INTEGRATION OF CELLS INTO TISSUES Dr shazia tufail Assistant Professor Anatomy King Edward Medical University, Lahore, Pakistan

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

Levels of Organization in Living Things

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.

Molecules of Extracellular Matrix "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.

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 epidermolysis bullosa 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

ECM participate in cell signalling 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