Chapter 20 notes – connective tissues etc
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Chapter 20 notes – connective tissues etc Chapter 20 notes – connective tissues etc Document Transcript

    • Chapter 20 Notes – Connective Tissues etc
    • Most cells in mulitcellular organisms are organized into cooperative assemblies called tissues, such as the nervous, muscle, epithelial, and connective tissues.
    • Cells are made from the EXM , which cells secrete around themselves. – it is the matrix that gives supportive tissues such as bone or wood their strength.
    • Extracellular Matrix and Connective Tissues
    • Strength of a plant tissue comes from the cell walls, formed like boxes that enclose and protect the cells.
    • Plant Cells Have Tough External Walls
    • A primary cell wall usually forms first, which can slowly expand to accommodate cell growth
    • The driving force for growth is the pressure , turgor pressure, as a result of the osmotic imbalance between the outside and inside of the cell.
    • A secondary cell wall forms once cell growth stops
    • Cellulose Microfibrils Give the Plant Cell Wall Its Tensile Strength
    • Cell walls derive their tensile strength from cellulose.
    • Synthesized on the outside of the cell by enzyme complexes in the PM
    • Complexes transport sugar monomers across the PM and incorporate them into a set of growing polymer chains at their points of membrane attachment.
    • Each set of chain forms a cellulose microfibril.
    • Under the PM, microtubules are aligned exactly with the cellulose microfibrils just outside the cell, so the MT are thought to act as tracks to guide the movement of the enzyme complexes
    • Cellulose microfibrils are interwoven with other polysaccharides and some structural proteins, all bonded together to form a complex structure that resists compression and tension.
    • Lignin – usually in woody tissue, is deposited within the matrix to make it more rigid and waterproof.
    • Cellulose will not stretch, so the ori
    • entation of the cellulose in the cell will determine in which direction it will grow.
    • Animal Connective Tissues Consist Largely of Extracellular Matrix
    • There are four major types of tissues in animals
    • Connective
    • ECM is plentiful and carries mechanical load
    • Can be tough like tendons or dermis of skin or dense like bone, or resilient like cartilage, or soft like the jelly of the eyes.
    • Bullk of this is a fibrous protein called collagen.
    • Epithelial
    • ECM is little and cells are directly adhered to one another and carry mechanical load themselves.
    • Nervous
    • Muscular
    • Collagen Provides Tensile Strength in Animal Connective Tissues
    • Collagens are the chief proteins in bon, tendon, and skin and they constitute for about 25% of the total proteins in mammals
    • 3 collagen polypeptide chains are wound around one another in a rope-like helix
    • assemble into ordered polymers called collagen fibrils
    • pack together into thicker collagen fibers
    • According to the type fo tissue, the connective-tissue cells that manufacture and inhabit the matrix go by various names. They make the collagen and other organic components of the matrix
    • Fibroblasts
    • Skin, tendons, and other connective tissue
    • Osteoblasts
    • Bone
    • Synthesized internally and transported via exocytosis
    • Cells secrete procollagen first, which obstruct assembly to collagen fibrils so the cell doesn’t choke itself in its own product
    • Procollagen proteinases cut terminal of terminal domains to allow assembly only after the molecules are in the EXS
    • Mutations result in less tensile strength in skin and stretchability
    • Cells in tissue must degrade matrix as well as make for tissue growth, repair, and renewal.
    • Cells Organize the Collagen That They Secrete
    • Connective-tissue cells control the orientation of the collagen
    • Deposit collagen in oriented fashion
    • Rearrange it
    • Fibroblasts shape collagen they secrete
    • If in culture where collagen is disorganized, fibrolasts tug on the meshwork and compact it
    • Fibroblasts are important for healing wounds
    • Integrins Couple the Matrix Outside a Cell to the Cytoskeleton Inside It
    • Fibronectin provides a linkage for cells to crawl over one another.
    • One part of fibronectin binds to collagen, while another forms an attachment site for a cell.
    • The binding site of a cell is a receptor protein called integrin, which spans the cell’s PM and binds to fibronectin
    • Integrin’s intracellular domain binds to actin filaments inside the cell.
