Extracellular matrices Flashcards
What is the animal ECM?
All cells assemble an extracellular matrix of macro-molecules. Not just an inert framework. Functions in signalling (perception and transmission). Functions as a co-ordinator of cellular activities (growth and motility and morphogenesis).
Structure of ECM?
What is the basal lamina?
A platform for epithelia and other organised groups of cells (muscles) to rest upon. Tightly bound to the cells by proteins in the plasma membrane.
What is the loose connective tissue?
Highly elastic connective tissue, and bedding on which small glands and epithelia connect to the basal laminae around cells.
What is the dense connective tissue?
Components of skeletal system - bone, cartilage and tendons. Contains few cells, comprised almost entirely of inflexible ECM.
What are the building blocks of animal ECM?
-collagen: protein formed of long fibres or porous sheets -elastin: elastic protein -glycosaminoglycans (GAGs): hyaluronan (long polysaccharide with structure) -proteoglycans: core of protein with attached glycosaminoglycans (GAGs)
What are the structural tensile fibres in the ECM meshwork made of?
Collagen
What is collagen?
An insoluble protein which is the most abundant protein in the animal kingdom.
Three aa per triple helix turn, and every third is GLYCINE. Also rich in proline and hydroxyproline which lends stability to the helix.
Synthesis of collagen?
ER:
- synthesis and translocation of pro α-chain
- proline and lysine hydroxylation: Requires ascorbate
- glycosylation of hydroxylysines
- self-assembly of procollagen triple helix
Golgi:
5. N-linked glycan modifications
Secretory vesicles:
6. transfer to PM
ECM:
- cleavage of propeptides by extracellular proteases
- self-assembly to collagen fibril
- aggregation of fibrils into fibre
Different forms of collagen?
1. Fibril-forming
Importance of different subtypes of fibril-forming collagen seen when mutations cause disease. For example, osteogenesis imperfecta affects type I collagen
2. Fibril-associated – polymerised form has lateral associations. Importance for interaction with other molecules in the ECM. Especially important in cartilage, ligaments and tendon
3. Network-forming – polymerised form has sheet-like network and anchoring fibrils. Three type IV network forming collagen chains form a triple helix with a large globular terminus. GXX sequences are interrupted with non-helix formers, introduces flexibility into the molecule. Type IV collagen molecules assemble into a sheet-like meshwork, rather than rods to help form the basal lamina.
How are benign tumours contained?
Tumour is contained in the cell by the ECM if it is benign, as the tumour begins as a single spontaneously modified cell.
When invasive cells breach the basal laminae of tissue/blood vessels, this leads to a highly invasive metastatic tumour.
How do cells interact with the ECM?
ECM and Actin network are often co-aligned.
Integrins - large class of cell surface receptors that mediate adhesion to the ECM and to other cells. Can bind to different ECM and cellular components (e.g. actin network). Present at focal adhesions.
Integrins form focal adhesions that attach to contractile stress fibres.
In order to crawl over a substrate, the cell must make contact with it. Behind the leading lamellipodium, stress fibres (green) attach to integrins in focal adhesions (orange). Integrins bind to proteins of the extracellular matrix. Myosin-driven (Myosin-II) contraction of the stress fibre pulls the cellular contents forward over the substrate. Contraction at the trailing end also generates hydrostatic pressure.
ECM can orient cells and the underlying cytoskeleton.
ECM plays an essential role in fibroblast differentiation, into bone, fat, smooth muscle or cartilage.
Different ECM components are permissive for neuronal outgrowth.
Basal lamina at neuromuscular junction directs differentiation.
Implications of plant cell wall on growth and functions?
- rigid cell wall defines cell shape
- daughter cells are conjoined at birth by a shared wall
- plant cells generally can’t move or grow past each other
- shape of individual organs is determined solely by growth vectors of individual cells
- growth requires controlled weakening of the wall
Features of the primary plant cell wall?
In young, growing cells.
Flexible and expandable
Formed between cells upon division
Mostly polysaccharide
Features of plant secondary cell wall?
New cell walls are created by cell division within the cell plate. The cell plate divides cells, similar to the actin ring in animal cells.
Plants form two unique microtubule arrays during cell division.
Pre-prophase band disassembles but leaves a mark in the membrane, where the division plane will be.
The Phragmoplast guides the formation of the cell plate. The cell wall forms as the cell plate expands. Golgi derived vesicles carry cell wall polysaccharides to the mid-plane on microtubules.
Develops once cells reach final size. Has greater rigidity and is multi-layered.
Resists biological, chemical and physical attack.
Secondary cell wall microfibrils are thicker and longer than in the primary wall.
Often fortified with lignin. Important in the water transporting xylem vessels. Protects the cell wall during autolysis of the cells. Also protects from collapse under intense negative pressure.
How is cellulose synthesised?
Cellulose is synthesised at the surface of the plasma membrane by multimeric enzymatic terminal complexes – “rosettes”.
Each rosette contains enough CESA proteins to synthesise 18-36 chains which forms a minimal cellulose micro-fibril.
Orientation of cellulose micro-fibril deposition is carefully controlled – determines the growth direction & can limit the extent of cell growth.
Microtubule reorganisation is important in cellulose organisation – mutations that disrupt microtubule organisation disrupt cellulose deposition.
Microtubules guide the deposition of cellulose micro-fibrils. The cellulose polymerisation provides the motive force, no motor proteins involved.
