Conclucion

What we have learnt so far !

Phase behavior of phospholipids and
other surfactants:
Morphology of lipid assemblies
Phospholipids and detergents
both have head groups and the
tail parts on the molecule
Actual viewing:
• Surfactants and phospholipids molecules
preferentially adsorb at an interface, alter
interfacial free energy (work needed to create
or expand interface/unit area).

• Surface free energy of interface can minimized

by reducing interfacial area.
 SURFACTANT CLASSES
Anionic (~ 60% of industrial surfactants)
Cationic (~ 10% of industrial surfactants)

Non-ionic (~ 25% of industrial surfactants)

The most outstanding futures of these
molecules are:
1- Their molecular areas are around 30-50 °A2,

2- The polar head group is virtually parallel to the plane bilayer; the amino
group is hydrogen bonded to unesterified phosphate oxygens of an adjacent
molecule; The glyceroo group is essentially oriented normal to the plane of
the bilayer,

3- The sn2 fatty acid chain extends parallel to the plane of the bilayer for first
two carbons and then is directed down into the bilayer. The sn1 fatty acid
extends directly into the bilayer,

4- The acyl chain are directed perpendicular to the bilayer surface and, with
the exeption of the initial part of the sn-2 fatty acid, are in fully extended, all-
trans configuration.
Detailed structure of phosphotidyl
cholin molecule
 A: PEA in crystall form, acyl groups the
same,
 B: PEA in liquid crystall form, ater or
other polar solvent bridges the gap
between neighbors and stabilizes the
structures,
 C: PC in theoretical arrangement and
showing that the space between head
groups are (50 A°) which larger than
required space (Actual value is 38 A°),
 D: PC Arrangement in overlapping
fashion,
 E: Lamellar gel phase arrangement,
accomodating larger cross sectional
area (50 A°2) ,
 F: Arrangement in lamellar luquid
crystalline phase, PC does not require
the head group lattice to be distrupted.
 Major futures of crystall structures
considering improtance for lipid bilayers:
1-Structures all in lamellar, polar and non polar groups organized as
in bilayers,
2- PC and cerebrosides have packaging problem because of bulky
head groups, this is important for the properties of biological and
model membranes,
3-The polar headgroups essentially lie flat in the plane of the
bilayer, with intermolecular hydrogen bonding,
4- Acyl chains (saturated) are in all-trans configuration,
5- The sn-2 fatty acyl chain does not extend into the bilayer until
after C2 position.
Lipid-water mixtures:

Lamellar gel phase Lamellar luqiud

crystalline phase

Hexagonal I phase
Hexagonal II phase
 Lipid hydration:

Many lipids are swell in water.

Lipids which are neutral or isoelectric (PC) show no or limitted
swelling (limitted water layers between lamellae).

In excess water two phase exist. Charged lipids show continious

swelling with water up to certain threshold.

The stability of multilamellar or unilamellar structures are

determined by electrostatic interactions.

Polarisation of water molecules by lipid polar head groups results

In strong repulsive effect for bilayers.
 Micelles
• If concentration is sufficiently high, surfactants can form
aggregates in aqueous solution ⇒ micelles.
• Typically spheroidal particles of 2.5-6 nm diameter.
 CMC Values
- General Trends -
(1) For the same head group, CMC decreases with increasing
alkyl chain length
(2) CMC of neutral surfactants lower than ionic
(3) CMC of ionic surfactants decreases with increasing salt
concentration.
(4) For the same head group and alkyl chain length, CMC
increases with increase in number of ethylene oxide (EO)
groups.
(5) For mixed anionic-cationic surfactants, CMC much lower
compared to those of pure components.
Shapes:
1-Spherical: Highest area/volume ratio
2-Distorted spheres: lower area/volume ratio
a-Elipsoids: packing would be highly
infavorable (such as at the edge)
b-Globular, bilobed: Two joined spheres
A likely form.
3-Rods and cylinder Even lower area/volume
ratio
4-Bilayer: The smalest area/volume ratio
 Head group orientation in the
bilayer
It has been investigating by several techniques and almost all
of them indicate that lipid polar head groups are oriented
approximately parallel to the plane of the bilayer. It was shwon
for PC,PS etc. for both gel and crystalline phases.

In contrast, PG(Phosphatidiylglycerol) from E.coli head group

oriented 30º from the membrane surface. The head group
hydrogen bonding is found to be important.
Lipid Phase Molecular Critical
shape packing
parameter

Detergents <1/3 sphere

Lysophospholipids
1/3 to 1/2
Globular to rids
Inverted cone
PC 1/2 to 1
Sphongomyelin
PS,Pino,Pgly.Pacid
Cadiolipin
Cylindrical
PEA >1
CaridolipinCa++
PACa++ pH<6
PA pH<3
Cone
PS pH<4
Modified liposomes
(stealth liposomes)

hydrophilic polyoxyethylene lipids

incorporated into liposome

Increased half-life is be due to

a reduced coating (opsonisation)
of these liposomes by plasma proteins

cholesterol,
polyvinyl-pyrrolidone polyacrylamide lipids,
glucoronic acid lipids are working the same….

So liver cells not able to uptake them

 Cochleates – multilayer lipid rolls

1. Storageable without any problems – could be lyophilized

(at least one year as a lyophilized powder at room temperature)!

2. Durable – survive multiple membrane fusion event

(fuse-release drug-disengage-fuse-release..)
3. Can survive in GI tract
Cochleates have been shown to be an effective oral delivery system.
We have seen some examples
from the literature data bases:
how to use some techniques and
how to make a conclusion and
interpretations.
 Techniques to study amphiphilic
molecules behavior and
orientations and some possible
interactions

X-ray crystallography, NMR, Freeze-fructure/etch EM,

Raman spectroscopy, IR, Neutron diffraction, monolayers,
Major thermodinamic driving force to
stabilize hydrated lipid is hydrophobic force
(hydrophobicicty determines this,
thermodynamic force for packing the
molecules in water)

van der Waals (weak, short attractive force

because of polarized electrons on the
carbon chains)

Hydrogen bonding between polar head

groups (inter molcular bridging)
We have seen some examples
from the literature (recent ones)
data bases related to monolayers
and applications of the technique
has been shown and conclusion
and interpretations were reviewed.