    • Bindong to a molecule on one side of the membrane causes the integrin molecule to stretch out into an extended, activated state so that it can then latch onto another molecule on the opposite side
    • An intracellular signal can activate the integrin causing it to reach out and grab hold of an extracellular structure
    • Binding to an extracellular structure can activate intracellular signaling cascades via protein kinases that associate with the intracellular end of the integrin.
    • Leucocyte adhesion deficiency
    • When integrins on WBCs cannot help a cell crawl out of blood vessels at sites of infection
    • Individuals lacking integrins in blood platelets cannot clot blood and bleed excessively
    • Gels of Polysaccharide and Protein Fill Spaces and Resist Compression
    • Proteoglycans
    • EXC proteins linked to a special class of negatively charged polysaccharides, glycosaminoglycans (GAGs)
    • Dense, compact, connective tissues such as tendons and bones, the proportion of GAGs is small and the matrix is almost all collagen
    • Jellylike substance in the eye consist of almost only one type of GAG, plus water, with only a small amount of collagen.
    • Strongly hydrophilic which provides hydrate space in around cells
    • Negative charges attract ions
    • Osmotically active, causing large amounts of water to be sucked into the matrix, causing swelling balanced by tension in collagen fibers interwoven with proteoglycans.
    • Cartilage matrix of knee joint is hugely tough
    • Help resist compression
    • Can make gels of densities that help filter molecules
    • Bind secreted GFs and other proteins that serve as signals for the cells.
    • Can guide cell movement through matrix
    • Epithelial Sheets and Cell Junctions
    • Epithelium – sheet of cells covering an external surface or lining an internal body cavity
    • Can be stratified or simple epithelium, only one cell layer like the gut
    • Epithelia cover the external surface of the body and line all its internal cavities.
    • Cells joined in sheet create a barrier that has the same significance of the PM of cells.
    • Epithelial Sheets Are Polarized and Rest on a Basal Lamina
    • Epithelial sheets have two faces:
    • Apical surface
    • Free and exposed to air or watery fluid
    • Basal surface
    • Rests on some other tissue, usually connective, to which it is attached
    • Supported by a thin, tough sheet of ECMatrix, called the basal lamina, composed of a specialized type of collagen (Type IV) and other macromolecules, one includes laminin, which provides adhesive sites for integrin molecules in the PM of epithelial cells, and thus serves a linking role like that of fibronectin in connective tissues.
    • Absorptive cells, which take up nutrients, and goblet cells, which secrete mucus, in the intestines
    • Tight Junctions Make an Epithelium Leak-Proof and Separate Its Apical and Basal Surfaces
    • Cell junctions – Specialized region of connection between two cells or between a cell and the ECM
    • Tight Junctions
    • Seal neighboring cells together so the water-soluble molecules cannot easily leak between them.
    • Formed from claudin and occluding proteins, which are arranged in strands along the lines of junctions to create seals.
    • Without, the pumping activities of apsorptive cells would be futile and the concentration on both sides of the epithelium would be the same
    • The TJs around the apical side of cells prevents diffusion of membrane proteisn within the PM and keep the apical domain of the PM different form the basal domain.
    • TJs are sites of assembly for the complexes of intracellular proteins that fovern apico-basal polarity in the interior of the cell.
    • Cytoskeleton-linked Junctions Bind Epithelial Cells Robustly to One Another and to the Basal Lamina
    • There are three types of junctions that hold an epithelium together by forming mechanical attachments:
    • Adherens junctions (and Desmosomes)
    • Bind one epithelial cell to another
    • Built around transmembrane proteins that belong to the cadherin family
    • A cadherin molecule in the PM of one cell sinds directly to an identical cadherin molecule in the PM of its neighbor.
    • Such binding of like to like is called homophilic binding.
    • In the case of cadherins, binding also requires that Ca2+ be present in the EXC medium – hence its name
    • Adherens Junction
    • Each cadherin molecule is tethered inside its cell, via several linker proteins, to actin filaments.
    • Form a continuous adhesion belt, located near the apical end of the cell just below the TJs, around each of the interacting epithelial cells. Actin is therefore connected form cell to cell across the epithelium.
