Lecture Handouts - Cell-Cell Adhesion

Asst Prof. Dr. Sidra Arshad

Physiology, 1st Year MBBS 2024

Learning Objectives:
1. Describe the cell to extracellular and cell to cell connections
2. Describe the functions of cell adhesion molecules
3. Discuss the characteristics and functions of intercellular connections

• Cells organized into appropriate groupings are held together by three different means:
1. The extracellular matrix
2. CAMs (Cell Adhesion Molecules)
3. Specialized cell junctions

The Extracellular Matrix

• Tissues = cells + matrix
• Not all cells in contact with each other
• Instead, held together by a biological “glue” – the ECM
• ECM = meshwork of fibrous proteins + carbohydrate-rich
watery gel
• Collagen (provide tensile strength), elastin (more abundant
in tissues which require elasticity for their functions, e.g.
lungs) and fibronectin are major types of protein fibers
• Abundant in connective tissue
• Less in epithelial tissue
Cell Adhesion Molecules (CAMs)
Cells are attached to the basal lamina and to each other by CAMs
Functions of CAMs:
1. Embryonic development – temporary connections (nonjunctional contacts), allow locomotion
2. Hold tissues together – by associating with cell junctions and ECM in adults
3. Transmit signals into and out of cells
4. Inflammation and wound healing
5. Prevent metastasis of tumors

Divided into four broad families:

1. Integrins
2. Adhesion molecules of the IgG superfamily of immunoglobulins
3. Cadherins
4. Selectins

Integrins • Heterodimers
• Can bind to receptors (ligands)
• Span the plasma membrane
• Serve as a structural link between the outer membrane surface and its extracellular surroundings
Selectins • Have lectin-like domains that bind carbohydrates
• Mediate cell-cell adhesion interactions in the bloodstream
• Together with integrins, important in inflammatory response
Cadherins • Ca2+ - dependent molecules
• Mediate cell-to-cell adhesion by homophilic reactions – bind with similar molecules
• Important in embryogenesis
• Prevent tumor invasion
IgG Superfamily • Have immunoglobulin (anti-bodies) like domains
• Important in cellular organization during embryogenesis
Types of Cell Junctions

Type Structure Location Functions

Zonula occludens • Apposed ridges (thickened cytoplasm) at the apical margins of the • Keep cells polarized
from adjacent cells cells in epithelial sheets - • Prevent movement of
• Major proteins: occludins, junctional intestinal mucosa, walls of the materials between the cells
adhesion molecules, claudins renal tubules, and the choroid
plexus

Zonula adherens • A belt that encircles an entire epithelial at the apical margins of the • Provide epithelial cells with
cell just below the level of the tight cells in epithelial sheets - clues about the nature and
junction intestinal mucosa, walls of the proximity of their neighbors
• A major site of attachment for renal tubules, and the choroid • Initiate cytoskeletal assembly
intracellular microfilaments plexus
• Contains cadherins

Desmosomes/Macula adherens • Patches characterized by apposed skin, heart, uterus • Connect the adjacent cells
thickenings of the membranes of two • Provide a passageway to ions
adjacent cells to create a quick
• Attached to the thickened area (plaque) communication pathway –
in each cell are intermediate filaments especially important in the
• Between the two membrane spread of depolarization in
thickenings, cadherins and several other smooth and cardiac muscle
transmembrane proteins present cells
 Gap junctions • Comprises two apposed hexameric • Found in virtually all • Keep cells polarized
structures called connexons mammalian cells except • Prevent movement of
• One connexon contributed by each cell adult skeletal muscle and materials between the cells
• Create a gap of ~3 nm between the two erythrocytes
cell membranes • Abundant in cardiac and
smooth muscles

Hemidesmosomes • Look like half-desmosomes that attach cells to the underlying basement membrane
• Connected intracellularly to intermediate filaments
• Contain integrins rather than cadherins (unlike desmosomes)
Focal adhesions • Large, dynamic, (integrin-dependent) protein complexes through which the actin cytoskeleton of a cell
connects to the ECM
• Attach cells to their basal laminas

Study Sources:

1. Chapter 3, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
2. Chapter 2, Ganong’s Review of Medical Physiology, 26th edition
3. The Extracellular Matrix - Chapter 16, Guyton and Hall Textbook of Medical Physiology, 14th edition
4. Molecular Biology of the Cell. 4th edition - https://www.ncbi.nlm.nih.gov/books/NBK26937/
5. Human Physiology An Integrated Approach, Dee Silverthorn, 8th edition