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Cell Biology Unit 9: Cell Junctions, Adhesion and the Extracellular Matrix
This unit explains how cells stick to one another and to the extracellular matrix, how junctions seal, strengthen and connect tissues, and how the matrix itself is built and sensed.
Covers: Tight junctions and epithelial polarity, Adherens junctions and cadherins, Desmosomes and hemidesmosomes, Gap junctions and plasmodesmata, Integrins and focal adhesions, Collagen, basal lamina and other ECM proteins, Proteoglycans, matrix remodeling and mechanotransduction
Study guide
Animal cells in tissues are held together by junctions with distinct jobs. Tight junctions, made of claudin and occludin strands near the apical surface of epithelia, seal the space between cells so solutes cannot leak through the paracellular route. They also act as a fence that keeps apical and basolateral membrane proteins apart, which lets epithelia transport materials in one direction. Leaky tight junctions lower transepithelial electrical resistance and let drugs, ions and pathogens slip between cells.
Anchoring junctions resist mechanical stress. Adherens junctions use classical cadherins such as E-cadherin, which bind identical cadherins on neighboring cells only when Ca²⁺ is present. Inside, β-catenin and α-catenin link them to a belt of actin filaments. Desmosomes use desmosomal cadherins (desmogleins and desmocollins) linked through plakoglobin and desmoplakin to keratin intermediate filaments, tying the keratin networks of cells into a tissue-wide web. Hemidesmosomes use integrin α6β4 to anchor basal cells to laminin in the basal lamina, also linked to keratin. Defects in these junctions, as in pemphigus or epidermolysis bullosa, cause blistering.
Communicating junctions connect cytoplasms. In vertebrates, gap junctions are made of connexins: six form a connexon, and two connexons from adjacent cells dock to form a channel about 1.5 nm wide that passes ions and molecules under about 1 kDa, such as cAMP, ATP and Ca²⁺. Gap junctions couple heart and smooth muscle cells electrically and coordinate tissue responses; they close when Ca²⁺ rises or pH falls, isolating damaged cells. Plant cells instead use plasmodesmata, membrane-lined channels through the cell wall that link cytoplasms and contain a strand of ER.
Cells attach to the extracellular matrix through integrins, αβ heterodimers whose extracellular heads bind ECM proteins (many through the RGD motif of fibronectin) and whose tails bind talin, vinculin and other adaptors linked to actin at focal adhesions. Integrins signal both ways: inside-out signaling through talin and kindlin switches them to high affinity, and outside-in signaling through kinases such as FAK controls survival, growth and movement. Leukocytes use selectins to roll on blood vessels and activated integrins binding ICAM-1 (an IgCAM) to stop and exit. Cells also sense matrix stiffness through integrin adhesions, a process called mechanotransduction.
The ECM is secreted by cells, mostly fibroblasts in connective tissue. Collagen, the most abundant animal protein, is a triple helix of chains with a Gly-X-Y repeat rich in proline and hydroxyproline; vitamin C is required for the hydroxylation that stabilizes it, and glycine substitutions cause osteogenesis imperfecta. Fibrillar collagens (type I) resist tension, while type IV collagen and laminin form the basal lamina. Elastin gives tissues stretch and recoil, and fibronectin links cells to matrix. Proteoglycans carry negatively charged glycosaminoglycans that attract water and resist compression. Matrix metalloproteinases remodel the ECM during development and wound healing and help cancer cells invade.
Key ideas
- Tight junctions form a barrier between cells and a fence between membrane domains.
- Adherens junctions (cadherins, actin) and desmosomes (cadherins, keratin) hold cells together.
- Hemidesmosomes and focal adhesions use integrins to attach cells to the matrix.
- Gap junctions and plasmodesmata let small molecules pass directly between cells.
- Integrins signal in both directions and sense matrix stiffness.
- Collagen's Gly-X-Y triple helix gives tensile strength, and GAG gels resist compression.
- MMPs remodel the matrix, and their activity contributes to invasion in cancer.
Formulas and rules
Common mistakes
- Mixing up desmosomes (keratin) and adherens junctions (actin).
- Thinking integrins mediate cell–cell adhesion in epithelia; cadherins do that, while integrins mainly bind matrix.
