lect 6: extracellular matrix Flashcards
text: what are multicellular organisms built from?
multicellular organisms are built from organized collections of cells
text: what are tissues?
-most of the cells in multicellular organisms are organized into cooperative assemblies called tissues
-tissues are organized into organs
text: what are tissues composed of?
-tissues composed not only of cells, with their internal framework of cytoskeletal filaments, but also of extracellular matrix
text: what is the extracellular matrix? Cell junctions?
the material that cells secrete around themselves; it is this matrix that gives supportive tissues such as bone or wood their strength
-at the same time, cells can also attach to one another directly
-cell junctions link cells together in the flexible epithelial tissues of animals. These junctions transmit forces either from the cytoskeleton of one cell to that of the next, or from the cytoskeleton of a cell to the extracellular matrix
text: organization of cells?
-all the tissue components have to be appropriately organized and functionally coordinated, and many of them require continual maintenance and renewal
-cells die and have to be replaced with new cells of the right type, in the right places, and in the right numbers
-disorders of tissue renewal are a major medical concern, and those due to the misbehavior of mutant cells underlie the development of cancer
text: have animals and plants always evolved together?
they have evolved their multicellular organization independently, and their tissues are constructed on different principles
-animals eat other living things, and they are often eaten by other animals. For these reasons, animals must be capable of rapid movement; their tissues, therefore, must be flexible and the cells that compromise those tissues must be able to generate and transmit forces and to change shape quickly
-plants, by contrast, are sedentary: their tissues are more or less rigid, yet their cells are weak and fragile if separated from the stiff supporting matrix that surrounds them
text: what is the supportive matrix in plants?
the cell wall, a boxlike structure that encloses, protects, immobilizes and shapes each cell
-plant cells themselves synthesize, secrete and control the composition of this extracellular matrix: a cell wall can be thick and hard, as in wood, or thin and flexible, as in a leaf
-the principle of construction is the same in either case: many tiny boxes are cemented together, with a delicate cell living inside each one
text: what do animal cells consist of?
animal tissues are more diverse
-they consist of both cells and extracellular matrix, but these components are organized in many different ways
-in specialized connective tissues, such as bone or tendon, extracellular matrix is plentiful and mechanically all-important; in other tissues, such as muscle or the epidermis of the skin, extracellular matrix is scanty, and the cytoskeletons of the cells themselves carry the mechanical load
what are the learning objectives of this lecture?
-identify the structures and functions of the extracellular matrix in animal tissue
-describe the localization of the ECM relative to cells in an animal tissue
-know the structure/function of the basic components of the ECM
what is an overview of the extracellular matrix (ECM)?
-environment surrounding cells
varies between tissues
-nervous (brain, spinal cord)
-connective (joints)
-epithelial (skin, airways)
-muscle (heart)
what is the glycocalyx?
remember plasma membrane glycoproteins and glycolipids
-CHO projections form part of the glycocalyx
more prominent in certain cell types
functions
-mediator of cell-cell and cell-substratum (layer underneath it) interactions
-mechanical protection
-barrier to molecular movement towards the plasma membrane
-regulatory factor binding site
what does the glycocalyx look like?
what is the basement membrane?
also known as the basal lamina
-thin, dense layer of ECM
locations
-surrounds nerves, muscles, fat cells
-underlies epithelial tissues: epidermis of skin, lining GI/resp tracts, blood vessel endothelium
what is the extracellular matrix?
-varies between tissues/organisms
-ECM proteins are fibrous, c/t intracellular are globular
-proteins secreted by cell into extracellular space
-assemble into interconnected 3D network
what are the 3 major molecules in the ECM?
what are adhesive proteins?
-hold cells together which forms into organized tissue
-main proteins are integrins and cadherins
what are the structural proteins?
-tensile and compressive strength (pulled apart and compressed)
-types: collagen, elastin, keratin
what is collagen?
-large family of fibrous glycoproteins ONLY in ECM
-produced primarily by fibroblasts
most abundant protein in human body 25%
-28 fiber types, mixed in ECM
-most common types I-IV
-I=bone, skin, tendon (90%)
-II=cartilage
-III=reticulin, blood vessels
-IV=basement membrane
what is the structure of type I collagen?
-collagen molecules: triple helix of alpha chains
-large amount of proline residues
-staggered alignment of rows
post translational modification
-hydroxylation of proline and lysine: this increases stability of fiber
what is the collagen network of basement membrane?
-type IV collagen
-non-helical segments + terminal globular domains (c/t type I)
-creates lattice-like structure
how does collagen act as a framework?
-insoluble framework->determines mechanical properties of matrix
correlate tissue properties with 3D organization of collagen
-tendons
-cornea
what is the collagen framework in the cornea?
-ordered packing
-tissue transparency (unique)
what is vitamin C deficiency (scurvy)?
problems with ECM structure
-vitamin C (ascorbic acid)
-manifestations include: bleeding gums, loose teeth, easy bruising
-why?: cofactor (vit C) for hydroxylation of collagen lysine, proline residues (contribute to structure and stability so when doesn’t happen, it leads to the breakdown of collagen)
what is another disease caused by problems with ECM structure?
-occupation: truck driver for 28 years
-skin damage on left side of his face
-disease is dermatoheliosis from UV radiation exposure
-treatment is skin care with collagen replacement
pathophysiology includes
-decreased collagen synthesis
-increased collagen degradation
-disorganized elastin
what are proteoglycans?
-protein core + sugar chains (the sugar being glycosoaminoglycan which is an amino sugar)
-function: space-filler, hydration and cushioning
-examples include fibronectin and laminin
what is the structure of proteoglycans?
-sugar» protein (way more sugars than proteins)
-repeating disaccharide structure: A-B-A-B (where A and B are different)
-act as acids at physiological pH
-++ acidic d/t carboxyl and sulfate groups attached to sugars: NEG changes attract ions/H2O which gives a gel consistency
-found in large amounts in basement membranes and cartilage
what is fibronectin?
-2 polypeptide chains held together by disulfide bonds
-molecular construction: there are 30 Fn domains
-Fn domains also found in blood clotting membranes and membrane receptors
numerous binding sites:
ECM components, which lead to a stable, interconnected network
-collagen
-proteoglycans, fibronectin
cell surface receptors
-attach cell and ECM
what is the role of fibronectin in development?
-development-cell migration
-migrating cells guided by proteins ECM
-ex: neural crest cells
-ex: organ formation: branching/cleft formation
what is laminin?
-family of at least 15 extracellular glycoproteins
-3 polypeptide chains linked by disulfide bonds
-strengthen basement membrane
like fibronectin
-influence a cell’s potential for migration, growth, differentiation
-role in development of neuronal outgrowth
what is the model of basement membrane scaffold?
what are the dynamic properties of ECM?
spatially
-ECM fibrils can stretch several times their normal length
temporally
-ECM components are under continual degradation and reconstruction to allow ECM remodeling (development and injury)
what are MMPs?
matrix metalloproteinases (MMPs) degrade ECM components. thought to be involved in:
-tissue remodeling
-embryonic cell migration
-wound healing
-formation of blood vessels (angiogenesis)
abnormal expression of MMPs is linked to a variety of diseases
what is the simplistic summary of the ECM?
-collagen fibrils form the basic insoluble framework of the ECM
-laminins form a parallel network
-proteoglycans are the fillers of the ECM (cushioning, interacting with water)
-fibronectins and laminins strengthen the ECM (due to their many binding sites)
