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Cellular Interactions with the Environment: ECM Overview

Explore how cells interact with extracellular materials to form tissues crucial for cellular activities. Learn about the extracellular matrix, basement membrane, and various types of collagen affecting tissue structure and function. Discover the roles of proteoglycans in maintaining tissue integrity and hydration.

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Cellular Interactions with the Environment: ECM Overview

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  1. Interactions Between Cells and Their Environment

  2. Introduction • Cells don’t exist alone. • Cells interact with extracellular material to form defined tissues. • These interactions are crucial to the formation of epithelial tissue and connective tissue, which are crucial for various cellular activities.

  3. Introduction (Cont.) • Cell migration, cell growth, cell differentiation, 3-D organization of tissues and organs that emerges during embryonic development.

  4. Overview of cell organization into tissues • Click to edit Master text styles • Second level • Third level • Fourth level • Fifth level

  5. 7.1 The Extracellular Space (1) • The glycocalyx (cell coat) is formed from carbohydrate projections form the plasma membrane. • Outer surface of the plasma membrane

  6. 7.1 The Extracellular Space (cont.) • Gycocalyx • Mediate cell-cell and cell-substratum interactions • Provide mechanical protection to cells • Barrier to particles moving toward plasma membrane • Bind important regulatory factors

  7. The Extracellular Space (cont.) • The extracellular matrix (ECM) is an organized network of proteins and polysaccharides beyond the plasma membrane. • “Glue” that holds cells together • It often plays a regulatory role in determining shape and activities of the cell.

  8. Organization of the ECM

  9. The Extracellular Space (cont.) • ECM (continued) • The basement membrane (basal lamina) is a continuous sheet that underlies epithelial tissue and surrounds blood vessels. • Helps maintain cells attached. • Serves as substratum for cell migration. • Forms a barrier to macromolecules.

  10. The basement membrane

  11. Extracellular matrix • Gel-like “ground substance” • Primarily made of polysaccharides • Gylycosaminoglycans (GAGs) • proteoglycans • Fibrous proteins • Collagen, laminin, elastin, fibronectin • Structure and adhesive functions

  12. The Extracellular Space (cont.) • Collagens – fibrous glycoproteins found only in the ECM. • Collagen is the most abundant protein in the human body. • Provide high tensile strength. • Each collagen is restricted to particular locations in the body. • All collagens are a trimer of polypeptide chains (α chains) and 3 polypeptide chains are wound around each other.

  13. The structure of collagen I

  14. Major types of collagen • Type I collagen • The chief component of tendons, ligaments, and bones. • Type II collagen • Represents more than 50% of the protein in cartilage and is the major component of the vitreous body of the eye. • It is also used to build the notochord of vertebrate embryos.

  15. Type III collagen • Strengthens the walls of hollow structures like arteries, the intestine, and the uterus. • Type IV collagen • Forms the basal lamina of epithelia. (The basal lamina is often called the basement membrane.)A meshwork of Type IV collagens provides the filter for the blood capillaries and the glomeruli of the kidneys.

  16. The Extracellular Space (cont.) • Collagens (continued) • Provide the insoluble framework that determines mechanical properties of the matrix. • Abnormalities in collagen formation lead to serious disorders.

  17. The Extracellular Space (cont.) • Collagens type I, II, III are fibrillar collagens • Assemble into rigid, cable-like fibrils (assembles like fibers) • Example: tendon – collagens are parallel to tendons thus parallel to pulling actions

  18. The Extracellular Space (cont.) • Abnormalities in fibrillar collagens formation can lead to serious disorders • Mutation in in genes encoding type I collagen can produce osteogenesis imperfecta • Extremely fragile bones, thin skin, and weak tendons

  19. The Extracellular Space (cont.) • Mutation in genes encoding type II alter the properties of cartilage tissue causing dwarfism and skeletal deformities • Mutations in other collagens genes that are related in collagen matrix structure can lead to Ehler-Danlos sydromes • Hyperflexible joints and extensible skin

  20. The Extracellular Space (cont.) • Not all collagens form fibrils. • Collagen type IV is non-fibrillar, and is restricted to the basement membrane.