    • By shrinking the apical surface along one axis, the sheet can roll itself up into a tube.
    • Or it can make a cup-shaped concavity and eventually create a vesicle that may pinch off from the rest of the epithelium
    • Desmosomes
    • These cadherins connect to intermediate filamets – specifically to keratins, which are the types of intermediate filaments found in epithelia
    • Hemidesmosomes
    • Bind epithelial cells to the basal lamina
    • Attachments of epithelial cells to the extracellular matrix beneath them
    • The molecule that forms the external adhesion spans the membrane and is linked inside the cell to strong cytoskeletal filaments
    • Gap Junctions Allow Ions and Small Molecules to Pass from Cell to Cell
    • Another type of epithelial cell junction
    • Gap junction – communicating cell-cell junction that allows ions and small molecules to pass from the cytoplasm of one cell to the cytoplasm of the next.
    • Connexons form the channels across two PMs and allow inorganic ions and small water-soluble molecules to move directly from cytosol to cytosol.
    • Creates an electrical and metabolic coupling between the cells.
    • GJs in heart muscle cells proved electrical coupling that allows electrical waves of excitation to spread through the tissue.
    • These waves trigger the coordinated contraction of the cells, producing a regular heart beat.
    • Can be opened or closed as needed in response of extracellular signals.
    • Dopamine, a neurotransmitter, reduces GJ communication within a class of neurons in the retina in response to an increase in light intensity.
    • This reduction in GJ permeability changes the pattern of electrical signaling and help the retina switch from using rod photoreceptors, which are good detectors of low light, to cone photoreceptors, which detect color and fine detail in bright light.
    • Plasmodesmata in plant cells are the functional couterpart of GJs
    • Cytoplasmic channels lined with PM, and the cytoplasm becomes continuous form one cell to the next.
    • Tissue Maintenance and Renewal
    • Tissues Are Organized Mixtures of Many Cell Types
    • All tissues need mechanical strength, which is often supported by a supporting bed or framework of connective tissue inhabited by fibroblasts
    • In the connective tissue blood cells lined with endothelial cells supply oxygen, nutrients and waste disposal
    • Three main factors contribute to the stability and organization of tissues:
    • Cell communication
    • Social signals from other cells
    • Live and die when required
    • Selective cell-cell adhesion
    • Cells have different cadherins and adhesion molecules , so the stick selectively by homophilic binding
    • Selectivity of adhesion prevents mixing of tissue types.
    • Cell memory
    • Patterns of gene expression
    • Only cells of a type divide to form another cell of the same type
    • Different Tissues Are Renewed at Different Rates
    • Nerve cells usually last a lifetime
    • Intestinal lining cells replaced every few days
    • Bone replaces roughly every ten years in humans
    • Old bone matrix is eaten by osteoclasts
    • Osteoblasts deposit new matrix
    • RBCs are generated in the marrow and last 120 days
    • Skin is replaced every two months
    • Stem Cells Generate a Continuous Supply of Terminally Differentiated Cells
    • Terminally differentiated cells lie at the end of their developmental pathway
    • Proliferating precursor cells are replacements for TD cells.
    • Derive from stem cells
    • Can divide without limit
    • Divides to another stem cell and then to a TD cell
    • RBCs derive from a hemopoietic stem cell found in the bone marrow
    • Specific Signals Maintain the Stem-Cell Populations
    • Signals are from the stem cells themselves, progeny, and surrounding tissues
    • Wnt proteins, a class of signaling molecules, serve to keep the stem cells and precursor cells at the base of each intestinal crypt in a proliferative state: the cells in these regions both secrete Wnt proteins and express the receptors for these proteins; and through positive feedback, stimulate themselves to continue dividing.
    • Stem Cells Can Be Used to Repair Damaged Tissues
    • Embryonic stem cells (ES cells)
    • Can proliferate indefinitely in culture and retain unrestricted developmental potential and are thus said to be pluripotent
    • Can maybe one day be used to grow full organs
    • Problem: if the cells are genetically different, they may be detected and destroyed by the immune system, but therapeutic cloning could prevent this.
