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MOLECULAR AND CELL BIOLOGY - Coggle Diagram
MOLECULAR AND CELL BIOLOGY
Microenvironment
Not just chemical but also physical
Heat, tension, pressure, E field
Laminar flow and endothelial cells
The cells also interact with each other because they are connected to each other.
Different matrix and signalling proteins
Meshwork
Does the cell really need both?
3D
Many of the studies are done in 2D.
Can recruit things like growth factors, and influence the biochemistry
Things move at various rates
ECM restricts cell spreading in 3D
Neighbouring cells
Angiogenesis
Autoregulation and niche formation
ECM
Gene expression; every cell in the body has the same genes
Highly subtly regulated
The same ligand in liquid and trapped form may elicit different responses
Proteins making it up
Fibrous proteins
Collagen
Most abundant fibrous protein
There exist multiple types
Most form a triple stranded helix
May associate to form fibrils and networks, depending on the type of collagen
Collagen fibril in CT
Networks in BM
Structure
Type 1
Hydroxylation
Glycosylation
Lysyl Oxidases crosslink after all the post translational modifications
Usually one type mostly per tissue
Functions
Tensile strength
Cell adhesion
Chemotaxis and migration
Regulate development
Made by fibroblasts
In the matrix
From surrounding tissue
Put tension on the matrix and therefore affect collagen orientation into bundles and sheets
Fibronectin
Secreted as a dimer
The two polypeptide chains are similar but generally not identical different RNA splices
Several binding sites
Other FN domains
Collagen
Heparin
Integrin
RGD
Can change the density of the ECM by stretching
Cytoskeleton and ECF integration by contraction
Laminin
Elastin
gives recoil to tissues
ECM receptors on cells
Integrins
Discoidin Domain Receptors
Syndecans
Resp for the biomechanics of the tissue
Proteoglycans are made up of GAGs
Types
Small Leucine Rich
Modular
Cell surface
Hydrophilic very
Therefore form gels that allow for shock absorption
Fill up the interstitium
Egs of functions
In the glomerular BM,
perlecan
helps in ultrafiltration
In ductal epithelial tissues,
decorin, biglycan and lumican
associate with collagen fibres to generate a molecular structure within the ECM that is essential for
mechanical buffering and hydration
and that, by
binding GFs
, provides an easy, enzymatically accessible repository for these factors
Alterations in disease
Ageing
Scar tissue
Tumours
Wounds that don't heal
Stiffening
Cell ECM adhesion
Functions
Organogenesis
Maintaining organ integrity
Alterations may cause disease
External binding to ECM, internal binding to cytoskeleton
Outside in signalling
Inside out signalling: Internal ligands can cause changes to the structure of ligand binding sites outside
Receptors
Questions to ask
1) Diversity in receptors. What could it mean ?
2) Using two subunits to make a receptor? Why? What advantage?
3) Signal integration at the tail ?
4) Signal integration at tail, what advantage or disadvantage does it bring?
May have subunits/ co receptors
Integrins: alpha/beta
beta is more prominent in the interior side
Short cytoplasmic tails may require co receptors
BCR: CD79 alpha/beta
TCR: hexameric CD3 complex
Photos
After receptor binding
Phosphorylation
Reciprocal phosphorylation
Clustering
Clustering
IgM and IgD
Then movement into lipid rafts
Dimerization
GF receptors
Stabilising molecules
BCR: CD19/21
TCR: CD4 and CD28 (With CD80/86)
Diversity
There exist multiple receptors for the same ligand
a combo may act together
Relative concentrations may differ
Relative affinities may differ
Is this compromised by the fact that there is only one downstream molecule
Cytoskeleton
Tubulin
Dynamic instability
