proteins
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Glycocalyx
• Carbohydrate rich zone on the cell surface
• Glycolipids
• Glycoproteins
• Proteoglycans

• Help establish microenvironment at cell

surface

• Protection
• Mechanical damage
• Chemical damage

• Cell recognition

• Cell to Cell Interaction

• Lectins
• Carbohydrate binding proteins
EM x100,000
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Membrane Structure

1. Lipid Bilayer
• Hydrophilic head groups face
exterior and cytosol

• Fatty acid tails create a

hydrophobic core
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Membrane Structure

2. Asymmetry
• Specific phospholipids localize to outer
and inner leaflets

• Significant difference in charge between

the 2 layers

• Phosphatidylserine localizes to the inner

leaflet
• Enzymatically transferred to the outer
leaflet during programmed cell death
• Triggers phagocytic removal of dying cells
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Membrane Structure

3. Lipid rafts
• Specialized cholesterol enriched
microdomains

• Functions
• Signal transduction
• Endocytosis
Membrane Structure
4. Fluid mosaic model
• Fluid membrane
• Lipids and proteins have ability to
move within the plane of the
membrane

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Membrane Properties
• Fluidity
• Membrane lipids and proteins are mobile
• Cholesterol serves to stabilize the membrane
• Reduce membrane fluidity

• Selective Permeability
• Permeable
• Hydrophobic, non-polar, uncharged
• O2, CO2
• Less permeable
• Small, polar, uncharged
• H2O
• Highly impermeable
• Charged (Ions)
• Polar
• Charged

• Transmembrane proteins
• Channels & transporters
• Increase the permeability of the membrane to
molecules that cannot cross the lipid bilayer
 • Exocytosis
Vesicle Transport • Substance exits the cell by the fusion of a vesicle
with the plasma membrane

• Endocytosis
• Substance enters the cell by a vesicle formed from
the plasma membrane
• 3 Types
1. Receptor-mediated
• Cargo-specific
• Clathrin-dependent
2. Pinocytosis
• Non-specific
• Clathrin-independent
3. Phagocytosis
• Clathrin-independent
• Actin-dependent

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Exocytosis

• Regulated
• Secretory cells
• Endocrine
• Exocrine
• Neurons
• Stimulus
• Ca2+ influx
• Fusion of secretory vesicles with plasma membrane

• Constitutive
• Substance for export continuously delivered to
plasma membrane
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Endocytosis 1. Receptor-Mediated Endocytosis

• Selective uptake of large molecules and
particles
• Clathrin-dependent
• Clathrin Coated Pits
• Clathrin molecules interact with cargo
receptors via Adaptin
• Clathrin forms a basket-like cage
• Drives vesicle formation
• Dynamin mediates the vesicle pinching-off
from the plasma membrane
• GTPase
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a. Receptor recycled, ligand degraded c. Receptor and ligand degraded

• Low-density lipoprotein (LDL) receptor • Epidermal growth factor (EGF) & receptor
• Insulin-glucose transporter receptor
• Other peptide hormones & their receptors d. Receptor and ligand transcytosis
• Secretion of immunoglobulins (secretory IgA) into saliva
b. Receptor and ligand recycled • Secretion of maternal IgG into milk
• Iron, transferrin & transferrin receptor
• Major histocompatibility complex I & II
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Vesicle Targeting

• Rab-GTPase interaction with tethering

proteins
• Docking complex
• Rab-GTPase and receptor immobilize
the vesicle near target membrane
• Accurate targeting
• Vesicle-specific membrane protein
• v-SNARE
• Target-specific membrane protein
• t-SNARE
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Endosomes
• Membrane-enclosed structure associated with the
endocytotic pathway

• Early endosome
• Functions to sort and recycle proteins

• Late endosome
• Receives proteins for degradation
• Receives newly synthesized lysosomal enzymes from the
Golgi
• Matures into a lysosome
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Endocytosis

2. Pinocytosis
• “Cell Drinking”
• Non-specific ingestion by small
vesicles
• Constitutive
• Invagination of the plasma
membrane
• No receptor proteins
• Clathrin-independent
• Vesicle pinches-off
• Fusion with lysosome

Pinocytotic vesicles within the endothelial cells of a

blood vessel. EM x55,000
 Endocytosis
3. Phagocytosis
• Ingestion of large particles
• Microorganisms
• Apoptotic cells
• Non-biological materials

• Generally performed by specialized phagocytes

• Macrophage
• Neutrophil

• Particle binds to plasma membrane receptor

• Ex. Antibodies
• Extension of pseudopods
• Dependent on Actin microfilament polymerization
• Phagosome fuses with lysosome
• Digestion
• Residual body
• Indigestible substances

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Phagocytosis