  21. The Extracellular Space (cont.) • Mutations in type IV collagen genes causes Alport syndrome • A kidney disease in which glomerular basement membrane is disrupted

  22. The Extracellular Space (cont.) • Proteoglycans – protein-polysaccharide complex, with a core protein attached to glycosaminoglycans (GAGs). • GAGs • Have a repeating disaccharide structure. • Negatively charged

  23. The Extracellular Space (cont.) • Negatively charged GAGs attract lots of cations, which in turn attract water forming a porous, hydrated gel. • Function: • to be able to withstand compressional forces through hydration and swelling pressure (turgor) to the tissue

  24. Click to edit Master text styles • Second level • Third level • Fourth level • Fifth level

  25. Structure of a proteoglycan complex

  26. Structure of a proteoglycan complex

  27. The Extracellular Space (cont.) • Forms complement to collagen molecule • Together, they give cartilage and other extracellular matrices strength and resistance to deformation • Example: ECM of bones • Collagen + Proteoglycans + calcium sulfate ions = bones • GAG chains of proteoglycans also act as binding sites for many growth factors

  28. The Extracellular Space (cont.) • Fibronectin (Fn) • Helps cells attach to matrix • Fn has binding sites for other components of the ECM. • RGD • Binding of Fn to the cell occurs via the RGD sequence – binds to integrins

  29. Structure of fibronectin

  30. The Extracellular Space (cont.) • Fibronectin (FN) is involved in many cellular processes, including tissue repair, embryogenesis, blood clotting, and cell migration/adhesion. • Fibronectin sometimes serves as a general cell adhesion molecule • FN also can serve to organize cellular

  31. The Extracellular Space (cont.) • Laminins – extracellular glycoproteins consisting of three polypeptide chains linked by disulfide bonds. • Help cell migration during development. • Components of basement membranes.

  32. The Extracellular Space (cont.) • Dynamic Properties • The ECM can be stretched during tension. • ECM materials degraded by matrix metalloproteinases (MMPs). • MMPs possibly involved in tissue remodeling, embryonic cell migration, wound healing , and formation of blood vessels. • Excessive MMPs causes arthritis, hepatitis, atherosclerosis, tooth and gum disease and tumor progression

  33. 7.2 Interactions of Cells with Extracellular Materials • Integrins – family of membrane proteins composed of heterodimers with α and ß subunits. • Have a major role in integrating extracellular and intracellular environments. • Another role is adhesion of cells to their substratum or other cells.

  34. Model of integrin activation

  35. Interactions of Cells with Extracellular Materials (cont.) • Integrins (continued) • Linkage between integrins and their ligands mediates adhesion between cells and their environment. • Binding of proteins to integrins is facilitated by tripeptide RGD.

  36. Interactions of Cells with Extracellular Materials (cont.) • Integrins (continued) • Cytoplasmic domains of integrins contain • binding sites for a variety of cytoplasmic • proteins. • Integrins make the connection between • the ECM and the cytoskeleton.

  37. Blood clotting • Injury conformational change in platelets’ integrin activation inc. fibrinogen affinity aggregation of platelets Synthetic RGD peptides -> inhibit blood clot formation

  38. Interactions of Cells with Extracellular Materials (cont.) • Focal adhesions are found at the cell membrane where the cytoskeleton interacts with proteins of the extracellular matrix • Focal adhesions – scattered, discrete sites • for cell adhesion to their substratum in vitro. • They may act as a type of sensory structure. • Are also implicated in cell locomotion.

  39. The clustering of integrins at these sites attracts a large complex of proteins and initiates intracellular regulatory processes, by which such events as cell migration and anchorage-dependent differentiation are controlled. • Focal adhesion kinase (FAK) is a protein tyrosine kinase which is recruited at an early stage to focal adhesions and which mediates many of the downstream responses.

  40. Focal adhesions

  41. Focal adhesions

  42. Interactions of Cells with Extracellular Materials (cont.) • Hemidesmosomes are cell-substratum adhesion sites that connect the extracellular matrix to the keratin cytoskeletonbasal attachments of epithelial cells to the basement membrane in vivo.Contain a dense plaque with filaments consisting of keratin.Keratin filaments are linked to the ECM by membrane-spanning integrins.

  43.  form rivet-like links between cytoskeleton and extracellular matrix components such as the basal lamina that underlie epithelia

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