Ch 20 - Cell Communities: Tissues, Stem Cells, & Cancer

Extracellular matrix

material that cells secrete around themselves
this matrix gives supportive tissues such as bone or wood their strength

In plants, the supportive matrix is the

cell wall
boxlike structure that encloses, protects, immobilizes, and shapes each cell

Plant tissues are strengthened by

cell walls!!

Plant cells themselves synthesize, secrete, and control the composition of this extracellular matrix

cell wall
a cell wall can be thick and hard, as in wood
or thin and flexible, as in a leaf

The plant cytoskeleton lacks the tension-bearing intermediate filaments found in animal cells, and virtually has no

tensile strength

Most newly formed cells in a plant initially make relatively thin primary cell walls, which can slowly expand to accommodate

cell growth

The driving force for cell growth is the same as that keeping the lettuce leaf crisp - a swelling pressure called

turgor pressure that develops as the result of an osmotic imbalance between the interior of the plant cell and its surroundings

Once cell growth stops and the wall no longer needs to expand, a more rigid

secondary cell wall is often produced, either by thickening of the primary wall or by deposition of new layers with a different composition underneath the old ones

When plant cells become specialized, they produce specially adapted types of

walls: waxy, waterproof walls for the cells of a leaf; hard, thick, woody walls for the xylem cells of the stem

A cellulose microfibril is made from

a bundle of cellulose molecules
- cellulose molecules are long, unbranched chains of glucose
- each glucose subunit is inverted with respect to its neighbors and joined via B1, 4-linkage

Cellulose microfibrils give the plant cell wall its

tensile strength
Plant cell walls derive their tensile strength from long fibers oriented along the lines of stress

Long fibers are generally made from the polysaccharide cellulose

these cellulose microfibrils are interwoven with other polysaccharides and some structural proteins
all bonded together to form a complex structure that resists both compression and tension
- Lignin is deposited within this matrix to make it more rigid and waterproof

Primary plant cell wall:

- cellulose microfibrils provide tensile strength
- other polysaccharides cross-link the cellulose microfibrils, while the polysaccharide pectin fills the spaces between the microfibrils, providing resistance to compression
- the middle lamella is rich in pectin and is the layer that cements one cell wall to another

For a plant cell to grow or change its shape, the cell wall has to

stretch or deform
cellulose microfibrils resists stretching, so their orientation governs the direction in which the growing cell enlarges

Cellulose is synthesized on the outer surface of the cell by

enzyme complexes embedded in the plasma membrane
- these complexes transport glucose monomers from the cytosol across the plasma membrane and incorporate them into a set of growing cellulose chains at their points of membrane attachment
- resulting cellulose chains assemble to form a cellulose microfibril

Microtubules direct the enzyme complexes beneath

the plasma membrane

The orientation of cellulose microfibrils within the plant cell wall influences the

direction in which the cell elongates
each cell tends to elongate in a direction perpendicular to the orientation of the microfibrils, which have great tensile strength

Microtubules help direct the deposition of cellulose in the plant cell wall

the cortical array of microtubules attached to the plasma membrane by transmembrane proteins helps determine the direction in which the microfibrils are laid down

Animal connective tissues consist largely of

extracellular matrix

Four major types of tissues in animals

connective, epithelial, nervous, and muscular

Connective tissue:

extracellular matrix is abundant and carries the mechanical load
bone

In other tissues, such as epithelia:

extracellular matrix is sparse and the cells are directly joined to one another and carry the mechanical load themselves

Elastin

gives the walls of arteries their resilience as blood pulses through them

Collagen provides tensile strength in

animal connective tissues

Collagens

family of proteins that come in many varieties
main proteins in bone, tendon, skin
type I collagen is the most abundant and accounts for 90% of the body's collagen

Characteristics of collagen:

- long, stiff, triple stranded helical structure
- three collagen polypeptide chains are wound around one another in a ropelike superhelix
- some types of collagen molecules assemble into ordered polymers called collagen fibrils (thin cables)
- can pack together into thicker collagen fibers

Fibroblasts

the connective tissue cells that manufacture and inhabit the extracellular matrix
in bone, they are called osteoblasts
- these cells make both the collagen and other macromolecules of the matrix
- synthesized intracellularly and then secreted by exocytosis
- outside the cell, they assemble into huge, cohesive aggregates

