1.

Chapter 20 Notes Connective Tissues etc

a. 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 Walls
i. A primary cell wall usually forms first, which can slowly expand to accommodate
cell growth
1. 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 Strength
i. Cell walls derive their tensile strength from cellulose.
1. Synthesized on the outside of the cell by enzyme complexes in the PM
a. 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 ori
v. entation of the cellulose in the cell will determine in which direction it will grow.
d. Animal Connective Tissues Consist Largely of Extracellular Matrix
i. There are four major types of tissues in animals
1. Connective
a. ECM is plentiful and carries mechanical load
b. 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. Epithelial
a. ECM is little and cells are directly adhered to one another and carry
mechanical load themselves.
3. Nervous
4. Muscular
e. Collagen Provides Tensile Strength in Animal Connective Tissues
i. Collagens are the chief proteins in bon, tendon, and skin and they constitute for
about 25% of the total proteins in mammals
ii. 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 fibers
iii. 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. Osteoblasts
a. Bone
iv. Synthesized internally and transported via exocytosis
v. Cells secrete procollagen first, which obstruct assembly to collagen fibrils so the cell
doesnt choke itself in its own product
1. Procollagen proteinases cut terminal of terminal domains to allow assembly
only after the molecules are in the EXS
a. 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 Secrete
i. Connective-tissue cells control the orientation of the collagen
1. Deposit collagen in oriented fashion
a. Rearrange it
ii. Fibroblasts shape collagen they secrete
1. If in culture where collagen is disorganized, fibrolasts tug on the meshwork
and compact it
2. Fibroblasts are important for healing wounds
g. Integrins Couple the Matrix Outside a Cell to the Cytoskeleton Inside It
i. 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 cells PM and binds to fibronectin
i. Integrins 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 deficiency
1. When integrins on WBCs cannot help a cell crawl out of blood vessels at
sites of infection
iii. Individuals lacking integrins in blood platelets cannot clot blood and bleed
excessively
h. 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 collagen
b. 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 cells
3. Negative charges attract ions
4. 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 tough
5. Help resist compression
6. Can make gels of densities that help filter molecules
7. 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 Junctions
i. Epithelium sheet of cells covering an external surface or lining an internal body
cavity
1. 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 fluid
2. Basal surface
a. Rests on some other tissue, usually connective, to which it is attached
b. 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 Surfaces
i. Cell junctions Specialized region of connection between two cells or between a
cell and the ECM
ii. 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 another
b. Built around transmembrane proteins that belong to the cadherin
family
i. 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 name
c. 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. Hemidesmosomes
a. Bind epithelial cells to the basal lamina
b. Attachments of epithelial cells to the extracellular matrix beneath
them
ii. The molecule that forms the external adhesion spans the membrane and is linked
inside the cell to strong cytoskeletal filaments
e. Gap Junctions Allow Ions and Small Molecules to Pass from Cell to Cell
i. Another type of epithelial cell junction
ii. 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 GJs
1. 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 Types
i. All tissues need mechanical strength, which is often supported by a supporting bed
or framework of connective tissue inhabited by fibroblasts
1. In the connective tissue blood cells lined with endothelial cells supply
oxygen, nutrients and waste disposal
ii. Three main factors contribute to the stability and organization of tissues:
1. Cell communication
a. Social signals from other cells
b. Live and die when required
2. Selective cell-cell adhesion
a. Cells have different cadherins and adhesion molecules , so the stick
selectively by homophilic binding
b. Selectivity of adhesion prevents mixing of tissue types.
3. Cell memory
a. Patterns of gene expression
b. Only cells of a type divide to form another cell of the same type
b. Different Tissues Are Renewed at Different Rates
i. Nerve cells usually last a lifetime
ii. Intestinal lining cells replaced every few days
iii. Bone replaces roughly every ten years in humans
1. Old bone matrix is eaten by osteoclasts
2. Osteoblasts deposit new matrix
iv. RBCs are generated in the marrow and last 120 days
v. Skin is replaced every two months
c. Stem Cells Generate a Continuous Supply of Terminally Differentiated Cells
i. 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 limit
i. Divides to another stem cell and then to a TD cell
2. RBCs derive from a hemopoietic stem cell found in the bone marrow
d. 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 Tissues
i. 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 organs
a. 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 Cells
i. 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. Oct3/4
2. Sox2
3. Klf4
4. These ES-like cells are called indiced puripotent stem cells (iPS cells)
5. Cancer
a. 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 tumor
2. 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 Cancer
i. 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 cancer
iii. Obesity leads to a greater risk of cancer
c. Cancers Develop by an Accumulation of Mutations
i. Cancer is fundamentally a genetic disease
ii. Mutagens, agents that cause changes in the nucleotide sequence of DNA
iii. Most human cancer cells not only contain many mutations but also are genetically
unstable
1. 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 Advantage
i. Natural selection favors cells carrying mutations that enhance cell proliferation and
cell survival regardless of the effects on neighbors
ii. 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 apoptosis
a. About 50% of all human cancers have lost or suffered a mutation in
the p53
3. 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 rate
5. Cancer cells are abnormally invasive, mostly due to the lack of cell-adhesion
molecules, such as cadherins that hold normal cells in place
6. 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 Cancer
i. 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 gene
iii. 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 Ras
b. 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 Tumor
i. 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 Treatments
i. 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.