- Believing gap junctions pass proteins; they pass only small molecules under about 1 kDa.
- Forgetting that cadherins require Ca²⁺.
- Confusing hemidesmosomes (cell to basal lamina) with desmosomes (cell to cell).
Before the test, make sure you can
- Identify each junction type by its proteins, partners and cytoskeletal link.
- Explain the barrier and fence functions of tight junctions.
- Predict the effects of removing Ca²⁺ or blocking cadherins, desmogleins or connexins.
- Describe gap junction size limits, regulation and roles in heart muscle.
- Explain integrin binding, inside-out and outside-in signaling, and leukocyte adhesion.
- Describe collagen structure, the role of vitamin C and dominant-negative collagen mutations.
- Explain how proteoglycans, elastin, fibronectin and laminin contribute to the ECM.
- Explain how MMPs and E-cadherin loss contribute to cancer invasion.
Words to know
- Tight junction
- A seal of claudin and occludin strands that blocks paracellular leak and separates membrane domains.
- Claudin
- The main transmembrane protein forming tight junction strands.
- Adherens junction
- A cell–cell junction where cadherins link to actin through catenins.
- Cadherin
- A Ca²⁺-dependent cell–cell adhesion protein that usually binds the same cadherin type.
- β-catenin
- A protein linking cadherins to actin that can also act in Wnt signaling.
- Desmosome
- A button-like cell–cell junction linking keratin filaments through desmosomal cadherins.
- Hemidesmosome
- A junction that anchors epithelial cells to the basal lamina through integrin α6β4 and keratin.
- Gap junction
- A cluster of channels made of connexins that pass ions and small molecules between cells.
- Connexon
- A hemichannel of six connexins in one cell's membrane.
- Plasmodesma
- A membrane-lined channel through the plant cell wall that connects cytoplasms.
- Integrin
- An αβ transmembrane receptor that binds ECM proteins and links to the cytoskeleton.
- Focal adhesion
- An integrin-based site connecting actin stress fibers to the ECM.
- Selectin
- A lectin adhesion protein that mediates leukocyte rolling on blood vessels.
- Collagen
- The main ECM structural protein, a triple helix with a Gly-X-Y repeat.
- Basal lamina
- A thin ECM sheet of type IV collagen and laminin under epithelia.
- Fibronectin
- An ECM glycoprotein with RGD sites that bind integrins.
- Glycosaminoglycan
- A long, negatively charged polysaccharide that attracts water and forms gels.
- Matrix metalloproteinase
- A zinc-dependent protease that degrades ECM proteins.
Sample practice questions
30 more questions like these, from level 1 to 5, are in the practice set.
Which junction seals neighboring epithelial cells so that solutes cannot leak between them?
- Hemidesmosome (basal)
- Gap junction
- Tight junction
- Desmosome
Show the answer and steps
Answer: C) Tight junction
- Tight junctions are formed by strands of claudins and occludin near the apical surface.
- They block the paracellular path between cells.
- Gap junctions let small molecules pass between cells, and desmosomes provide strength.
Cadherins are cell adhesion proteins that require which ion to bind each other?
- K⁺
- Na⁺
- HCO₃⁻
- Ca²⁺
Show the answer and steps
Answer: D) Ca²⁺
- The name cadherin comes from 'calcium-dependent adhesion'.
- Ca²⁺ binds between extracellular domains and makes them rigid enough to bind partners.
- Removing Ca²⁺ with EDTA makes cells round up and detach from each other.
Cultured epithelial cells are placed in a medium containing EDTA, which binds Ca²⁺. What happens and why?
- The cells immediately undergo apoptosis because caspases need Ca²⁺
- Cells detach, because cadherins lose their adhesive shape without Ca²⁺
- Cells bind each other more tightly, because integrins on their lateral surfaces are activated by EDTA
- Gap junctions widen to let proteins through
Show the answer and steps
Answer: B) Cells detach, because cadherins lose their adhesive shape without Ca²⁺
- E-cadherin needs Ca²⁺ bound between its extracellular domains to stay rigid.
- Without Ca²⁺, cadherins become floppy and are cut easily by proteases.
- Adherens junctions and desmosomes fall apart, so the cells separate; this is why EDTA is used to dissociate tissues.