If assembly were to occur before secretion, the cell would become

choked with its own products
to avoid this, cells secrete precursor form of collagen molecules - procollagen

Procollagen

has additional peptide extensions at each end that obstruct premature assembly into collagen fibrils
- extracellular enzymes called procollagen proteinases cut off these terminal extensions to allow assembly only after the molecules have emerged into the extracellular space

Procollagen precursors are cleaved to form mature collagen outside the cell

- collagen is synthesized as procollagen, with unstructured peptides at either end
- these peptides prevent collagen fibrils from assembling inside the fibroblast
- when the procollagen is secreted, extracellular procollagen proteinases remove its terminal peptides, produce mature collagen molecules
- these molecules can then self-assemble into ordered collagen fibrils

Incorrect collagen assembly can cause the skin to be

hyperextensible

Integrins couple the matrix outside a cell to the

cytoskeleton inside it

The extracellular domain of an integrin binds to components of the matrix, while its intracellular domain interacts with

the cell cytoskeleton

Integrins do not interact directly with collagen fibers in the extracellular matrix

fibronectin instead provides a linkage: part of the fibronectin molecule binds to collagen, while another part forms an attachment site for integrins
- when the extracellular domain of the integrin binds to fibronectin, the intracellular domain binds to an actin filament inside the cell

Binding to a molecule on one side of the plasma membrane causes the integrin molecule to

stretch out to an extended, activated state so that it can then latch onto a different molecule on the opposite side
- "catch and release"
- an intracellular signaling molecule can activate the integrin from the cytosolic side, causing it to reach out and grab hold of an extracelllular structure

Fibroblasts influence the alignment of

collagen fibers

Fibronectin and transmembrane integrin proteins help attach a cell to the

extracellular matrix

An integrin protein switches to an active conformation when it binds to molecules on either side of the plasma membrane

- integrin protein contains two different subunits (a and B) both of which can switch between a folded, inactive form and an extended, active form
- the switch to an activated state can be triggered by binding to an extracellular matrix molecule or to intracellular adaptor proteins that then link the integrin to the cytoskeleton

Glycosaminoglycans (GAGs)

resists compression
negatively charged polysaccharide chains made of repeating disaccharide units

Chains of GAGs are usually covalently linked to

a core protein to form proteoglycans, which are extremely diverse in size, shape, and chemistry
many GAG chains are attached to a single core protein that may be linked to another GAG

In dense, compact connective tissues such as tendon and bone, the proportion of GAGs is

small, and the matrix consists almost entirely of collagen

The eye consists almost entirely of one particular type of

GAG, plus water, with only a small amount of collagen

GAGs are strongly hydrophilic and tend to adopt

highly extended conformations, which occupy a huge volume relative to their mass
- GAGs act as effective space fillers in the extracellular matrix of connective tissues

Proteoglycans and GAGs can form

large aggregates

Even at very low concentrations, GAGs form hydrophilic gels

their multiple negative charges attract clouds of cations such as Na+, that are osmotically active, causing large amounts of water to be sucked into the matrix

When the matrix is rich in collagen and large quantities of GAGs are trapped in the mesh, both the swelling pressure and counterbalancing tension are

enormous
this matrix is tough, resilient, and resistant to compression
ex: knee joint

Proteoglycans

provide hydrating space around cells
- can form gels of varying pore size and density that act as filters to regulate the passage of molecules through the extracellular medium
- can bind to secreted growth factors
- can block, encourage, or guide cell migration through the matrix

Epithelia are

multicellular sheets in which adjacent cells are joined tightly together
the sheet is many cells thick (stratified) as in the epidermis
simple epithelium (only one cell thick) as in the lining of the gut
- Epithelia cover the external surface of the body and line all its internal cavities

Epithelial sheets are polarized and rest on

a basal lamina

A sheet of epithelial cells has an

apical and a basal surface
- the apical surface that is free and exposed to the air or body fluid
- the basal surface that is attached to a sheet of connective tissue (basal lamina)

Basal lamina

consists of a thin, tough sheet of extracellular matrix, composed mainly of a specialized type of collagen (type 4) and a protein called laminin

Laminin

provides adhesive sites for integrin molecules in the basal plasma membranes of epithelial cells
serves a linking role

Tight junctions make an epithelium leakproof and separate its

apical and basolateral surfaces

Cell junctions can be classified according to their function

some provide a tight seal to prevent leakage of molecules
some provide strong mechanical attachments
some provide a type of intercytosolic exchange
all are present in epithelia

