Week 5: Concepts of self assembly

Question 1

What is the formula for the partial molar Gibbs free energy of a biomolecular system?

Answer 1

(35)

Question 2

What is the total Gibbs free energy?

Answer 2

The sum of the partial free energies of its components.

(36)

Question 3

What are the common themes of aggregating self-assembly in molecular biophysics?

Answer 3

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.

Question 4

How does self-assembly depend on the dimensionality of the system?

Answer 4

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.

Question 5

What drives self-assembly?

Answer 5

The minimisation of surface free energy.

Question 6

How is a sickle cell an example of self-assembly?

Answer 6

Sickle shaped cells are formed from fibrous aggregates of misfolded haemoglobin molecules causing elongated structures on the membrane surface.

The haemoglobin is hydrophobic which causes this.

Question 7

How are giant self-assembled beta sheets an example of self-assembly?

Answer 7

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.

Question 8

An example of self-assembly is the cell membrane. Sketch a diagram of this.

Answer 8

(37)

Phospholipids
Ligands
Proteins
Cholesterol
Ion channel

Question 9

What is the typical range of critical micelle concentrations (CMCs) for a single chained phospholipid?

Answer 9

10^-2 to 10^-5 M

Question 10

What is the typical range of critical micelle concentrations (CMCs) for a double chained phospholipid?

Answer 10

10^-2 to 10^-9 M

Question 11

Sketch the graph of monomers and aggregate concentrations as a function of the total concentration of lipids.

Answer 11

(38)

Question 12

What happens at an oil-water interface stabilised by a small amount of surfactant?

Answer 12

Some surfactant molecules are dissolved in the bulk oil or water regions, but most migrate to the boundary of the interface.

Question 13

What does the requirement that the chemical potential of all identical molecules in the different sized aggregates are equal result in?

Answer 13

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Question 14

What is the chemical potential of an N-mer aggregate?

Answer 14

(40)

Question 15

What is the definition if the dissociation constant?

Answer 15

(41)

Question 16

How can the concentrations of A and B be used to find the dissociation constant?

Answer 16

(42)

Question 17

How would you find the critical micelle concentration for the process of self-assembly?

Answer 17

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Question 18

What is the general formula for the CMC of surfactant aggregates and 3D aggregates?

Answer 18

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Question 19

What are general features of surfactants?

Answer 19

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.

Question 20

What is the Gibbs equation?

Answer 20

(45)

Question 21

What is formula for area per molecule adsorbed?

Answer 21

(46)

Question 22

CMC measurements.

Answer 22

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)

Question 23

What is the formula for critical packing parameter?

Answer 23

CPP = V/(AL)

V = volume
A = head area
L = tail length

Question 24

What do the different CPP values mean?

Answer 24

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.

Question 25

Why is the reality for aggregate size shape and transitions?

Answer 25

Reality is complex as T, ion binding, ionic strength, head or tail conformation and solvent polarity affect real size, shape and transitions.

Question 26

Sketch a parallel beta sheet.

Answer 26

(47)

Question 27

Sketch an antiparallel beta sheet.

Answer 27

(48)

Question 28

Where is aggregating protein self assembly important?

Answer 28

In amyloid diseases (Alzheimer's, BSE etc) and the aggregation of haemoglobin molecules in sickle cell anaemia.

Question 29

What happens in the self assembly of proteins at high temperatures?

Answer 29

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)

Question 30

Sketch the process of collagen fibres form from protofilaments.

Answer 30

(50)

Question 31

Sketch the process of lamin fibres form from protofilaments.

Answer 31

(51)

Question 32

Sketch the process of vimentin fibres form from protofilaments.

Answer 32

(52)

Question 33

General points about phospholipids and membrane bilayer:

Answer 33

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.

Question 34

General points about surfactant structure and properties:

Answer 34

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.

Question 35

Things to know for peptides and proteins:

Answer 35

Amino acids make peptides that make proteins. Amphiphilic and charged. Prone to folding and refolding, depending on environments. Helix and sheet models.

Question 36

Describe the main structural features of a surfactant and outline its key physical properties.

Answer 36

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.

Question 37

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.

Answer 37

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.

Question 38

Describe the main structural features of a phospholipid and outline its key physical properties.

Answer 38

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.

Question 39

Briefly explain why a globular protein tends to unfold.

Answer 39

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.

Question 40

What is a surfactant?

Answer 40

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.

Question 41

What is a micelle?

Answer 41

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.

Question 42

What is an aggregate?

Answer 42

A term used to describe a collection of units or particles forming a body or mass.