CELL 201 Motility and contraction

What is motility?

driven by motor proteins interacting with the cytoskeleton.

What is contractility?

involving the shortening of muscle cells, powered by myosin interacting with microfilaments (actin).

What are motor proteins, and how do they work?

Convert ATP energy into physical movement.

What is the function of microtubules in motility?

Provide rigid tracks for intracellular transport, has different motor proteins moving in opposite directions (polarity established by MTOC)

What are the two main microtubule motor proteins?

✔ Dyneins → Move toward the minus (-) end (retrograde transport).
✔ Kinesins → Move toward the plus (+) end (anterograde transport).

Microvili vs cilia?

1. increases SA, actin based, no movement

2. move fluids over a surface, MT baed (dyenin)

What is an axoneme?

Microtubule-based structure inside cilia & flagella, anchored at basal bodies providing support and enabling movement

What are the two types of axonemes?

✔ Ciliary axoneme → 9+0 structure (9 outer doublets, no central pair).
✔ Flagellar axoneme → 9+2 structure (9 outer doublets, 2 central MTs).

• A tubule → Complete MT with dynein arms.

• B tubule → Incomplete MT.

How do axonemes generate movement?

Dynein moves along tubulin doublets, causing the structure to bend.

1. Dynein attaches to outer tubulin doublets.

2. ATP hydrolysis allows dynein to move to next spot

3. Returns to original position, causing a slight movement of the whole structure.

Why is axonal transport necessary?

Diffusion is too slow → Motor proteins transport vesicles & organelles along MTs.

What is kinesin

MT motor protein

Kinesin-1 is a heterotetramer with:
✔ 2 heavy chains (bind ATP & drive movement)
✔ 2 light chains (bind cargo)

How does kinesin walk?

🔄 Step-wise movement cycle:

1. Leading head binds ATP → Conformational change.

2. Trailing head swings forward ("power stroke").

3. ADP is released, binding strongly to the microtubule.

4. Trailing head hydrolyzes ATP → Releases Pi → Detaches.
   ✔ Uses 1 ATP per cycle!

How do microfilaments (actin) contribute to motility?

Key for muscle contraction & cell crawling (lamellipodia, filopodia). Requires opposing forces for contraction & movement.

How do crawling cells move (generate force)?

Actin polymerization at the leading edge drives movement.

🔄 Steps of crawling:

1. Extended protrusions (lamellipodia, filopodia).

2. New adhesions form, anchoring actin to the surface.

3. Retrograde actin flow moves MFs backward.

4. Rearward cell contraction pulls the cell forward.

✔ Integrins → Transmembrane proteins that anchor the cell to the extracellular matrix (ECM).

What is chemotaxis?

Directional movement in response to a graded stimulus (e.g., chemical signals).

✔ Chemoattractants → Cells move toward higher concentration (strong actin polymerization).
✔ Chemorepellants → Cells move away from high concentration (weak signal → retraction).

Characteristic of skeletal muscle

• striated

• multinucleated

• voluntary (somatic NS)

• fast, powerful contractions

Characteristic of cardiac muscle

• striated

• mononucleated

• involuntary (autonomic NS)

• intercalated discs and gap junctions for electrical coupling

Characteristic of smooth muscle

• non striated

• mononucleated

• involuntary (autonomic NS)

• slow, long duration, sustained contractions

How does smooth muscle contract?

Triggered by Ca²⁺ influx & activation of myosin light chain kinase (MLCK).

1. Nerve/hormonal signal → Ca²⁺ influx.

2. Ca²⁺ activates calmodulin.

3. Calmodulin activates MLCK.

4. MLCK phosphorylates myosin light chains → Myosin can walk on actin.

5. When Ca²⁺ falls, MLCK dephosphorylates myosin → Muscle relaxes.

How does myosin move along microfilaments? What do all myosins contain?

Myosin moves in one direction along actin filaments.

• 1 heavy chain (polypeptide).

• Globular head group.

• Tail region.

Myosins vs kinesins?

both + end transport, BUT

1. MF, muscle contractions, operate in large groups, move short distances

2. MT, vesicle transport/mitosis, operate small groups, move long distances

What are myofibrils?

Bundles of thin & thick filaments arranged in repeating units called sarcomeres.

What are the components of myofibrils?

✔ Thick filaments → Myosin II
✔ Thin filaments → Actin, Tropomyosin, Troponin (TnT, TnI, TnC)

Hierarchy of muscle structure (largest to smallest)?

Muscle (organ) → Muscle fiber/cell → Myofibrils → Thin & thick filaments → Actin & Myosin proteins

What is a sarcomere?

The fundamental contractile unit of muscle, giving it a striated appearance.

What defines the length of a sarcomere?

One Z-line to the next Z-line.

What is the sarcoplasmic reticulum (SR)?

Ca²⁺ storage & release site, surrounds myofibrils with T-tubules.

How does Ca²⁺ regulate muscle contraction?

✔ Low Ca²⁺ → Troponin blocks myosin-binding sites (relaxed).
✔ High Ca²⁺ → Ca²⁺ binds to troponin C (TnC) → Troponin changes shape → Tropomyosin moves → Myosin binds actin → Contraction.

What is CapZ

Stabilizes the + end of actin.

What is tropomodulin

Binds to the - end of actin to maintain length.

What is the structure of a thick filament

form a staggered array.

✔ Globular head → Binds to actin & hydrolyzes ATP.
✔ Hinge region → Allows power stroke movement.
✔ Tail region → Forms the filament backbone.

What is titin

Links thick filament to Z-line, keeping it aligned.

What is myomesin?

Anchors thick filaments to the M-line.

What is tropomyosin?

Blocks myosin-binding sites at rest.

What is Troponin Complex

• TnT → Attaches tropomyosin.

• TnC → Binds Ca²⁺.

• TnI → Inhibits myosin binding at rest.

regulates myosin interactions

What is nebulin?

Helps anchor thin filaments to the Z-disk.

What is α-Actinin?

Attaches actin to Z-disk, determining sarcomere length.

What happens during muscle contraction?

1. ATP binds to myosin head → Myosin releases actin (relaxed state).

2. ATP hydrolyzes (ADP + Pi) → Myosin "cocks" into a ready position.

3. Myosin head binds to actin → Cross-bridge forms.

4. Pi is released → Myosin pulls actin toward M-line (power stroke, contraction).

5. ADP is released, and a new ATP binds → Myosin detaches, cycle repeats.

✔ Requires ATP hydrolysis & Ca²⁺ binding to troponin!

What protein controls Ca²⁺ release from the SR?

Ryanodine receptor (RyR) → Ca²⁺ channel in the SR membrane.

Electrical stimulus → RyR opens → Ca²⁺ floods into cytoplasm → Muscle contracts.

How is Ca²⁺ removed to stop contraction?

Ca²⁺ ATPase pumps Ca²⁺ back into SR, allowing troponin to block myosin-binding sites → Muscle relaxes.

How does an action potential (AP) trigger muscle contraction?

1. AP arrives at the NMJ → Triggers release of ACh (neurotransmitter).

2. Voltage-gated Ca²⁺ channels open → Ca²⁺ released from SR.

3. Ca²⁺ binds troponin → Tropomyosin shifts → Myosin can bind actin.

4. Thin & thick filaments slide past each other → Muscle contracts.

5. Ca²⁺ is pumped back into SR by Ca²⁺ ATPase → Contraction stops.