Extracellular Matrix and Wound Healing

• consists of a heterodimer between an alpha and beta integrin • glycoprotein • anchor the ECM to the cell membrane and the cytoskeleton • are receptors that have ligands on either side of the cell membrane, and those ligands may be adaptor proteins • many mutations in integrin genes are lethal

uses integrins to anchor actin filaments in cell to extracellular matrix

uses integrins to anchor intermediate filaments in a cell to extracellular matrix

connected by cell-cell junctions and have a limited ECM • ECM is the basal lamina/basement membrane • usually “outer” layer like skin

secrete extracellular matrix

• heterotrimer: alpha, beta, and gamma subunits • glycoprotein • stay near the cell membrane and help cells stick together • helps organize basal membrane • helps with adhesion and migration of cells

• makes up majority of ECM • triple helix = fibril • glycoprotein • can form sheets • can cross the cell membrane • can be protein part of proteoglycans • can be associated with fibrils (hanging off other fibers) • I and III that form fibers are most prevalent in cell

• associated with collagen I and V • hypermobility • elastic but fragile skin: easily torn and may scar easily

• associated with collagen IV (basal lamina) • progressive kidney failure: decreased filtering function of glomeruli • hearing loss: can hear but message isn’t transmitted to brain • eye deformities: lens shape or retina color can change but no loss of function

• sugar-modified peptides (more sugar than protein) - very big

• type of proteoglycan - interacts with and regulates collagen fibers

• type of proteoglycan • interact with elastins and influences cell migration • important in wound healing

• type of proteoglycan - found in cartilage

• only transmembrane proteoglycan - intracellular domain interacts with actin (actin-linked cell matrix junction)

• sugar that is on the proteoglycans • only a sugar, but can interact with other proteins • very hydrophilic, like to interact with water • take up a lot of space

• flexible but remember their original shape • composed primarily of hydrophobic amino acids • cross-linked at lysine residues • not glycosylated (strange for secreted protein) • major ECM component of arteries

• hold other ECM components together and binds cell surface receptors • multiple binding domains • one gene for fibronectin but alternative splicing allows variation • glycoprotein • scaffolding function is important in wound healing

• function to remodel ECM • require Ca++ or Zn++ to work • each ECM component has its own special MMP to degrade it • MMPs are turned off (by Tissue inhibitors of MMPs- TIMPs) during wound healing by competitive inhibition

fetal and oral wounds

fetal/ora: normal normal scar: decreased hypertrophic: decreased keloid: increased

fetal/oral: regenerative normal: myofibroblasts hypertrophic: increased myofibroblasts keloid: more increased

fetal/oral: decreased normal: normal hypertrophic: increased keloid: more increased

fetal/oral: parallel; basketweave normal: parallel and crosslinked hypertrophic: parallel-ish and thinner fibrils keloid: disordered and thicker fibrils