Cells and membranes

Plasma membrane

• surrounds all cells that acts as a selective barrier, detects chemical signals, anchors cells to adjacent cells and the extracellular matrix

Fluid-mosaic model

Integral membrane proteins are able to move freely laterally in lipid bilayer - amphipathic molecules align with lipid bilayer

4 types of membrane juctions

• integrins

• desmosomes

• tight junctions

• gap junctions

What are integrins

Binds to specific extracellular proteins and links adjacent proteins to other cells

What are desmosomes?

Dense plaques on plasma membrane that anchor cadherins - allow elasticity e.g. skin

What are gap junctions?

Protein-lined channels that link two cells - small diameter links what can be exchanged e.g. small molecules and ions only

What are tight junctions?

Extracellular surfaces of adjacent plasma membranes join together - occurs in band around circumference of the cell.

This allows control in types and amount of substances absorbed as cannot pass between cells.

Osmolarity

Total solute concentration in a solution: 1 osmol = 1 mol of solute particles

What is tonicity?

Measure of ability of a solution to add or remove water from cells due to osmosis

Isotonic

No change in cell volume

Hypotonic

Lower conc. of non-penetrating solutes outside cell (high conc. ofsoluted inside) so cell will swell 

Hypertonic

Higher conc. of non-penetrating solutes outside cell so cell will shrink

The possible results of a change in conformational shape of a receptor following binding of a chemical messenger are what?

1) Change in permeability/transport properties

2)Metabolism

3)Secretory activity 

4) Rate of proliferation/differenciation

5)Concentration of chemicals 

Properties of lipid soluble messengers

1) Can diffuse through plasma membrane

2) Have intracellular receptors

3) Receptors bind directly to recognised sequence and alter gene transcription

4) Slower response compared to membrane receptors but more sustained 

Properties of water soluble messengers

1) Broad range of receptors

2) Intracellular signalling cascades

3) Can activate downstream mediators

4) Faster response but less sustained e.g. adrenaline

4 types of water soluble messengers

A: Ligand-gated ion channels (conformational change when ligand binds leading to change in membrane potential)

B: Enzymatic activity (most are protein kinases) e.g. bound messenger changes conformation → receptor auto-phosphorylates tyrosine → these become docking sites for cytoplasmic proteins → docking proteins bind and activate signalling pathways

C: Interact with cytoplasmic Janus Kinases (JAKs) (no intrinsic kinase so must use JAKs

E: G-Protein-Coupled (bound to inactive receptor protein complex, made of 3 subunits which are alpha, beta, gamma). Works by ligand binding and conformation change → activated receptor inc. aff. of alpha subunit → when bound to GTP the alpha subunit dissociates and links with another plasma membrane protein

What kind of protein does Ca2+ bind to?

Cytosolic proteins, importantly calmodulin which changes shape and allows active calcium-calmodulin to control kinase activity so control other protein activity using ATP to phosphorylate them

Why is cessation of signalling important?

Chronic overstimulation of a cell can be detrimental e.g. cancer

Eicosanoid

Intracellular messengers released locally in paracrine or autocrine manner

Agonists

Chemical messengers that stimulate a normal cellular response

Antagonists

Substances that compete with the natural ligand for that receptor

What are the 4 major features that define interactions between receptors and their ligands?

1) Specificity - receptors ability to bind only one type of chemical messengers

2) Affinity - strength with which a chemical messenger binds (strong requires lower conc)

3) Saturation - as conc of messenger inc. the response inc. as more receptors are saturated, upper limit will eventually be reached

4) Competition - ability of a natural molecule to compete with a natural ligand to bind to receptor

What determines specificity of cell membranes?

1) Pore size

2) Charge

3) Binding site

What is flux?

The amount of material crossing a surface in a unit of time

Diagram of movement of all substances

What are the three major types of protein channels that span cell membranes?

• ligand gated

• voltage gated

• mechanically gated

What is the molarity of pure water?

55.5M

What is osmolarity?

The total solute concentration of a solution (extracellular fluid normally 285-300 mOsm

Hwat is osmotic pressure?

The ‘force’ required to prevent the flow of water into a solution

What is a semipermeable membrane?

A membrane permeable to water but not solutes

What are nonpenetrating solutes and give examples

Substances that cannot cross the plasma membrane e.g. Na+ and Cl- ions on the outside of the cell membrane or K+ on the inside of the membrane

What are 3 types of endocytosis?

• pintocytosis: vesicle contains extracellular fluid with non-specific components water, ions, nutrients ect

• phagocytosis: engulfing bacteria/cell debris

• receptor mediated endocytosis: pathway for larger moleucles (e.g. proteins) which works when receptors bind to ligands, recruiting clathrin to form a pit and then vesicle

Describe epithelial transport

• occurs in paracellular pathway through tight junctions

What effect do ligands have when bound to proteins?

Changes conformation causing function to be activated or inactivated

What two factors are needed for chemical specificity?

• close proximity

• complementary conformational shape

What is needed for high affinity binding site?

Correct shape and electrical charges

WHat are two ways to control protein activity?

1) Alter protein shape → allosteric (regulatory site binding changes functional site (active)) or covalent modulation (bonding of charged chemical groups to side chains)

2) Regulate synthesis and degradation → more or less

What is cooperativity?

Ligand binds to first of several function sites increasing affinity of other functional areas

Give an example of covalent modulation and explain how it works

Phosphorylation → kinase adds phosphate group, phosphatase removes phosphate group (not in exam)

Swell (hypo: [soln]<[cell])

The concentration of water outside the cell is initially lower than the concentration inside the cell(Hyper: [soln]>[cell])