1. Chapter 20 Notes – Connective Tissues etca. Most cells in mulitcellular organisms are organized into cooperative assemblies called

tissues, such as the nervous, muscle, epithelial, and connective tissues.b. 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.2. Extracellular Matrix and Connective Tissues

i. Strength of a plant tissue comes from the cell walls, formed like boxes that enclose and protect the cells.

b. Plant Cells Have Tough External Wallsi. A primary cell wall usually forms first, which can slowly expand to accommodate

cell growth1. 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.ii. A secondary cell wall forms once cell growth stops

c. Cellulose Microfibrils Give the Plant Cell Wall Its Tensile Strengthi. Cell walls derive their tensile strength from cellulose.

1. Synthesized on the outside of the cell by enzyme complexes in the PMa. Complexes transport sugar monomers across the PM and incorporate

them into a set of growing polymer chains at their points of membrane attachment.

i. Each set of chain forms a cellulose microfibril.ii. 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

ii. Cellulose microfibrils are interwoven with other polysaccharides and some structural proteins, all bonded together to form a complex structure that resists compression and tension.

iii. Lignin – usually in woody tissue, is deposited within the matrix to make it more rigid and waterproof.

iv. Cellulose will not stretch, so the oriv. entation of the cellulose in the cell will determine in which direction it will grow.

d. Animal Connective Tissues Consist Largely of Extracellular Matrixi. There are four major types of tissues in animals

1. Connectivea. ECM is plentiful and carries mechanical loadb. 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.i. Bullk of this is a fibrous protein called collagen.

2. Epitheliala. ECM is little and cells are directly adhered to one another and carry

mechanical load themselves.3. Nervous4. Muscular

e. Collagen Provides Tensile Strength in Animal Connective Tissuesi. Collagens are the chief proteins in bon, tendon, and skin and they constitute for

about 25% of the total proteins in mammalsii. 3 collagen polypeptide chains are wound around one another in a rope-like helix

1. assemble into ordered polymers called collagen fibrils

a. pack together into thicker collagen fibersiii. 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

1. Fibroblasts a. Skin, tendons, and other connective tissue

2. Osteoblastsa. Bone

iv. Synthesized internally and transported via exocytosisv. Cells secrete procollagen first, which obstruct assembly to collagen fibrils so the cell

doesn’t choke itself in its own product1. Procollagen proteinases cut terminal of terminal domains to allow assembly

only after the molecules are in the EXSa. Mutations result in less tensile strength in skin and stretchability

vi. Cells in tissue must degrade matrix as well as make for tissue growth, repair, and renewal.

f. Cells Organize the Collagen That They Secretei. Connective-tissue cells control the orientation of the collagen

1. Deposit collagen in oriented fashiona. Rearrange it

ii. Fibroblasts shape collagen they secrete1. If in culture where collagen is disorganized, fibrolasts tug on the meshwork

and compact it2. Fibroblasts are important for healing wounds

g. Integrins Couple the Matrix Outside a Cell to the Cytoskeleton Inside Iti. Fibronectin provides a linkage for cells to crawl over one another.

1. One part of fibronectin binds to collagen, while another forms an attachment site for a cell.

a. The binding site of a cell is a receptor protein called integrin, which spans the cell’s PM and binds to fibronectin

i. Integrin’s intracellular domain binds to actin filaments inside the cell.

ii. 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

1. An intracellular signal can activate the integrin causing it to reach out and grab hold of an extracellular structure

a. Binding to an extracellular structure can activate intracellular signaling cascades via protein kinases that associate with the intracellular end of the integrin.

ii. Leucocyte adhesion deficiency1. When integrins on WBCs cannot help a cell crawl out of blood vessels at

sites of infectioniii. Individuals lacking integrins in blood platelets cannot clot blood and bleed

excessivelyh. Gels of Polysaccharide and Protein Fill Spaces and Resist Compression

i. Proteoglycans 1. EXC proteins linked to a special class of negatively charged polysaccharides,

glycosaminoglycans (GAGs)a. Dense, compact, connective tissues such as tendons and bones, the

proportion of GAGs is small and the matrix is almost all collagenb. Jellylike substance in the eye consist of almost only one type of GAG,

plus water, with only a small amount of collagen.2. Strongly hydrophilic which provides hydrate space in around cells3. Negative charges attract ions4. Osmotically active, causing large amounts of water to be sucked into the

matrix, causing swelling balanced by tension in collagen fibers interwoven with proteoglycans.

a. Cartilage matrix of knee joint is hugely tough5. Help resist compression6. Can make gels of densities that help filter molecules7. Bind secreted GFs and other proteins that serve as signals for the cells.8. Can guide cell movement through matrix

