Cytoskeleton and Extracellular Matrix Notes

Cytoskeleton

Cell Migration and Actin Dynamics

  • Rearrangement of the basic meshwork creates filopodia and lamellipodia at the leading edge of a migrating cell.
  • Dynamic regulation of actin allows certain types of cells to migrate.
  • Filopodia: Thin protrusions of bundled actin filaments.
  • Lamellipodia: Thin, broad, sheet-like extensions containing extensive networks of branched actin.
  • Actin polymerization pushes the cell membrane forward.
  • The leading edge can create attachment sites called focal adhesions.
  • Contractile bundles and motor proteins contract and move the trailing edge forward.
Regulation by GTPases
  • Rho, Rac, and Cdc42 are GTPases that act as cell signaling integration points in regulating the actin cytoskeleton.
  • These GTPases influence the formation of:
    • Cortical actin meshwork
    • Contractile bundles
    • Lamellipodia
    • Filopodia

Extracellular Matrix (ECM) and Cell Organization

  • In multicellular organisms, cells are organized into tissues.
  • Tissues contain multiple cell types.
  • Different cell types are linked by connective tissue.
  • In animal cells, the connective tissue is mostly extracellular matrix (ECM).
  • In plant cells, the cell wall is the primary ECM.
Plant Cell Wall
  • The primary plant ECM is the cell wall, which:
    • Is made of polysaccharides.
    • Contains cellulose, which is made and secreted by the cell and assembled in the extracellular space.
    • Includes cellulose microfibrils, cross-linking polysaccharides, and pectin.
    • The middle lamina cements one cell wall to its neighbor.
Cellulose Organization
  • Microtubules direct the organization of cellulose.
  • Cellulose synthase complex makes many cellulose molecules and assembles them into a microfibril.
Animal Connective Tissues
  • Animal connective tissues are highly variable, including:
    • Tendons and dermis of the skin (tough and flexible).
    • Bone (hard and dense).
    • Cartilage (resilient, shock-absorbing).
  • The bulk of these tissues is extracellular matrix proteins.
ECM Production
  • Fibroblasts make extracellular matrix in skin, tendons, and other connective tissues.
  • Osteoblasts make extracellular matrix in bone.
  • Almost all extracellular matrix proteins are made in the cell, secreted, and then form large aggregates outside the cell.
ECM Components
  • Gels of protein and polysaccharide fill space and resist compression.
  • Proteoglycans: Glycosaminoglycans (GAG) and a core protein are key components, with cartilage having high levels of proteoglycans.
Collagen
  • Collagen provides tensile strength to the ECM and also provides the surface over which cells can crawl.
  • The type of collagen determines the properties of the tissue-specific ECM (e.g., bone vs. cartilage vs. blood vessels).
Collagen example
  • James Morris – the elastic skin man:
    • Genetic condition resulting from loss of the enzyme that converts procollagen into collagen results in Ehlers-Danlos Syndrome
    • Abnormal collagen -> stretchy skin
Epithelial Cells and Basal Lamina
  • Epithelial cells arrange into a sheet and form a lining or covering for a tissue.
  • Epithelial cells are polarized, with:
    • The apical side exposed to the outside of the tissue.
    • The basal side attached to connective tissue.
  • Laminin forms a basal membrane to support a sheet of epithelial cells.
  • Laminin forms the basal lamina, a thin, tough sheet of ECM present only at one side of a sheet of epithelial cells.

Cell Attachment to the ECM

  • Transmembrane proteins attach to the cytoskeleton inside the cell and to the ECM outside the cell.
  • Integrins are the primary family of proteins that do this job.
  • Different types of attachments are made depending on the ECM surface.
Fibronectin
  • Fibronectin forms dimers that have collagen binding sites and cell attachment sites.
  • Cell attachment sites bind to integrins.
  • Fibronectin provides a link between cells and collagen fibers.
Integrins
  • Integrins are transmembrane proteins that:
    • Bind fibronectin outside the cell.
    • Attach to the actin cytoskeleton inside the cell.
    • This attachment is critical for crawling cells.
  • Integrins attach to the basal lamina outside the cell.
  • Inside the cell, integrins attach to intermediate filaments in hemidesmosomes, which link cells to the basal lamina.