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Cell Adhesion and Communication Shu-Ping Lin, Ph.D. Institute of Biomedical Engineering E-mail: [email protected] Website: http://web.nchu.edu.tw/pweb/users/splin/ Date: 12.13.2010 Extracellular Matrix (ECM) – Animal Cells What leads to the variety of the ECM? Different kinds of molecules; both proteins and proteoglycans; ratio of different components Besides providing stability to the physical structure of tissues, why else is the ECM important to cell function? Influences migration and development of cells, cell proliferation, cell shape The ECM is usually associated with connective tissue. What are some examples of connective tissue? Bone, ligaments, tendons, cartilage Cell-cell and cell-substrate adhesion molecules (CAMs and SAMs, respectively) are candidates for morphoregulators. Soluble Ligand-ReceptorMediated Communication Cell-cell signaling carried out by soluble ligands is a prominent mode of cell-cell communication in animals. Common elements of all these signaling modes are signal-receiving proteins or receptors, transducers and effectors Ligand signaling: Endocrine signaling Paracrine signaling Autocrine signaling http://www.ncbi.nlm.nih.gov/books/NBK28317/ Endocrine signaling: hormones act on target cells distant from their site of synthesis. In animals, blood transports hormones from their sites of release to their targets. Paracrine signaling: signaling molecules only affect cells in close proximity Conduction of electrical impulse from one nerve cell to another and to muscle cell by neurotransmitters and neurohormones Autocrine signaling: cells respond to substrates (growth factors) that they themselves release, utilizing signal amplification component of pathway to alter growth and differentiation. Tumor cells overproduce and release growth factors that stimulate uncontrolled growth. http://www.ncbi.nlm.nih.gov/books/NBK28317/ Extracellular Matrix (ECM) Cells in multicellular organism are in contact with other cells or with extracellular matrix (ECM). 2 fundamental types of ECM: 3-dimensional matrix: completely surrounds cells and found commonly in tissues such as bone, cartilage, and tendon, as well as surrounding epithelial components of glandular organs such as breast or prostate glands 2-dimensional basal lamina: interacts with basal surface of all epithelia Epithelial cells form sheets that contact one another at their lateral borders and contact the 2-dimensional extracellular matrix at basal surface. 2-dimensional basal lamina is in turn in contact with a 3dimensional ECM in which other cells are suspended. 2D and 3D ECMs of animal cells are made up of 4 major components: Structural components, one or more members of collagen family, such as fibrous collagens (type I, 3D ECM) and nonfibrous collagens (type IV, 2D ECM) Adhesive component responsible for interacting with cells and with other ECM, glycoproteins – attach cells to matrix – fibronectins (3D ECM) & laminins (2D ECM) Space fillers, such as sulfated and hydrated glycosominoglycans and proteoglycans, heparin and heparan sulfate vary in their carbohydrate, sulfate, and linker protein content from tissue to tissue. Elastic components such as elastin. These ECMs highly found in lungs is continually exposed to stretching forces. Modes of cell-ECM interactions. Endothelial cells are deposited on 2D basal lamina surface, migrating fibroblasts interact with 3D matrix. Cell-ECM interactions lead to imposition of physical force onto cells. Figure illustrates interaction of circulating white blood cell with endothelial cells by cell-cell adhesion, arrows are direction of blood flow and forces. Epithelial Cell Adhesion to Basal Lamina – Cell Fate Cells in contact with ECM and with neighboring epithelial cells are limited in their ability to proliferate. Cells lose contact with other cells while adhering to ECM can proliferate (a), whereas loss of attachment to ECM results in apoptosis (b). Many tumor cells do not undergo apoptosis when detached from ECM and have subverted role of cell adhesion in regulation of cell proliferation. Plants Cell Junctions Molecular Staples Plasmodesmata Animals Animal cells have no cell walls Some are surrounded by a matrix of cell secretions and other material Tight junctions Adherens junctions Gap junctions plasmodesma Animal Cell Junctions free surface of epithelial tissue (not attached to any other tissue) examples of proteins that make up tight junctions gap junctions adhering junction basement membrane