3. Epithelial Sheets and Cell Junctionsi. Epithelium – sheet of cells covering an external surface or lining an internal body

cavity1. Can be stratified or simple epithelium, only one cell layer like the gut

ii. Epithelia cover the external surface of the body and line all its internal cavities.iii. Cells joined in sheet create a barrier that has the same significance of the PM of

cells.b. Epithelial Sheets Are Polarized and Rest on a Basal Lamina

i. Epithelial sheets have two faces:1. Apical surface

a. Free and exposed to air or watery fluid2. Basal surface

a. Rests on some other tissue, usually connective, to which it is attachedb. 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.

ii. Absorptive cells, which take up nutrients, and goblet cells, which secrete mucus, in the intestines

c. Tight Junctions Make an Epithelium Leak-Proof and Separate Its Apical and Basal Surfacesi. Cell junctions – Specialized region of connection between two cells or between a

cell and the ECMii. Tight Junctions

1. Seal neighboring cells together so the water-soluble molecules cannot easily leak between them.

2. Formed from claudin and occluding proteins, which are arranged in strands along the lines of junctions to create seals.

3. Without, the pumping activities of apsorptive cells would be futile and the concentration on both sides of the epithelium would be the same

4. 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.

5. TJs are sites of assembly for the complexes of intracellular proteins that fovern apico-basal polarity in the interior of the cell.

d. Cytoskeleton-linked Junctions Bind Epithelial Cells Robustly to One Another and to the Basal Lamina

i. There are three types of junctions that hold an epithelium together by forming mechanical attachments:

1. Adherens junctions (and Desmosomes)a. Bind one epithelial cell to anotherb. Built around transmembrane proteins that belong to the cadherin

familyi. A cadherin molecule in the PM of one cell sinds directly to an

identical cadherin molecule in the PM of its neighbor.1. Such binding of like to like is called homophilic binding.2. In the case of cadherins, binding also requires that

Ca2+ be present in the EXC medium – hence its namec. Adherens Junction

i. Each cadherin molecule is tethered inside its cell, via several linker proteins, to actin filaments.

ii. 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.

iii. By shrinking the apical surface along one axis, the sheet can roll itself up into a tube.

1. Or it can make a cup-shaped concavity and eventually create a vesicle that may pinch off from the rest of the epithelium

d. Desmosomes i. These cadherins connect to intermediate filamets –

specifically to keratins, which are the types of intermediate filaments found in epithelia

2. Hemidesmosomesa. Bind epithelial cells to the basal laminab. Attachments of epithelial cells to the extracellular matrix beneath

themii. The molecule that forms the external adhesion spans the membrane and is linked

inside the cell to strong cytoskeletal filamentse. Gap Junctions Allow Ions and Small Molecules to Pass from Cell to Cell

i. Another type of epithelial cell junctionii. 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.1. Connexons form the channels across two PMs and allow inorganic ions and

small water-soluble molecules to move directly from cytosol to cytosol.a. Creates an electrical and metabolic coupling between the cells.b. GJs in heart muscle cells proved electrical coupling that allows

electrical waves of excitation to spread through the tissue.

i. These waves trigger the coordinated contraction of the cells, producing a regular heart beat.

2. Can be opened or closed as needed in response of extracellular signals.a. Dopamine, a neurotransmitter, reduces GJ communication within a

class of neurons in the retina in response to an increase in light intensity.

i. 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.

iii. Plasmodesmata in plant cells are the functional couterpart of GJs1. Cytoplasmic channels lined with PM, and the cytoplasm becomes continuous

form one cell to the next.4. Tissue Maintenance and Renewal

a. Tissues Are Organized Mixtures of Many Cell Typesi. All tissues need mechanical strength, which is often supported by a supporting bed

or framework of connective tissue inhabited by fibroblasts1. In the connective tissue blood cells lined with endothelial cells supply

oxygen, nutrients and waste disposalii. Three main factors contribute to the stability and organization of tissues:

1. Cell communicationa. Social signals from other cellsb. Live and die when required

2. Selective cell-cell adhesiona. Cells have different cadherins and adhesion molecules , so the stick

selectively by homophilic bindingb. Selectivity of adhesion prevents mixing of tissue types.

