🦠Cell Biology Unit 7 – Cytoskeleton and Cell Motility

Key Components of the Cytoskeleton

• Consists of three main protein filaments: microfilaments, microtubules, and intermediate filaments
• Provides structural support and maintains cell shape
• Enables cell movement and intracellular transport
• Plays a crucial role in cell division, particularly during mitosis and cytokinesis
• Contributes to the organization and distribution of organelles within the cell
• Facilitates cell-cell and cell-matrix interactions
• Allows cells to respond to mechanical stimuli and changes in their environment
• Undergoes dynamic remodeling to adapt to cellular needs

Structure and Function of Microfilaments

• Composed of actin monomers that polymerize to form thin, flexible filaments (6-8 nm in diameter)
• Exhibit polarity with a plus (barbed) end and a minus (pointed) end
• Plus end undergoes rapid polymerization while the minus end experiences slower depolymerization
• Actin filaments organize into higher-order structures such as bundles and networks
  • Bundles provide structural support and enable the formation of cellular protrusions (filopodia and microvilli)
  • Networks facilitate cell movement and shape changes (lamellipodia)
• Involved in muscle contraction through interaction with myosin motor proteins
• Play a key role in cytokinesis during cell division by forming the contractile ring
• Contribute to cell-cell adhesion and cell-matrix interactions through association with adhesion complexes (focal adhesions and adherens junctions)

Structure and Function of Microtubules

• Consist of α-tubulin and β-tubulin heterodimers that assemble into hollow, cylindrical filaments (25 nm in diameter)
• Exhibit polarity with a plus end (β-tubulin exposed) and a minus end (α-tubulin exposed)
• Plus end undergoes dynamic instability, alternating between periods of growth and rapid shrinkage
• Minus end is typically anchored to the centrosome, which serves as the microtubule-organizing center (MTOC)
• Provide structural support and maintain cell shape, particularly in elongated cells (neurons)
• Serve as tracks for intracellular transport of organelles, vesicles, and macromolecules
  • Kinesin motor proteins move cargo towards the plus end
  • Dynein motor proteins move cargo towards the minus end
• Form the mitotic spindle during cell division, ensuring proper chromosome segregation
• Contribute to the formation and maintenance of cilia and flagella, enabling cell motility and fluid movement

Structure and Function of Intermediate Filaments

• Composed of a diverse family of proteins, including keratins, vimentins, and lamins
• Assemble into rope-like filaments (10 nm in diameter) that are more stable and less dynamic than microfilaments and microtubules
• Provide mechanical strength and resistance to mechanical stress
• Contribute to the structural integrity of the nuclear lamina, which supports the nuclear envelope
• Play a role in anchoring organelles and maintaining their spatial distribution within the cell
• Participate in cell-cell and cell-matrix adhesion through association with desmosomes and hemidesmosomes
• Involved in signal transduction and cellular responses to mechanical stimuli
• Mutations in intermediate filament proteins can lead to various genetic disorders (epidermolysis bullosa simplex)

Cytoskeleton Dynamics and Regulation

• Cytoskeletal filaments undergo constant assembly and disassembly, allowing for dynamic remodeling
• Actin polymerization is regulated by various actin-binding proteins (profilin, cofilin, and Arp2/3 complex)
  • Profilin promotes actin polymerization by facilitating the exchange of ADP for ATP on actin monomers
  • Cofilin severs and depolymerizes actin filaments, increasing the pool of available actin monomers
  • Arp2/3 complex nucleates the formation of new actin filaments and promotes branching
• Microtubule dynamics are influenced by microtubule-associated proteins (MAPs) and motor proteins
  • MAPs (tau and MAP2) stabilize microtubules and regulate their interactions with other cellular components
  • Motor proteins (kinesin and dynein) generate force and movement along microtubules
• Rho GTPases (Rho, Rac, and Cdc42) are key regulators of cytoskeletal dynamics and cell motility
  • Rho promotes the formation of stress fibers and focal adhesions
  • Rac stimulates the formation of lamellipodia and membrane ruffles
  • Cdc42 induces the formation of filopodia and regulates cell polarity
• Post-translational modifications (phosphorylation and acetylation) modulate the properties and interactions of cytoskeletal proteins

Cell Motility Mechanisms

• Amoeboid movement involves the extension of pseudopodia and the contraction of the cell body
  • Driven by the coordinated assembly and disassembly of actin filaments
  • Requires the activity of myosin motor proteins for contraction and retraction
• Mesenchymal movement is characterized by the formation of lamellipodia and filopodia at the leading edge
  • Actin polymerization pushes the plasma membrane forward, creating protrusions
  • Adhesion complexes (focal adhesions) form at the leading edge, providing traction
  • Contraction of actin-myosin bundles generates tension and promotes forward movement
• Collective cell migration occurs when groups of cells move together while maintaining cell-cell contacts
  • Observed during embryonic development, wound healing, and cancer invasion
  • Involves the coordination of cytoskeletal dynamics and cell-cell adhesion molecules (cadherins)
• Cilia and flagella enable the movement of individual cells or the propulsion of fluids across cell surfaces
  • Consist of microtubule-based structures called axonemes
  • Dynein motor proteins generate the sliding movement of microtubules, resulting in bending and beating motions

Cellular Processes Involving the Cytoskeleton

• Cell division relies on the cytoskeleton for chromosome segregation and cytokinesis
  • Microtubules form the mitotic spindle, which captures and aligns chromosomes
  • Actin filaments and myosin motor proteins form the contractile ring, which divides the cell into two daughter cells
• Intracellular transport of organelles, vesicles, and macromolecules depends on the cytoskeleton
  • Microtubules serve as tracks for long-distance transport
  • Actin filaments facilitate short-range transport and anchoring of organelles
• Cell signaling and signal transduction involve cytoskeletal components
  • Actin filaments and microtubules participate in the trafficking and localization of signaling molecules
  • Cytoskeletal rearrangements can be triggered by extracellular signals (growth factors and hormones)
• Cellular polarity and asymmetric cell division rely on the asymmetric distribution of cytoskeletal elements
  • Microtubules and actin filaments establish and maintain cell polarity
  • Asymmetric segregation of cell fate determinants during cell division is mediated by the cytoskeleton

Clinical and Research Applications

• Cytoskeletal disorders can arise from mutations in genes encoding cytoskeletal proteins
  • Mutations in actin or actin-binding proteins can cause muscular dystrophies and cardiomyopathies
  • Defects in microtubule-associated proteins (tau) are linked to neurodegenerative diseases (Alzheimer's disease)
• Cytoskeletal targeting drugs are used in cancer therapy to disrupt cell division and migration
  • Microtubule-targeting agents (taxanes and vinca alkaloids) inhibit mitotic spindle formation
  • Actin-targeting agents (cytochalasins) disrupt actin polymerization and cell motility
• Cytoskeletal research has implications for tissue engineering and regenerative medicine
  • Understanding cytoskeletal dynamics can guide the development of scaffolds and biomaterials that promote cell migration and tissue regeneration
• Live-cell imaging techniques (fluorescence microscopy) allow the visualization of cytoskeletal dynamics in real-time
  • Fluorescent labeling of cytoskeletal proteins (GFP-actin and GFP-tubulin) enables the tracking of filament assembly and disassembly
  • Super-resolution microscopy (STORM and PALM) provides unprecedented detail of cytoskeletal structures and interactions