Dr shaziatufail Assistant Professor Anatomy King Edward Medical University, Lahore, Pakistan INTEGRATION OF CELLS INTO TISSUES
Learning objective • How cells attach to neighboring cells • Extarcellular Matrix and Molecules that make up ECM • Role of ECM in cell signaling and intercellular communication
Cells in tissues can adhere directly to one another (cell-cell adhesion) through specialized integral membrane protein called cell adhesion molecules (CAMs) • Cells in animal tissues also adhere indirectly (cell-matrix adhesion) through the binding of adhesion receptors in the plasma membrane to components of the surrounding extracellular matrix (ECM); A complex interdigitating meshwork of proteins and polysaccharides screted by cells into the spaces between them • CAMs and ECM can bind cell together, and transfer of information between the exterior and interior cells. • Cell Junctions are relatively stable, ultrastructurally (ie in EM) distinct sites where cells are joined to each other or the extracellular matrix. • Adhesion molecules are one component of adhering junctions • Adhesion Molecules are cell surface molecules that stick to each other to allow cell-cell or cell-ECM adhesion
Cell-cell adhesions can be tight and long lasting or relatively weak and transient.
"the substance between cells" and the "material in the intercellular space“ • Structure and support to cells • Specific functions depending on types of cells it is associated • It is involved in signal transduction and intercellular communication • The constituent materials in this structure can vary widely; a. in plants…….cellulose, b. arthropods and fungi….. chitin b. in animals…proteins, and carbohydrates (mineral in bones). • Secreted by the surrounding cells. Molecules of Extracellular Matrix
Molecular Components of Extracellular Matrix • Proteoglycans • Are proteins that are heavily glycosylated • The basic proteoglycan unit consists of a "core protein" with one or more covalently attached to glycosaminoglycans chain(s) • point of attachment is a Serine residue to which the GAG is joined • Ser-Gly-X-Gly- (where X can be any amino acid residue, but Proline) • Proteoglycans may also help to trap and store growth factors within the ECM • Protein component of proteoglycans is synthesized by ribosomes while Glycosylation of the occurs in the Golgi apparatus • Heparin Sulfate………..development, angiogenesis, blood coagulation • Chondroitin sulfate .......cartilage, tendons, ligaments and walls of aorta • Karatan sulfate………. cornea, cartilage, bones and horns of animals
2. Fibers • Collagen • most abundant protein in the ECM , • produced as procollagen which is then cleaved by proteases to allow extracellular assembly • give structural support • Disorders such epidermolysisbullosa are due to genetic defects in collagen-encoding genes • Fibrillar (Type I, II, III, V, XI) • Facit (Type IX, XII, XIV) • Short chain (Type VIII, X) • Basement membrane (Type IV) • Other (Type VI, VII, XIII)
Elastin • give elasticity to tissues, allowing them to stretch when needed and then return to their original state • Present in blood vessels, lungs, skin • Synthesized by fibroblasts and smooth muscle cells • Are highly insoluble • Disorders such as cutis laxa and Williams syndrome are associated with deficient or absent elastin fibers in the ECM
3. Multi-adhesive matrix proteins • Fibronectin • Are glycoproteins that connect cells with collagen fibers in the ECM, allowing cells to move through the ECM. • Help at the site of tissue injury by binding to platelets during blood clotting and facilitating cell movement to the affected area during wound healing. • Laminin …. are proteins found in the basal laminae of virtually all animals
The Extracellular Matrix Participates in Signaling and Intercellular Communication • ECM participate in cell signalling • Extracellular matrix proteins interact CAMs and influence cell survival, gene transcription, cytoskeletal organization, cell motility, and cell proliferation. • Thus, outside-in and inside out signaling involves numerous interconnected pathways.
Extracellular Matrix Components Mediate Cell Signalling Via Integrins • Integrins are transmembrane receptors that mediate the attachment between a cell and ECM. • In signal transduction, integrins pass information about the chemical composition and mechanical status of the ECM into the cell.
Cell Junctions Types 1. Anchoring Junctions • Desmosomes • Hemidesmosomes • Adherens Junctions 2. Communicating (Gap) Junctions 3. Tight Junctions
Anchoring protein is plectin Integrin binds with laminin
Animal cells communicate by gap junctions Gap Junctions Connect Animal Cells • an animal cell may contain hundreds of gap junctions connecting to the neighboring cells. • Gap Junctions are too samll for proteins, but small molecules such as ATP, metabolic intermediates. Amino acids and co-enzymes can pass through them
Plant cells Communicate by Plasmodesmata • Instead of gap junctions, plants have plasmodesmata, which are membrane-lined bridges spanning the thick cell walls that separate plant cells from one another. • A typical plant cell have several thousand plasmodesmata