3. Cell memorya. Patterns of gene expressionb. Only cells of a type divide to form another cell of the same type

b. Different Tissues Are Renewed at Different Ratesi. Nerve cells usually last a lifetime

ii. Intestinal lining cells replaced every few daysiii. Bone replaces roughly every ten years in humans

1. Old bone matrix is eaten by osteoclasts2. Osteoblasts deposit new matrix

iv. RBCs are generated in the marrow and last 120 daysv. Skin is replaced every two months

c. Stem Cells Generate a Continuous Supply of Terminally Differentiated Cellsi. Terminally differentiated cells lie at the end of their developmental pathway

ii. Proliferating precursor cells are replacements for TD cells.1. Derive from stem cells

a. Can divide without limiti. Divides to another stem cell and then to a TD cell

2. RBCs derive from a hemopoietic stem cell found in the bone marrowd. Specific Signals Maintain the Stem-Cell Populations

i. Signals are from the stem cells themselves, progeny, and surrounding tissues

ii. 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.

e. Stem Cells Can Be Used to Repair Damaged Tissuesi. Embryonic stem cells (ES cells)

1. Can proliferate indefinitely in culture and retain unrestricted developmental potential and are thus said to be pluripotent

2. Can maybe one day be used to grow full organsa. Problem: if the cells are genetically different, they may be detected

and destroyed by the immune system, but therapeutic cloning could prevent this.

f. Therapeutic Cloning Could Provide a Way to Generate Personalized ES Cellsi. Reproductive cloning – the cloning of entire multicellular animals

ii. 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

iii. Genes artificially introduced to reprogram the cell into an ES-like state:1. Oct3/42. Sox23. Klf44. These ES-like cells are called indiced puripotent stem cells (iPS cells)

5. Cancera. Cancer Cells Proliferate, Invade, and Metastasize

i. Cancer cells are defined by two heritable properties:1. Proliferate in defiance of the normal constraints

a. Just this characteristic results in a benign tumor2. Invade and colonize territories normally reserved for other cells

a. If the cell has this characteristic, the tumor is cancerous and is said to be malignant

i. They can move to the blood stream and form secondary tumors, or metastasize, at other sites in the body

b. Epidemiology Identifies Preventable Causes of Canceri. Epidemiology is the statistical analysis of human populations that is used to look

for factors that correlate with disease incidence.1. Usually where people live governs the type of cancer risks

ii. HPV causes uterin canceriii. Obesity leads to a greater risk of cancer

c. Cancers Develop by an Accumulation of Mutationsi. Cancer is fundamentally a genetic disease

ii. Mutagens, agents that cause changes in the nucleotide sequence of DNAiii. Most human cancer cells not only contain many mutations but also are genetically

unstable1. This genetic instability results from mutations that interfere with the

accurate replication and maintenance of the genome and thereby increase the mutation rate itself.

d. Cancer Cells Evolve Properties that Give Them a Competitive Advantagei. Natural selection favors cells carrying mutations that enhance cell proliferation and

cell survival regardless of the effects on neighborsii. A general list of key behaviors of cancer cells distinguish them from normal cells:

1. Reduced dependence on signals from other cells for growth, survival, and division

a. Mutations in the Ras gene can cause intracellular signals for proliferation to be produced even in the absence of extracellular signals

2. Cancer cells are less prone than normal cells to kill themselves by apoptosisa. About 50% of all human cancers have lost or suffered a mutation in

the p533. Cancer cells can often proliferate indefinitely

a. Telomerase is not produced so telomeres become too short.4. Most cancer cells are genetically unstable, with an increased mutation rate5. Cancer cells are abnormally invasive, mostly due to the lack of cell-adhesion

molecules, such as cadherins that hold normal cells in place6. Cancer cells can often survive and proliferate in foreign tissues to form

secondary tumors (metastases), whereas most normal cells die when misplaced.

e. Many Diverse Types of Genes Are Critical for Canceri. 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

ii. Proto-oncogene – the corresponding normal form of the geneiii. For cells, the danger lies in mutations that destroy gene function

1. 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.

a. Some of these genes code for growth factors, for receptors, like Rasb. Others code for DNA repair proteins or mediators like p53

f. Colorectal Cancer Illustrates How Loss of a Gene Can Lead to Growth of a Tumori. The abnormlity can be traced to deletion or inactivation of a gene called the

Adenomatous Polyposos Coli (APC) gene.1. Affected individuals inherit one mutant copy of the gene and one normal

copy.2. People with a functioning APC gene have been found to have developed two

independent somatic mutations which causes them to develop colon cancer.3. 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.

g. An Understanding of Cancer Cell Biology Opens the Way to New Treatmentsi. Blocking blood vessels that normally invade a growing tumor.

ii. Chronic myeloid leukemia (CML)1. Gleevac, drug, has been designed to block the activity of this kinase, tyrosine

protein kinase, which CML is dependent on.