The barrier function of epithelial sheets is made possible by

tight junctions
seal neighboring cells together so the water-soluble molecules cannot easily leak between them

Tight junction is formed from proteins called

claudins and occludins, which are arranged in strands along the lines of the junction to create the seal

Tight junctions allow epithelial sheets to serve as barriers to solute diffusion

claudins and occludins - transmembrane proteins that seal together the cells in the plasma membrane of the interacting cells

Different types of functionally polarized cell types line the intestine

absorptive cells (take up nutrients from the intestine) are mingled in the gut epithelium with goblet cells, which secrete mucus into the gut lumen
- the absorptive cells contain microvilli on the apical surface
- microvilli increase the are of apical plasma membrane for the transport of small molecules into the cell

Tight junctions also maintain the polarity of the individual epithelia cells

- the tight junctions around the apical region of each cell prevent diffusion of proteins in the plasma membrane and keep the contents of the apical domain separate from the basolateral domain
- the tight junctions are sites of assembly for the complexes of intracellular proteins that govern the apico-basal polarity of the cell interior

Cytoskeleton-linked junctions bind epithelial cells robustly to

one another and to the basal lamina

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

- adherens junctions
- desmosomes
- both bind one epithelial cell to another
- hemidesmosomes - bind epithelial cells to the basal lamina
all of these junctions provide mechanical strength to the epithelium by the same strategy: the proteins that form the junctions span the plasma membrane and are linked inside the cell to cytoskeletal filaments

Adherens junctions and desmosomes are both built around transmembrane proteins that belong to the

cadherin family

Cadherin proteins mediate mechanical attachment of one cell to another

identical cadherin molecules in the plasma membranes of adjacent cells bind to each other extracellularly
inside the cell, they are attached via linker proteins to cytoskeletal filaments (either actin filaments or keratin intermediate filaments)

A cadherin molecule in the plasma membrane of one cell binds directly to

an identical cadherin molecule in the plasma membrane of its neighbor
called homophilic binding
binding also requires Ca2+ to be present in the extracellular medium

At an adherens junction, each cadherin molecule is

tethered inside its cell via several linker proteins to actin filaments

Desmosome

different set of cadherin molecules connects to keratin filaments (the intermediate filaments found specifically in epithelial cells)

Adheren junctions form adhesion belts

around epithelial cells in the small intestine
a contractile bundle of actin filaments runs along the cytoplasmic surface of the plasma membrane near the apex of each cell
these bundles are linked to those in adjacent cells via transmembrane cadherin molecules

Epithelial sheets can bend to form an

epithelial tube or vesicle
contraction of apical bundles of actin filaments linked from cell to cell via adherens junctions causes the epithelial cells to narrow at their apex

Desmosomes link the keratin filaments of

one epithelial cell to those of another

Hemidesmosomes anchor the

keratin filaments in an epithelial cell to the basal lamina
the linkage is mediated by a transmembrane attachment complex containing integrins, rather than cadherins

Epidermal cells must be anchored to the

underlying connective tissue
- the anchorage is mediated by integrins in the cells' basal membranes
- extracellular domains of these integrins bind to laminin in the basal lamina
- inside the cell, the integrin tails are bound via linker proteins to keratin filaments, creating a structure that looks like half a desmosome

Attachments of epithelial cells to the basal lamina beneath them are called

hemidesmosomes

Gap junctions allow

cytosolic inorganic ions and small molecules to pass from cell to cell
directly from the cytosol of one cell to the cytosol of the other
flow creates an electrical and metabolic coupling between the cells

Gap junctions

- regions where the plasma membranes of two cells lie close together and exactly parallel, with a very narrow gap between them
- gap is spanned by the protruding ends of many identical, transmembrane protein complexed that reside in the plasma membranes of the two appposed cells
- these complexes (connexons) are aligned end to end to form narrow, water-filled channels across the interacting membranes

Gap junctions can be opened or closed in response to

extracellular or intracellular signals

Gap junctions provide neighboring cells with

a direct channel of intercytosolic communication

Tight junctions

seals neighboring cells together in an epithelial sheet to prevent leakage of extracellular molecules between them; helps polarize cells

