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Cytoskeleton Structure
and Cell Motility

Master the three filament systems that give cells their shape, internal organization, and ability to move: from microfilaments to microtubules.

MCAT Biology

What Is the Cytoskeleton?

The cytoskeleton is a dynamic network of protein filaments that extends throughout the cytoplasm of eukaryotic cells. Unlike a building's skeleton, it is constantly assembled and disassembled, making it remarkably adaptable.

The Three Filament Systems

Microfilaments
Actin polymers, ~7 nm diameter. Thinnest filaments: cell shape, movement, cytokinesis.
Intermediate Filaments
Diverse proteins (keratin, vimentin), ~10 nm. Mechanical strength and anchoring.
Microtubules
\(\alpha/\beta\)-tubulin dimers, ~25 nm. Largest: intracellular transport, mitotic spindle, cilia/flagella.

Filament Size Comparison

Microfilament ~7 nm Actin (G-actin) Intermediate Filament ~10 nm Coiled-coil dimers Microtubule ~25 nm 13 protofilaments \(\alpha\) \(\beta\)

Microfilaments: Actin in Action

G-actin (globular) monomers polymerize into F-actin (filamentous) double helices. Polymerization is ATP-dependent: ATP-actin adds to the (+) end faster than ADP-actin dissociates from the (-) end, creating treadmilling.

Cell Crawling
Actin polymerization at the leading edge pushes the membrane forward (lamellipodia, filopodia).
Cytokinesis
Contractile ring of actin + myosin II pinches the cell in two during division.
Muscle Contraction
Sarcomere thin filaments: actin slides past myosin thick filaments.

Microtubules: Highways of the Cell

Hollow tubes of 13 protofilaments, each composed of \(\alpha\)-tubulin/\(\beta\)-tubulin heterodimers. Polymerization is GTP-dependent: GTP-tubulin adds at the (+) end; hydrolysis to GDP destabilizes, causing dynamic instability (rapid shrinkage = catastrophe, regrowth = rescue).

Intermediate Filaments: Tensile Strength

Unlike actin and tubulin, intermediate filaments (IFs) are not polar and do not bind nucleotides (no ATP/GTP required). They form rope-like coiled-coil dimers that provide mechanical resilience.

1
Keratins: epithelial cells (hair, nails, skin). Types I and II form heterodimers.
2
Vimentin: mesenchymal cells (fibroblasts, white blood cells). Marker for mesenchymal tumors.
3
Neurofilaments: axons of neurons. Provide caliber and strength to long axonal processes.
4
Lamins: line the inner nuclear membrane. Disassembly during mitosis allows nuclear envelope breakdown.

Motor Proteins: Moving Cargo

(-) end (+) end Cargo Kinesin → toward (+) end Cargo Dynein ← toward (-) end Actin filament Myosin: walks toward (+) end of actin

Cilia and Flagella

9+2 Axoneme (cross-section) 9 outer doublets (A + B tubules) central pair Dynein arms

Treadmilling vs Dynamic Instability

Treadmilling (Actin)
Net addition at (+) end and net loss at (-) end occur at roughly equal rates. The filament "moves" through the cytoplasm while maintaining constant length. Driven by ATP hydrolysis.
Dynamic Instability (MTs)
Microtubules alternate between rapid growth and rapid shrinkage (catastrophe). Regrowth is called rescue. Driven by GTP hydrolysis at the (+) end: loss of the GTP cap triggers catastrophe.

Drugs That Target the Cytoskeleton

Drug Target Mechanism Clinical Use
Colchicine Microtubules Prevents polymerization Gout
Taxol (Paclitaxel) Microtubules Prevents depolymerization Cancer
Vincristine Microtubules Prevents polymerization Cancer
Cytochalasin Actin Caps (+) end, blocks polymerization Research tool
Phalloidin Actin Stabilizes F-actin, prevents depolymerization Research tool

Filament Polarity and Organization

Nucleus MTOC (+) (+) (+) (+) (-) Actin cortex at membrane MTs: (-) at MTOC → (+) at periphery

How to Identify the Filament Type

1
Check the function described. Cell movement or cytokinesis? Likely actin (microfilaments). Intracellular transport or mitosis? Likely microtubules. Mechanical strength? Likely intermediate filaments.
2
Look for nucleotide clues. ATP hydrolysis → actin. GTP hydrolysis → microtubules. No nucleotide mentioned → intermediate filaments.
3
Check the protein monomer. Actin (G-actin), \(\alpha/\beta\)-tubulin, keratin/vimentin/lamin/neurofilament proteins.
4
Note the diameter. ~7 nm (microfilaments) < ~10 nm (intermediate) < ~25 nm (microtubules).
5
Consider the motor protein. Myosin on actin. Kinesin/dynein on microtubules. No motor proteins on IFs.

Example: Vesicle Transport

A neurotransmitter-containing vesicle is synthesized in the cell body and must travel down a 1-meter axon to the synaptic terminal. Which motor protein and filament system are involved?

Example: Kartagener Syndrome

A patient presents with recurrent sinusitis, bronchiectasis, and situs inversus (mirror-image organ placement). Sperm motility is also impaired. What is the molecular defect?

Example: Drug Mechanism

A cancer chemotherapy drug is found to arrest cells in metaphase. Treated cells show intact, stabilized mitotic spindles that cannot shorten. Which drug is this most consistent with?

Common Mistakes

✕ Confusing Kinesin and Dynein
Kinesin moves toward (+) end (periphery). Dynein moves toward (-) end (MTOC). Don't reverse them.
✕ Mixing Up Nucleotides
Actin uses ATP. Microtubules use GTP. Intermediate filaments use neither. Motor proteins all use ATP.
✕ Taxol vs Colchicine
Both block mitosis but by opposite mechanisms. Taxol = stabilizes (prevents depolymerization). Colchicine = destabilizes (prevents polymerization).
✕ IFs Have No Polarity
Unlike actin and MTs, intermediate filaments have no (+) or (-) end and no associated motor proteins.
✕ Cilia vs Flagella Structure
Both have the same 9+2 axoneme. The difference is length and number, not internal structure. Don't confuse with 9x3 (basal bodies/centrioles).

Summary Comparison

Feature Microfilaments Intermediate Microtubules
Monomer G-actin Various (keratin, etc.) \(\alpha/\beta\)-tubulin
Diameter ~7 nm ~10 nm ~25 nm
Nucleotide ATP None GTP
Polarity Yes (+/-) No Yes (+/-)
Motors Myosin None Kinesin, Dynein
Dynamics Treadmilling Stable Dynamic instability
Key Roles Shape, motility, cytokinesis Mechanical strength Transport, mitosis, cilia

Question 1 of 5

A cell biologist treats fibroblasts with cytochalasin D. Which cellular process would be most directly inhibited?

Question 2 of 5

Which motor protein transports vesicles from the Golgi apparatus toward the (+) end of microtubules at the cell periphery?

Question 3 of 5

A researcher observes that a drug causes microtubules to remain polymerized and resistant to depolymerization, arresting cells in metaphase. This drug is most likely:

Question 4 of 5

A patient with Kartagener syndrome has defective dynein arms in axonemal structures. Which of the following would NOT be expected as a clinical finding?

Question 5 of 5

During mitosis, the nuclear envelope breaks down. Which cytoskeletal component must be depolymerized for this to occur?