    • Therapeutic Cloning Could Provide a Way to Generate Personalized ES Cells
    • Reproductive cloning – the cloning of entire multicellular animals
    • Therapeutic cloning – ES cells derived in culture, with the aim of generating various cell types that can be used for tissue repair, rather than a whole cloned animal
    • Genes artificially introduced to reprogram the cell into an ES-like state:
    • Oct3/4
    • Sox2
    • Klf4
    • These ES-like cells are called indiced puripotent stem cells (iPS cells)
    • Cancer
    • Cancer Cells Proliferate, Invade, and Metastasize
    • Cancer cells are defined by two heritable properties:
    • Proliferate in defiance of the normal constraints
    • Just this characteristic results in a benign tumor
    • Invade and colonize territories normally reserved for other cells
    • If the cell has this characteristic, the tumor is cancerous and is said to be malignant
    • They can move to the blood stream and form secondary tumors, or metastasize, at other sites in the body
    • Epidemiology Identifies Preventable Causes of Cancer
    • Epidemiology is the statistical analysis of human populations that is used to look for factors that correlate with disease incidence.
    • Usually where people live governs the type of cancer risks
    • HPV causes uterin cancer
    • Obesity leads to a greater risk of cancer
    • Cancers Develop by an Accumulation of Mutations
    • Cancer is fundamentally a genetic disease
    • Mutagens, agents that cause changes in the nucleotide sequence of DNA
    • Most human cancer cells not only contain many mutations but also are genetically unstable
    • This genetic instability results from mutations that interfere with the accurate replication and maintenance of the genome and thereby increase the mutation rate itself.
    • Cancer Cells Evolve Properties that Give Them a Competitive Advantage
    • Natural selection favors cells carrying mutations that enhance cell proliferation and cell survival regardless of the effects on neighbors
    • A general list of key behaviors of cancer cells distinguish them from normal cells:
    • Reduced dependence on signals from other cells for growth, survival, and division
    • Mutations in the Ras gene can cause intracellular signals for proliferation to be produced even in the absence of extracellular signals
    • Cancer cells are less prone than normal cells to kill themselves by apoptosis
    • About 50% of all human cancers have lost or suffered a mutation in the p53
    • Cancer cells can often proliferate indefinitely
    • Telomerase is not produced so telomeres become too short.
    • Most cancer cells are genetically unstable, with an increased mutation rate
    • Cancer cells are abnormally invasive, mostly due to the lack of cell-adhesion molecules, such as cadherins that hold normal cells in place
    • Cancer cells can often survive and proliferate in foreign tissues to form secondary tumors (metastases), whereas most normal cells die when misplaced.
    • Many Diverse Types of Genes Are Critical for Cancer
    • Oncogene – any abnormally activated gene that can make a cell cancerous. Typically a mutant for of a normal gene (proto-oncogene) involved in the control of cell growth or division
    • Proto-oncogene – the corresponding normal form of the gene
    • For cells, the danger lies in mutations that destroy gene function
    • Tumor suppressor gene – a gene that in a normal tissue cell inhibits progress through the cell cycle. Loss or inactivation of both copies of such a gene from a diploid cell can cause it to divide as a cancer cell.
    • Some of these genes code for growth factors, for receptors, like Ras
    • Others code for DNA repair proteins or mediators like p53
    • Colorectal Cancer Illustrates How Loss of a Gene Can Lead to Growth of a Tumor
    • The abnormlity can be traced to deletion or inactivation of a gene called the Adenomatous Polyposos Coli (APC) gene.
    • Affected individuals inherit one mutant copy of the gene and one normal copy.
    • People with a functioning APC gene have been found to have developed two independent somatic mutations which causes them to develop colon cancer.
    • APC encodes an inhibitory protein that normally restricts the activation of the Wnt signaling pathway, which is involved in stimulating cell proliferation in the crypts of the gut lining as described earlier.
    • An Understanding of Cancer Cell Biology Opens the Way to New Treatments
    • Blocking blood vessels that normally invade a growing tumor.
    • Chronic myeloid leukemia (CML)
    • Gleevac, drug, has been designed to block the activity of this kinase, tyrosine protein kinase, which CML is dependent on.