04/16/26 Cell Motility and Wound Healing: Mechanisms and Implications

Overview of class agenda and topics to be covered. - Focus on cell motility and wound healing processes. - Final examination logistics provided.
Importance of cell mobility in biological processes.

Definition and Purpose: A wound healing assay is a laboratory technique used to study cell migration. It involves: - Cells are grown in a dish. - A pipette tip is used to create a 'wound' or scratch in the cell monolayer, scraping away cells in that area.
Cell Types Involved: - Various cell types migrate into the created wound: - Immune cells: Clean up potential infections by targeting microbes and foreign antigens. - Repair cells: Replace lost cells and help in healing by depositing new tissues.
Personal example of skin cells moving to heal a burn.

Brief review of previous material (focus on mitosis) before transitioning to cell motility for the following session.
A discussion on the spindle assembly checkpoint (SAC) is to be completed.
Class structure moving forward mentions recent material review and logistic details about the final exam.

Key Concept: The spindle assembly checkpoint (SAC) is crucial for proper mitotic progression.
Mechanisms Discussed: - Chromatid separation mechanisms during anaphase. - The role of redundancy in cellular systems.
Important Proteins: - MAD2: A protein critical for the SAC, discovered as a result of studies aimed at identifying proteins that lead to mitotic arrest. It inhibits prematurely advancing into anaphase until chromatid attachment is confirmed. - BUB3 and BUBR1: Part of the SAC signaling pathway along with MAD2. - CDC20: Influences ubiquitination of cyclin B, facilitating exit from mitosis by targeting regulatory proteins for degradation.

Mechanistic overview during anaphase: - Signaling after Retrieving Tension: Proper attachment of microtubules to kinetochores leads to signal broadcasts to kick off a complex activation. - Securin and Separase: Securin inhibits separase, and degradation of securin through ubiquitination frees separase to cleave cohesin (the protein binding sister chromatids). - These events trigger chromatid separation and are tied to overall chromosome movement.

Kinesin 13 (mCaC): A protein that shortens microtubules from either end, contributing to the physical pulling of chromatids apart during anaphase.
Motor Proteins and Microtubules: Other kinesins modulate the elongation of the cell and facilitate the movement of the two chromosome poles apart from each other to define the cleavage area for cytokinesis. - Role of dynein in moving protein complexes away from kinetochores.

Action of Actin and Myosin: Actin filaments and myosin II are critical for cell pinch during cytokinesis.
Formation of the Contractile Ring: Actin structures form a contractile ring that contributes to cell division. This is regulated through various signaling pathways, including those mediated by small GTPases like Rho A.
Implications of aberrant cytoskeleton organization leading to daughter cells with unequal chromosome segregation.

Definition and Importance: Cell motility includes various processes essential for: - Tissue and organ development. - Wound healing. - Immune response. - Examples of hijacked motility processes in cancer metastasis.

Various cell types promote movement through similar fundamental biological mechanisms.
Cell Protrusions: - The leading edge termed the lamellipodium is key for cell migration, expanding the cell outward.
Protrusive Force: Generated by actin polymerization initiating protrusion, often dictated by Rho-family signaling pathways, leading to reorganization of the mobile structures.
Actin filament dynamics (growth and disassembly) are critical for maintaining a range of cellular movement utilities, including adhering to surfaces.
Adhesion Structures: As the cell moves, it must form and break adhesion points in an orchestrated pattern to facilitate locomotion with new points of attachment.

Role of Cytotoxic T Cells: Actively migrate to locate and kill virally infected or cancerous cells using membranous protrusions and actin-driven forces.

Impacts of cell types such as fibroblasts in response to wounds stem from varied mechanisms of movement requiring coordinated actin dynamics—extending through protrusions at the cell's leading edge and effectively using adhesion capacity for cellular migration.

Chemotaxis: Cell migration in response to molecular signals such as growth factors (EGF and PDGF).
WASP Protein: Critical in activating ARP2/3 complex facilitating actin nucleation and polymerization for cellular movement.

Pathogenic bacteria like listeria utilize the host's cytoskeleton dynamics using actin comet tails for intracellular movement, thus highlighting a unique mechanism of cellular propulsion.

Conclude with a brief overview of cell death pathways (extrinsic versus intrinsic), emphasizing the importance of surrounding stimuli and cellular health.
Understand how these cellular pathways contribute to wider biological processes and potential implications for human health, particularly in contexts like cancer.

The following session will focus on apoptosis, cell death mechanisms, and their regulatory pathways while integrating past knowledge with new insights learned during orientation into cell motility dynamics.