Cell-Cell Interactions Part 2

Cell-Cell Interactions Part 2

• Today's Agenda: Overview of tissue organization and ECM, connecting the cell to ECM (Integrins), ECM composition (three major protein categories), and regulation of cell adhesion (driving extravasation).

• Cells Organize into Tissues: Cells secrete proteins to form the extracellular matrix (ECM). A tissue is composed of cells and ECM. Four major tissue types: epithelial, connective, muscle, and nervous.

• Tissue Organization:

  • ECM is scarce in epithelial tissue, mostly a thin basal lamina.
  • ECM is abundant in connective tissue, where cells are sparse and do not directly contact each other. Cells in connective tissue are often supported by collagen fibers.

• Connective Tissue ECM Composition:

  • Composition is similar to basal lamina but with additional components.
  • Three major categories of ECM proteins exist:
    • Collagens: Provide structural integrity and mechanical strength. Sheet-forming collagens (like type IV) are in basal lamina; fibrillar collagens are in connective tissue.
    • Proteoglycans: Proteins with attached sugars that cushion the ECM and give it a gel-like consistency.
    • Multi-adhesive matrix proteins: Proteins that cross-link ECM proteins and bind integrins, connecting the ECM to the cell. Examples include laminin and fibronectin.

• Integrins: Transmembrane proteins on the cell surface that link the cell to the ECM and other cells. Integrins switch between active and inactive states based on signals.

  • Integrins are components of focal adhesions and hemidesmosomes.
  • Integrins can bind to other proteins on the cell surface as well as other proteins within the ECM.

• Basal Lamina: A sheet-like ECM found between epithelial and connective tissue.

  • The basal lamina is composed of collagen, proteoglycans, and multi-adhesive matrix proteins.
  • Integrins in cells interact with the basal lamina, attaching the cells to the tissue.

• Structure Differences in Basal Lamina:

  • Structure varies slightly based on tissue type,
  • In muscle: basal lamina surrounds muscle cells.
  • In epithelial tissue: basal lamina forms a sheet-like surface that the epithelial cells rest upon.

• ECM Components: Collagen in Basal Lamina:

  • Collagen IV proteins form a network by associating through their N- and C-terminal globular domains.
  • Three collagen IV molecules form a triple helix (subunit).

• ECM Components: Collagen in Connective Tissue:

  • Fibrillar collagens form fibers within connective tissue.
  • Collagen subunits associate along their lengths to form fibrils.
  • These fibrils assemble into fibers in connective tissue.
  • Collagen fibers are extremely strong and support the tissue structurally.
  • Collagen secretion occurs outside the cell, and procollagen is processed into collagen in the extracellular matrix.
  • Defects in collagen processing can result in hyperflexible skin.

• ECM Components: Proteoglycans:

  • Proteoglycans have GAGs (glycosaminoglycans) attached that can form large aggregates.
  • GAGs commonly have a gel-like consistency that resists compression within tissues.
  • GAGs are assembled onto proteoglycans in the Golgi.

• ECM Components: Multi-adhesive Matrix Proteins:

  • Multi-adhesive matrix proteins help form the ECM by crosslinking proteins.
  • Multi-adhesive matrix proteins bind to other proteins and to integrins, which binds them to the cell.
  • Examples: laminin and fibronectin.
    • Fibronectin has domains for binding to different ECM components and to integrins, anchoring collagen in tissues to cells.
    • Laminin is found within the basal lamina and has binding domains for other ECM proteins and integrins.

• Regulation of Cell Adhesion in Extravasation:

  • Extravasation is how leukocytes (white blood cells) migrate to infection sites.
  • Leukocytes initially transiently adhere to blood vessel walls using loose adhesion (selectins binding to glycoproteins along the vessel).
  • Cells begin to roll along the blood vessels.
  • Upon reaching a signal on site at infection, cells switch to tight adhesion (integrins bind to proteins like ICAM-1) allowing cells to leave the blood vessel and enter the infected tissue.

• Reminders: Exam 4 review, final assignment, and attendance policies for the upcoming Friday and Monday classes and mandatory attendance.

• Meme/TikTok Assignment: Submit a meme/TikTok conveying a cell biology concept this week for extra credit.

Explore the intricate organization of tissues and their extracellular matrix (ECM) in this quiz. Understand the role of integrins in connecting cells to the ECM, the composition of different ECM proteins, and how cell adhesion is regulated. This is fundamental to understanding tissue structure and function.