Lecture 10 - Recording W25

Exam Information

  • Midterm Exam Schedule

    • Exam number two is scheduled for next Thursday.

    • The format will be identical to exam number one.

  • Recitations Changes

    • Thursday, recitations will be canceled.

    • Wednesday all recitation sections are open for drop-in review from 11 AM to 12:20 PM.

  • Exam Number Three

    • Scheduled during finals week on Wednesday from 1 PM to 3 PM.

    • Location to be determined.

Class Focus

  • Conceptual Cumulative Structure

    • Today's class and Thursday's class will review the cell from a broad perspective, connecting previous concepts.

  • Topics

    • Cell Migration: Understanding how cells move in the right direction through various processes.

    • Cell Division: Overview of the cell cycle and its regulatory mechanisms.

Importance of Cell Migration and Proliferation

  • Critical for developmental processes including:

    • Cardiac cell migration to the heart's location.

    • General cell movement during organismal development.

  • Examples of Cell Motility

    • Growth cones from embryonic rat brain searching for synaptic connections.

    • Movement in immune cells, such as killer T cells targeting cancer or infected cells.

  • Research Example

    • Injection of human fibroblasts into a live rat's salivary gland showcasing the immune response.

Cell Migration Mechanisms

  • Mesenchymal Cell Migration

    • Defines migration of fibroblasts as adherent cells moving as single entities.

    • Different from amoeboid migration, which is faster due to lower adhesion.

  • Key Components of Migration

    • Lamellipodium Formation: Driven by small GTPase RAC1 and ARP2/3 complex facilitating actin polymerization.

    • Blebs: Pressure-based protrusions that do not rely on actin polymerization.

    • Adhesion Formation: Requires integrins connecting to the extracellular matrix for adhesion stability.

Stages of Cell Migration

  1. Attachment

    • Cells bind to the surface via integrins connecting to the extracellular matrix.

  2. Flattening

    • Combination of adhesion and contractility helps cells spread.

  3. Polarization

    • Microtubules orient the cell and enable directional movement.

  4. Protrusion Generation

    • Typically involves lamellipodial protrusions pushing the cell membrane forward.

  5. New Adhesion Formation

    • New connections at the leading edge while breaking old contacts at the trailing edge.

  6. Directional Migration

    • Involves chemotaxis in response to guidance signals.

Key Proteins and Pathways in Migration

  • Integrins: Heterodimers facilitating cell adhesion to the matrix, important in generating traction forces.

  • RAC1 and RHOA

    • RAC1 drives lamellipodia formation and protrusion at the front of the cell.

    • RHOA activates contractility, facilitating rear retraction leading to migration.

  • Crosstalk Between RAC1 and RHOA

    • Their signaling pathways regulate protrusion and contraction, determining directionality in migration.

Summary of Cell Movement Types

  • Cells can migrate using different mechanisms:

    • Lamellipodia: Utilizes actin polymerization.

    • Bleb-based Migration: Uses hydrostatic pressure to extend the cell membrane without actin.

    • Immune Response: Cells like neutrophils demonstrate rapid movement dynamics aiding in immune defense.

Conclusion

  • Future Classes

    • Building on these concepts to explore more details about cell division, migration, and dynamics in living systems.

  • Expect more practical examples and in-depth discussions of migration processes in forthcoming sessions.