2/4 Lecture

Discussion of cytoskeleton and its significance in cell structure and interaction.
Importance of building a mental framework about cell processes and interactions.
- Overview of cellular structures:
Cytoskeleton: The foundational structures.
Importance of proteins and membranes in cell communication.
Consideration of the extracellular matrix and its role in environmental interaction.
- Key themes:
Understanding how the components come together to give cells their shape and function.
The dynamic nature of cell interactions and organization.

Study guide includes a blank illustration of the cell with compartments and membranes labeled.
High-resolution version available for interactive study on tablets or for printing.
- Encouragement to study processes individually but relate back to understand the overall picture of cellular operation.

Start with actin in the cytoskeletal discussion.
- Relation of actin structure to protein interactions.
Overview of three major components:
- Microtubules: Green in microscopy illustrations.
- Actin Filaments: Red in illustrations, also known as microfilaments.
- Intermediate Filaments: Blue in illustrations.
Commonality between actin and microtubules:
- Both are dynamic with motor proteins.
- Intermediate filaments are more stable/static.

Definition:
- Actin Filaments (Microfilaments): Helical polymers, flexible, 8 nanometers in diameter.
Functions in diverse configurations, such as microvilli and muscle contraction.
- Actin Structure:
Composed of globular actin (G-actin), specifically the same identical subunit repeated.
Features binding pockets for ATP central to the subunit.
Differences are made between the plus and minus ends of actin filaments.
- Polymerization:
G-actin assembles into F-actin (Filamentous Actin).
Requires ATP for assembly.
Nucleation phase: - Three actin subunits must collocate to initiate filament growth.
Post-nucleation, filament elongation occurs rapidly.
Steady state occurs when assembly and disassembly rates are balanced.

Definition: Actin filament length remains constant while monomers are added at the plus end and removed from the minus end.
Critical for cellular movement and dynamics.
Treadmilling range: Concentration of actin monomers decides behavior of filaments.
Important role in providing stability and mobility within cells.

**Profilin and Thymosin:
- Profilin**: Promotes assembly of actin filaments.
Thymosin: Inhibits assembly by blocking monomer binding.
- ARP2/3 Complex:
Facilitates actin filament branching, allows for more efficient assembly.
Mimics the plus end of an actin monomer to nucleate new filaments.
- Formins:
Structurally suited to stabilize and enhance assembly at growing filament ends.
Assist in quicker filament assembly alongside profilin.
Forms additional binding sites to further boost filament growth.

Capping proteins can regulate growth/shrinkage from either end.
They stabilize filaments, preventing assembly or disassembly.
- Cofilin’s Role:
Breaks down existing actin filaments, particularly those that are ADP-bound, leading to disassembly.
Introduces over-twist, destabilizing filament structure and facilitating fragmentation.

Actin crosslinking governs how actin filaments are bundled.
Fibrin: Creates tight, parallel bundles, aiding in the structural integrity of cell extensions (i.e., filopodia).
Alpha-Actinin: Creates looser, antiparallel configurations that allow contractile bundles in muscle cells.
Crosslinking maintains organization and versatility in various cellular processes, including cell migration.

In migrating cells, the organization of the actin cytoskeleton is crucial:
- Filopodia: Formed where actin bundles push the membrane forward.
- Lamellipodia: Formed where actin promotes broader membrane extensions to facilitate overall cell movement.
Understanding actin dynamics is vital to grasp the biological mechanics involved in cell behavior and interactions in various contexts.