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Cell-Cell Junctions
& Extracellular Matrix

Master the three major junction types, the extracellular matrix, and how cells communicate, adhere, and maintain tissue integrity for the MCAT.

MCAT Biology Foundational Concept 2A

Why Do Cells Need Junctions?

In multicellular organisms, cells don't work in isolation. They must physically connect, communicate, and coordinate to form functional tissues. Cell junctions are specialized protein complexes that accomplish these tasks.

The Three Major Junction Types

Tight Junctions
Seal cells together, preventing paracellular leakage between them
Desmosomes
Anchor cells together mechanically via intermediate filaments
Gap Junctions
Connect cytoplasms of adjacent cells for direct communication

Tight Junctions: The Seal

Cell 1 Cell 2 Claudins Occludins Paracellular space sealed blocked Cytoplasm Cytoplasm

Desmosomes: The Anchor

Cell 1 Cell 2 Dense plaque Cadherins Keratin Keratin Mechanical strength via intermediate filaments

Gap Junctions: The Tunnel

Cell 1 Cell 2 Connexons (6 connexins each) Ions, small molecules Direct cytoplasm-to-cytoplasm transfer

Anchoring to the Basement Membrane

Hemidesmosomes
Anchor a cell to the basal lamina (not to another cell). Use integrins instead of cadherins. Connect to intermediate filaments inside the cell.
Focal Adhesions
Also use integrins to connect cells to ECM. Link to actin filaments (not intermediate filaments). Important for cell migration and signaling.

The Extracellular Matrix

The ECM is the non-cellular structural scaffold surrounding cells. It provides physical support, biochemical signals, and a medium for cell migration. Its composition varies by tissue type.

Collagen Fibers Proteoglycan Fibronectin Cell Integrins

ECM Key Components

Collagen
Most abundant protein in the body. Triple helix of glycine-X-Y repeats. Provides tensile strength.
Proteoglycans
Core protein + GAG chains (e.g., chondroitin sulfate). Highly hydrated: resist compression.
Fibronectin
Glycoprotein linking cells to ECM. Binds both integrins and collagen. Key for cell migration.

Cadherins vs Integrins

Cadherins Integrins
Connection Type Cell-to-cell Cell-to-ECM
Calcium Dependent? Yes Yes (divalent cations)
Found In Desmosomes, adherens junctions Hemidesmosomes, focal adhesions
Intracellular Link Intermediate filaments or actin Intermediate filaments or actin
Signaling Role Contact inhibition Bidirectional (inside-out, outside-in)

How to Identify a Junction Type

1
What connects? Cell-to-cell or cell-to-ECM? If ECM: think integrins (hemidesmosome/focal adhesion).
2
What function? Sealing = tight junction. Anchoring = desmosome. Communication = gap junction.
3
Which proteins? Claudin/occludin = tight. Cadherin = desmosome. Connexin = gap.
4
Which cytoskeletal element? Intermediate filaments = desmosome/hemidesmosome. Actin = adherens/focal adhesion.

Example: Intestinal Epithelium

Apical (lumen) side Tight junction Adherens Desmosome Gap junction Basal (basement membrane) side Hemidesmosomes (integrins)

Example: Cardiac Intercalated Discs

Intercalated discs connect cardiac myocytes end-to-end and contain all three junction types in one structure:

Desmosomes
Prevent cells from being pulled apart during contraction
Gap Junctions
Allow rapid ion flow for synchronized contraction (functional syncytium)
Adherens (Fascia Adherens)
Anchor actin filaments between cells, transmitting contractile force

Example: ECM in Disease

ECM dysfunction underlies several MCAT-relevant pathologies:

1
Scurvy: Vitamin C deficiency impairs collagen hydroxylation (\( \text{Pro} \to \text{Hyp} \), \( \text{Lys} \to \text{Hyl} \)). Collagen cannot form stable triple helices, leading to bleeding gums and fragile blood vessels.
2
Ehlers-Danlos Syndrome: Genetic defects in collagen synthesis cause hyperelastic skin and hypermobile joints.
3
Marfan Syndrome: Mutation in fibrillin-1 (a glycoprotein in elastic fibers) weakens connective tissue, especially in the aorta.
4
Cancer Metastasis: Tumor cells secrete matrix metalloproteinases (MMPs) to degrade ECM and invade surrounding tissues.

Common Mistakes

Confusing Desmosomes and Hemidesmosomes
Desmosomes link cell-to-cell (cadherins). Hemidesmosomes link cell-to-ECM (integrins). "Hemi" = half: only one cell is involved.
Mixing Up Gap and Tight Junctions
Tight junctions seal (block passage). Gap junctions open (allow passage). They do opposite things despite both spanning the intercellular space.
Forgetting Calcium Dependence
Cadherins require \( \text{Ca}^{2+} \). Removing calcium with EDTA disrupts cell-cell adhesion. This is a classic MCAT experimental setup.

Master Summary Table

Junction Protein Function Example
Tight Claudins, occludins Seal Intestine, BBB
Desmosome Cadherins (desmoglein) Anchor (cell-cell) Skin, heart
Gap Connexins Communicate Heart, smooth muscle
Hemidesmosome Integrins Anchor (cell-ECM) Epithelium base
Adherens Cadherins (E-cadherin) Anchor + signal Epithelia, heart

Question 1 of 5

A researcher treats epithelial cells with EDTA, a calcium chelator. Which junction type would be most directly disrupted?

Question 2 of 5

Cardiac muscle cells form a functional syncytium. Which junction type is most responsible for this property?

Question 3 of 5

A patient with scurvy has defective collagen. Which post-translational modification is impaired?

Question 4 of 5

Which ECM component binds integrins on the cell surface and also binds collagen, acting as a bridge between the cell and the structural matrix?

Question 5 of 5

A cell is anchored to the basal lamina via intermediate filaments connected to transmembrane proteins. Which structure is described?