Adherens junctions

joins an actin bundle in one cell to a similar bundle in a neighboring cell

Desmosome

joins the intermediate filaments in one cell to those in a neighbor

Gap junction

forms channels that allow small, intracellular, water soluble molecules, including inorganic ions and metabolites, to pass from cell to cell

Hemidesmosome

anchors intermediate filaments in a cell to basal lamina

Plant tissues lack all the types of cell junctions discussed, but they have a sort of gap junction called

plasmodesmata

Plasmodesmata

connect the cytoplasms of adjacent plant cells
communicating channels that span the intervening cell walls, lined with plasma membrane

In plants, the cytoplasm is

continuous from one cell to the next, allowing the passage of both small and large molecules

Three main factors contribute to this stability of tissues:

1. cell communication - each type of specialized cell continuously monitors its environment for signals from other cells and adjusts its behavior accordingly
this communication ensures that new cells are produced and survive only when and where they are required
2. selective cell adhesion - cells tend to stick selectively by homophilic binding to other cells of the same type
may also form selective attachments to certain other cell types and to specific extracelllular matrix components. the selectivity keeps ceels in their proper positions
3. cell memory - specialized patterns of gene expression, evoked by singals that acted during embryonic development, are afterward stably maintained so that cells preserve their distinctive character and pass it on to their progeny

Tissues are organized mixtures of

many cell types

Different tissues are renewed at

different rates
- Bone has a turnover time of about 10 years
old bone is slowly eaten away by a set of cells called osteoclasts
osteoblasts deposit new matrix
- Epithelium is replaced every 3-6 days

Stem cells and proliferating precursor cells generate a continuous supply of

terminally differentiated cells

Terminally differentiated cells

- specialized
- need continual replacement, unable to divide
ex: RBCs, epidermal cells in upper layers of the skin, absorptive and goblet cells of the gut epithelium
terminally differentiated - they lie dead end of their developmental pathway

The cells that replace the terminally differentiated cells that are lost are generated from

a stock of proliferating precursor cells, which themselves usually derive from a much smaller number of self-renewing stem cells
stem cells are not differentiated and can divide without a limit

When a stem cell divides, each daughter can either

remain a stem cell (self-renewal) or go on to become terminally differentiated
- terminally differentiated cells usually develop from proliferating precursor cells that divide a limited number of times before they terminally differentiate
- stem-cell divisions can also produce two stem cells or two precursor cells, as long as a pool of stem cells is maintained

Stem cells function:

to produce cells that will carry out specialized function

Both stem cells and proliferating precursor cells are usually retained in

their resident tissue along with their differentiated progeny cells

Epithelium (lining) in the small intestine

single layered, covering the surfaces with villi
- this epithelium is continuous with the epithelium lining the crypts, which descends into the underlying connective tissue
- the stem cells lie near the bottom of the crypts, where they give rise mostly to proliferating precursor cells, which move upward in the plane of the epithelial sheet
- as they move upward, the precursor cells terminally differentiate into absorptive or secretory cells, which are shed into the gut lumen and die when they reach the tips of the villi

In the stratified epithelium, the stem cells and precursor cells are confined to the

basal layer, adhering to the basal lamina

A single type of stem cell gives rise to

several types of differentiated progeny:
stem cells in the intestine produce absorptive cells, goblet cells, and several other secretory cell types

Hemopoiesis

process of blood-cell formation
A hemopoietic stem cell divides to generate more stem cells, as well as various types of precursor cells that proliferate and differentiate into the mature blood cell types found in the circulation

Wnt proteins

class of signal molecules
- serves to promote the proliferation of the stem cells and precursor cells at the base of each intestinal crypt
- cells in the crypt produce other signals that act as longer range to prevent activation of the Wnt pathway outside crypts

The Wnt signaling pathway maintains the

proliferation of the stem cells and precursors cells in the intestinal crypt
- the Wnt proteins are secreted by cells in and around the crypt base, especially by the Paneth cells - a subclass of terminally differentiated secretory cells that are generated from the gut stem cells
- newly formed Paneth cells, which move down to the crypt bottom instead of up to the tip of the villus have a dual function: they secrete antimicrobial peptides to keep infection at bay and provide signals to sustain the stem cell population

Stem cells can be used to repair lost or damaged tissues

Because stem cells can proliferate indefinitely and produce progeny that differentiate, they provide for both continual renewal of normal tissue and repair of tissue lost through injury