Biology - Cell communities: Tissues and Stem cells

What are the two broad categories of tissues?

1. Epithelial tissue: like the epidermal covering the skin, cells are tightly bound together into sheet (epithelia), the extracellular matrix is less pronounced we have a basal lamina → cells are attached with cell-cell junctions

2. Connective tissue: like bone, tendons, dermis of the skin, cartilage cells. Sparse and attached to the extracellular matrix

What is the extracellular matrix made of?

• Composed of many fibrous proteins and polysaccharides

• fibrous proteins of the ECM carry the mechanical load

• the matrix can become calcified forming bones and teeth

• influences cell behaviour modulating their: survival, development, migration, proliferation, shape and function

What are the 3 major macromolecules of the ECM?

1. Glycosaminoglycans (GAGs): large and charged polysaccharides covalently linked to a protein to form proteoglycans

2. Fibrous proteins: primarily member of the family of collagen

3. Noncollagen glycoproteins: carry conventional asparagine linked oligosaccharide

What is collagen?

• major protein of ECM

• fibrous protein

• provides tensile strength in animal connective tissue

• made out of alpha chains, 3 alpha chains wrapped around one another to form a triple stranded helical rod

• collagen fibrils are organised into bundles

How does collagen assembly work?

1. Individual polypeptide chain

2. Triple stranded collage molecules

3. Fibrils (bundled into fibres)

4. Fibers

What is the cell called that secretes collagen?

Fibroblast, it secretes collagen and other extracellular matrix components

In what type of collagens is collagen divided ?

1. Collagen fibrils type I

2. Fibril associated collagens

3. Network - forming collagen

How are extracellular molecule produced?

• synthesised intracellularly and then secreted via exocytosis

• outside then they assemble into huge cohesive aggregates

• collagen is synthesised as procollagen that contains unstructured regions → once the pro collagen is secreted extracellular pro collagen proteinases removes the terminal peptides and form mature collagen molecules (this is to prevent fibrils of collagen inside of the cell)

What can incorrect assemble of collagen cause?

Hyperextensible skin

Genetic disorders:

1. lack of enzymes that convert pro collagen into collagen

2. lack in pro collagen itself

What is matrix proteases

It is a proteins that cleaves extracellular proteins, for tissue growth, repair or renewal

What does each kind of cell do with their collagen?

Each kind of cell must correctly align their collagen

1. Skin: woven in alternating layers → to resist tensile stress

2. Tendons: parallel bundles → along major axis of tendon

3. Fibroblasts: control this orientation of collagen by depositing collagen in an ordered fashion and rearranging it

What does elastin do?

• gives the tissue elasticity

• a network of elastic fibres in the ECM give the resistance to recoil after stretch

• long inelast collagen bundles with elastic fibres to limit the extend of the stretching

• precursor is tropoelastin → secreted and then assembled into elastin fibres

• elsatin fibres are joined together by covalent bonds to generate a cross linked network

What do Integrins do ?

They couple the matrix outs to the cytoskeleton inside.

• are transmembrane proteins

• enable cells to make and break attachments to the ECM

• they coordinate the catch and release movement by conformational changes (like cell crawling in a tissue)

What is fibronectin?

It is an ECM glycoprotein

• acts as linker between surface integral molecule and matrix component (collagen)

• when fibronectins and integrals bind to ECM the intracellular domain binds to an actin filament inside the cell

What do Glycosaminoglycans do (GAGs)?

They provide function to resist compression

• negatively charged polysaccharide chains made of repeating disaccharide units

• - charge attracts Na+, which for osmosis brings large amount of H2O unto the matrix

• act as space fillers in ECM

Ex: aggrecan in cartilage is one of the most abundant proteoglycans

WHar are proteoglycans?

Are made of GAG chains covalently linked to a core protein

Characterise the epithelial tissue

• cells organised into epithelia

• joined tightly together

• sheet is many cells thick (epithelia)

• one cell thick (lining of the gut)

Epithelial sheets: are polarised and rest on basal laminated, has 2 faces

1. Apical surface (free and exposed to our bodily fluids)

2. Basal surface (attached to a thin tough sheet of ECM → called basal lamina

What is basal lamina ?

• flexible sheet of matrix molecule

• beneath epithelial cells

• surrounds individual muscle cells, fat cells and Swann cells

• determine cell polarity

What does basal lamina typically contain?

Laminin: is the organiser of the sheet structure

• large family each composed of 3 long polypeptide chains (alpha, beta and gamma)

Type 4 collagen: gives tensile strength

How do cells make junction on lateral parts (where apical parts are exposed)

1. Adherence junction actin

2. tight junctions

3. gap junctions

How do cell make junctions on the basal part?

1. Actin linked cell matrix junction

2. Hemidesmosomes

What are tight junctions

• separate apical and basolateral surface

• make an epithelium leakproof

• prevent apical and basolatera proteins to go to the wrong region

• formed from proteins called:

  1. Cloudins

  2. Occludins

What do anchored junctions do?

• anchoring junctions depend on ltransmemebran adhesion proteins

For example: cytoskeleton junctions bind epithelial cells robustly to one another and to the basal lamina

proteins linking the cytoskeleton fall into two subfamilies:

1. Cadherin (attachment cell-cell)

2. Integrin (link cell to matrix)

What are cell-cell junctions?

• resist external forces

• Catherine forma a diverse family of adhesion molecules (they get their name from their dependence on Ca2+, removing Ca2+ from extracellular medium disrupts adhesion)

• Intracellular domain interacts with filaments on cytoskeleton (actin adherent junctions, and intermediate filaments at desmosomes)

• at adherent junctions Cadherins bind:

  1. Beta-catenin

  2. Alpha-catenin

  3. p120-catenin

• adherence junctions respond to forces generated by actin cytoskeleton

What are desmosomes ?

• links keratin intermediate filaments of one epithelial cell to those of another

• similar to adherence junction but contain non classical cadherin proteins that link to intermediate filament

• these structures give epithelia mechanical strength

What are hemidesmosomes?

• specific type of cell-matrix attachment type in which integrins attach the cell to basal lamina

What are gap junctions?

• couple cells electronically and metabolically

• Chanels that bridge adjacent cells

• allow cytosolic inorganic ions and small molecules to pass from cell-cell

• Formed by:

1. Connexins that form → connexons

• more connexons are present and they flip from an open and closed conformation