Cytoskeleton and cellular mechanics + fuelling the cytoskeleton

Cellular Movement and the Cytoskeleton: Integrated Explanation

The cytoskeleton is a dynamic network of protein filaments essential for maintaining cell shape, enabling movement, facilitating intracellular transport, and organizing the position of organelles. It is composed of three interconnected components: microtubules, microfilaments (actin filaments), and intermediate filaments, each contributing uniquely to cellular structure and function.

1. Cytoskeleton Components: Overview and Functions

• Microtubules:

• Structure: Hollow, cylindrical tubes composed of tubulin dimers (alpha and beta subunits).

• Function: Act as “tracks” for motor proteins like kinesin and dynein, enabling the transport of vesicles, organelles, and chromosomes.

• Location: Nucleated near the centrosome at the cell center and radiate outward toward the plasma membrane.

• Energy: Polymerization requires GTP hydrolysis, making microtubules highly dynamic, constantly assembling and disassembling.

• Microfilaments (Actin Filaments):

• Structure: Thin, double-stranded helical filaments composed of actin.

• Function: Found beneath the plasma membrane, actin filaments provide mechanical support, enable shape changes, and facilitate movement via interactions with myosin motor proteins.

• Energy: Polymerization and depolymerization are powered by ATP hydrolysis.

• Intermediate Filaments:

• Structure: Rope-like fibers composed of various proteins (e.g., keratin in epithelial cells, vimentin in mesenchymal cells, and neurofilaments in neurons).

• Function: Provide mechanical strength and resist stretching, holding the cell together during stress.

• Energy: Do not require ATP or motor proteins for assembly.

2. Fuel Source for Cytoskeleton Assembly

The cytoskeleton depends on high-energy molecules to assemble its structures and enable motor protein activity:

• Microtubules: Use GTP hydrolysis for tubulin dimer addition and disassembly.

• Actin Filaments: Use ATP hydrolysis to add actin monomers at the filament’s barbed end.

• Motor Proteins: Convert chemical energy (ATP) into mechanical work, powering movement along microtubules and actin filaments.

3. Motor Proteins and Intracellular Transport

Motor proteins use cytoskeletal “tracks” for directional movement:

• Kinesin:

• Moves cargo toward the plus end of microtubules (periphery).

• Structure: A dimer with “feet” that “walk” along the microtubule. Each step requires ATP hydrolysis.

• Dynein:

• Moves cargo toward the minus end of microtubules (center).

• Faster than kinesin, dynein uses a twisting “power stroke” for movement.

• Myosin:

• Interacts exclusively with actin filaments, not microtubules.

• Myosin II: Found in muscle cells for contraction and non-muscle cells for cytokinesis and stress fiber contraction.

• Myosin V: Involved in intracellular transport of organelles and vesicles along actin filaments.

4. Cytoskeleton in Organelle Positioning

The cytoskeleton determines the spatial organization of organelles within the cell:

• Golgi Apparatus: Positioned near the nucleus by dynein moving along microtubules.

• Endoplasmic Reticulum (ER): Spread toward the plasma membrane by kinesin moving along microtubules.

5. Microtubule Dynamics and Cellular Functions

Microtubules are made of 13 protofilaments arranged in a cylindrical shape.

• Their dynamic instability allows them to assemble and disassemble as needed, which is critical for processes like vesicle transport, organelle positioning, and chromosome segregation during mitosis.

• GFP tagging can visualize microtubule nucleation and growth from the centrosome in real-time.

Cytoskeleton in Specific Cellular Contexts

A. Microtubules and Vesicle Transport in Neurons

In neurons, microtubules facilitate the transport of vesicles between the cell body and synapse.

• Kinesin moves vesicles outward to the synapse, while dynein brings them inward.

• Drugs targeting microtubule polymerization (e.g., cancer therapies) disrupt vesicle transport, leading to neuropathies due to impaired neuronal function.

B. Chromosome Segregation in Mitosis

During mitosis, microtubules reorganize into the mitotic spindle, ensuring equal chromosome segregation.

• Errors in spindle formation result in aneuploidy (incorrect chromosome number), often seen in aggressive tumors.

C. Actin Filament Functions and Diversity

Actin filaments are versatile, enabling a wide range of cellular activities:

• Microvilli in epithelial cells increase the surface area for nutrient absorption.

• Stress Fibers in migrating fibroblasts contract to pull the cell forward.

Myosin II and Cell Division:

• During cytokinesis, myosin II contracts actin filaments to form a contractile ring, separating the daughter cells.

Coordination Between Microtubules and Actin:

• Vesicles often travel along microtubules before switching to actin filaments near the cell cortex for delivery to the plasma membrane.

Cytoskeleton in the Immune Response

A. Lymphocyte Homing to a Wound

• Experiment: In a zebrafish larva, lymphocytes exited blood vessels and migrated toward a wound.

• Chemotaxis: Movement was guided by signals from damaged cells and bacteria.

B. Neutrophil Chasing Bacteria

• Neutrophils detect bacterial peptides and use actin-myosin interactions to propel themselves toward the target, exemplifying immune surveillance.

Intermediate Filaments: Structure and Specialization

• Assembly: Intermediate filaments self-assemble into rope-like structures without requiring ATP.

• Function: Provide mechanical strength and resist stretching.

Specialized Neurofilaments:

• Found in neurons, they maintain structural integrity and protect microtubules from damage during bending.