Week 5: Concepts of self assembly Flashcards
What is the formula for the partial molar Gibbs free energy of a biomolecular system?
(35)
What is the total Gibbs free energy?
The sum of the partial free energies of its components.
(36)
What are the common themes of aggregating self-assembly in molecular biophysics?
1) A critical micelle concentration exists - A value of the concentration of sub-units above which self-assembly occurs.
2) Entropy change is positive on assembly as the aggregate becomes more ordered.
3) Hydrogen bonding and hydrophobicity are often an important driving factor.
4) Surface free energy is minimised as the self-assembly proceeds.
How does self-assembly depend on the dimensionality of the system?
Self-assembly in 1D produces a number of highly polydisperse aggregates.
2D tends to form a single raft or small sheet.
3D tends to form a single micelle, aggregate or crystal.
What drives self-assembly?
The minimisation of surface free energy.
How is a sickle cell an example of self-assembly?
Sickle shaped cells are formed from fibrous aggregates of misfolded haemoglobin molecules causing elongated structures on the membrane surface.
How are giant self-assembled beta sheets an example of self-assembly?
They are thought to be responsible for a range of prion diseases.
A hierarchy of structures is found with model peptide systems as a function of peptide concentration.
The diameters of the resultant fibres are controlled by the chirality of the peptide monomers.
An example of self-assembly is the cell membrane. Sketch a diagram of this.
(37)
Phospholipids
Ligands
Proteins
Cholesterol
Ion channel
What is the typical range of critical micelle concentrations (CMCs) for a single chained phospholipid?
10^-2 to 10^-5 M
What is the typical range of critical micelle concentrations (CMCs) for a double chained phospholipid?
10^-2 to 10^-9 M
Sketch the graph of monomers and aggregate concentrations as a function of the total concentration of lipids.
(38)
What happens at an oil-water interface stabilised by a small amount of surfactant?
Some surfactant molecules are dissolved in the bulk oil or water regions, but most migrate to the boundary of the interface.
What does the requirement that the chemical potential of all identical molecules in the different sized aggregates are equal result in?
(39)
What is the chemical potential of an N-mer aggregate?
(40)
What is the definition if the dissociation constant?
(41)
How can the concentrations of A and B be used to find the dissociation constant?
(42)
How would you find the critical micelle concentration for the process of self-assembly?
(43)
What is the general formula for the CMC of surfactant aggregates and 3D aggregates?
(44)
What are general features of surfactants?
Surface active agent
A hydrophobic tail and a hydrophilic head.
Amphiphilic or an amphiphile, mimicking the basic feature of nature lipids.
From the head group:
Cationic
Anionic
Nonionic
Zwitterionic
Often water soluble.
Adsorption at interfaces.
Aggregation in the bulk above CMC.
What is the Gibbs equation?
(45)
What is formula for area per molecule adsorbed?
(46)
CMC measurements.
Relying on how the concentrations of surfactant as monomer and then aggregates affect the physical property that is measured.
Above CMC, the property measured do not change much with further increasing surfactant concentration due to the micellesation.
Most common approaches are to measure surface tension changes.
Also changes in properties across the CMC. (dye environment or conductance/conductivity)
What is the formula for critical packing parameter?
CPP = V/(AL)
V = volume
A = head area
L = tail length
What do the different CPP values mean?
If CPP ~ 1, lamellar layer of La (L alpha) phase.
If CPP < 1/3, o/w micelles - likely to be spherical.
If 1/3 < CPP < 1/2, hexagonal packing.
If CPP > 1, V is large, possible w/o micelles.
Why is the reality for aggregate size shape and transitions?
Reality is complex as T, ion binding, ionic strength, head or tail conformation and solvent polarity affect real size, shape and transitions.
Sketch a parallel beta sheet.
(47)
Sketch an antiparallel beta sheet.
(48)
Where is aggregating protein self assembly important?
In amyloid diseases (Alzheimer’s, BSE etc) and the aggregation of haemoglobin molecules in sickle cell anaemia.
What happens in the self assembly of proteins at high temperatures?
The reaction proceeds more favourably at high temperatures.
The reverse is true for standard polymerisation reactions.
The entropy change is positive for the self assembly process.
(49)
Sketch the process of collagen fibres form from protofilaments.
(50)
Sketch the process of lamin fibres form from protofilaments.
(51)
Sketch the process of vimentin fibres form from protofilaments.
(52)
General points about phospholipids and membrane bilayer:
Phospholipid structure - comprised of dichain hydrophobic tails and a hydrophilic head (charged, neutral or zwitterionic).
Amphiphilic - can form a monolayer or bilayer.
Hardly soluble in water but surface spreadable.
General points about surfactant structure and properties:
Structure - comprised of a hydrophobic tail and a hydrophilic head.
Amphiphilic - can adsorb at interfaces.
Good solubility in water but limited solubility in oil.
Smaller size than natural membrane lipids.
Interfacial adsorption, concept of Gibbs equation and aggregation CMC.
Things to know for peptides and proteins:
Amino acids make peptides that make proteins.
Amphiphilic and charged. Prone to folding and refolding, depending on environments.
Helix and sheet models.
Describe the main structural features of a surfactant and outline its key physical properties.
Hydrophobic dodecyl chain and hydrophilic charged head.
Being amphilic, the molecules would be soluble in water but prefer to adsorb at interfaces with their dodecyl chains staying out of water.
As more surfactant is dissolved their surface and bulk concentration will go up but by a certain point, further addition of SDS will contribute to the formation of micellar aggregates (CMC).
Above the CMC, the monomer concentration and surface concentration remain constant.
Describe what the critical micellar concentration means.
Explain why the concentrations of monomer and micelle change in a typical surfactant solution the way they do.
CMC is the point above which further addition of surfactant leads to the formation of micellar aggregates.
As monomer concentration increases, the surface concentration adsorbed amount also increases until the CMC, above which both the bulk monomer and surface concentrations cease to increase.
From the Gibbs equation, the surface tension will decrease with increasing bulk monomer concentration or with increasing surface concentration, till CMC.
Describe the main structural features of a phospholipid and outline its key physical properties.
Phospholipids contain two long chains (strongly hydrophobic) and a relatively small hydrophilic head (zwitterionic or charged).
They are hardly soluble but spreadable.
They can form lipid monolayers, bilayers or multilayers, as basic building blocks of membranes and barriers surrounding cells or subcellular compartments.
Other molecules such as membrane proteins can help further elaborate membrane structures to control diffusion and transport.
Briefly explain why a globular protein tends to unfold.
Natural globular proteins are made and fold into unique 3D structures in living environments where proteins are highly concentrated and surrounded by many other types of biomolecules such as peptides, lipids and nucleic acids.
When produced as aqueous solutions, the living environments are completely different, i.e. the scaffolding conditions, structurally and physiologically, are missing.
Given each protein has very different domain sizes, structure, charges and stability, they tend to unfold easily into clusters or aggregates to minimise the systems energy.
As a result, local structures inside these proteins can be damaged, compromising their biological functions.
What is a surfactant?
A chemical compound that decreases the surface tension or interfacial tension between two liquids, a liquid and a gas, or a liquid and a solid.
What is a micelle?
An aggregate or surfactant amphipathic lipid molecule dispersed in a liquid, forming a colloidal suspension.
A typical micelle in water forms an aggregate with the hydrophilic head regions in contact with surrounding solvent, sequestering the hydrophobic single-tail regions in the micelle centre.
What is an aggregate?
A term used to describe a collection of units or particles forming a body or mass.
