Multicellularity and Cell Adhesion

CBIO3400 Lecture Notes: L20B - Multicellularity and Cell Adhesion

Date:

• 04/06/2026

Learning Objectives:

• Differentiate between unicellular and multicellular organisms.
• Understand the importance of cell contacts in multicellular organisms.
• Learn about the roles of Integrins and Cadherins in cell adhesion.
• In-Class Activity (3 points).

Single Cells and Multicellularity:

• Single Cells:
  • Undifferentiated: Cells that have not yet developed into specialized cell types.
  • Differentiated: Cells that have developed distinct structures and functions.
  • Examples:
  • Filamentous Cells
  • Hyphae
  • Magnetotactic bacteria

Life Cycle of Dictyostelium discoideum:

• Stages:
  • Growth: 6-10 hours
  • Aggregation: 10-14 hours
  • Slug Formation: 14-18 hours
  • Culmination and Fruiting Body Formation: 18-24 hours.
• Key Points:
  • Mature fruiting body and slug formation highlight the cellular interactions in multicellularity.
  • Development involves phases marked by specific time durations.

Mechanisms Necessary for Functional Multicellularity:

• Cell Proliferation: The process by which cells multiply.
• Cell Differentiation: The process where cells become specialized in structure and function.
• Cell Morphogenesis: The process that causes cells to change shape.

Evolution of Multicellular Organisms:

• Hypothesis of Evolution:
  • Individual unicellular organisms aggregate to form pluricellular and eventually multicellular organisms.
  • Evolutionary Example: Unicellular flagellated protists aggregate, leading to specialized reproductive cells and subsequent tissue formation.

Experimental Evidence of Cell Adhesion:

• Townes and Holtfreter Experiment (1955):

• Cells from different germ layers do not mix, indicating intrinsic cell adhesion properties.

• Definition: A network of proteins and polysaccharides in the space between cells that provides structural support, regulates cell behavior, and facilitates communication.
• Components of ECM:
  • Adhesion Proteins: Proteins that help bind cells to the matrix.
  • Structural Proteins: Provide physical support and structure.
  • Proteoglycans: Large molecules composed of a protein core and glycosaminoglycan (GAG) chains.
• Key Macromolecules in ECM:
  • Proteoglycans: Including hyaluronan, perlecan, decorin, aggrecan.
  • Fibrous Proteins: Including type IV collagen and fibronectin.

Cell Adhesion Molecules (CAMs):

• Definition: Transmembrane proteins that mediate cell adhesion in multicellular organisms.
• Structure:
  • A small intracellular domain.
  • A transmembrane domain.
  • A large extracellular domain.
• Types: Can be Ca2+-dependent or Ca2+-independent.
• Homophilic vs. Heterophilic Interactions: CAMs can interact with the same type (homophilic) or different types (heterophilic) of CAMs on other cells or the ECM.

Integrins:

• Function: Link cells to the ECM and are involved in a variety of cell signaling processes.

• Major Activity States:

  • Inactive (Folded): Conformational state when integrins are not engaged.
  • Active (Extended): Conformational state when integrins bind ligands in the ECM.

• Ligands:

  • Fibronectin
  • Collagen
  • Laminin.
  • Adaptor proteins include talin, kindlins, and RIAM.

• Importance of Integrins:

  • Loss of integrins can disrupt tissue organization and function.
  • Integrins play a role in cell signaling.

Types of Integrins:

• Table of Some Integrins:
  • Integrin α1β1 binds fibronectin and is ubiquitous.
  • Integrin α2β1 interacts with laminin and is found in muscles.
  • Integrin αLβ2 (LFA-1) interacts with Ig superfamily counterreceptors.
  • Integrin αIIbβ3 interacts with fibrinogen in platelets.

Major Families of Cell Adhesion Receptors:

• Families Include:
  • Integrins
  • Selectins
  • Cadherins
  • Ig Superfamily.

Cadherins:

• Function: Mediate homophilic adhesion, allowing cadherin molecules on one cell to bind to similar molecules on adjacent cells.
• Requirement of Ca2+: Cadherins require Ca2+ in the mixture to function as adhesion molecules.
• Stability of Connection: Multiple low-affinity interactions lead to strong attachments between cells, similar to a ‘velcro’ mechanism rather than permanent adhesion.

In-Class Activity:

• Topics for Discussion:
  • Multicellular organism development.
  • Classical cell sorting experiments.
  • Differences and similarities in integrins and cadherins.

Need to Knows:

1. Multicellular organisms develop from a single cell.
2. Classical cell sorting experiments led to the discovery of cell adhesion in multicellular organisms.
3. Integrins connect to the ECM.
4. Integrins mediate heterophilic interactions with ECM ligands (fibronectin, collagen, laminin) or with other cell surface receptors (VCAM-1, ICAM-1).
5. The ECM consists of cells and proteins, many of which form fibers.
6. Cadherins connect cells to each other.
7. Cadherins follow the homophilic binding paradigm to cadherins of the same type.
8. Cadherins are Ca2+-dependent.
9. Cadherins link via Catenins to the cytoskeleton.
10. Cadherins guide development via cell sorting.

Study Questions:

1. What is a multicellular organism?
2. What are the general differences between Integrin and Cadherin?
3. Name the superfamilies of CAMs.
4. How do you define cell adhesion?
5. Explain what the ECM is, describe its content and its importance for multicellular organisms.
6. Describe the homophilic and heterophilic binding patterns of CAMs.
7. What is the role of Ca2+ in Cadherin function?

Knowledge Terms:

• Extracellular Matrix (ECM): The network of proteins and polysaccharides between cells.
• Multicellular Organism: An organism composed of multiple cells.
• Homophilic CAMs: CAMs that bind to the same type of CAM on neighboring cells.
• Heterophilic CAMs: CAMs that bind to different types of CAMs.
• Cell Adhesion: The process by which cells interact and attach to neighboring cells or the ECM.
• Cadherin: A type of CAM that mediates cell-cell adhesion.
• Adhesion Molecule: A molecule that facilitates adhesion between cells.
• Integrins: A type of CAM that connects cells to the ECM.