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Lecture 18:
Introduction to Membranes
Lipid Structure
Properties of Lipid Bilayers
Biological Membranes Define the Boundaries
of the Cell and its Compartments
Lysozome
Mitochondria
Golgi complex
Endoplasmic
Reticulum
Nutrients
Wastes
Peroxisome
Nucleus
Plasma membrane
Membranes are permeability
barriers that keep the cell
contents in and unwanted
substances out.
Membranes are selectively
permeable: specific substances
can cross membranes in a
controlled way through
protein-based transport
systems.
The various organelles and
compartments of the cells are
bounded by membranes to
create interior environments
suitable for different functions.
Common Features of Biological Membranes
Membranes are sheet-like structures, 2 molecules thick, or 60 to 100
Angstroms across.
Lipids and proteins are the major components of membranes, occurring
in the ratio of 1:4 to 4:1. Both can be covalently modified by carbohydrates.
Lipids are small molecules with both hydrophobic and hydrophilic groups.
They associate to form double layers called lipid bilayers, which are
impermeable to polar molecules.
Proteins associated with or embedded in the lipid bilayer carry out the
different functions of membranes. These proteins serve as pumps, channels,
receptors, energy transducers, and enzymes.
Both lipid and protein components of membranes are held together
by noncovalent bonds.
Membranes are asymmetric- the two layers are not equivalent. Lipids can
flow and diffuse within a layer, but cannot in general cross to the other layer.
Most membranes are electrically polarized, enabling transport of molecules,
energy conversion, and transmission of signals.
Schematic Structure of a Membrane Lipid
Nonpolar
“tails”
Polar
“head”
Schematic Structure of a Lipid Bilayer
Layer 1
Layer 2
Example Functions of Membranes
PERMEABILITY BARRIERS:
Regulation of molecular and ionic compositions of cells
and intracellular organelles
a) channels & pumps (proteins that act as selective transport systems)
b) electrical polarization of membrane (due to differences in ion
concentrations on opposite sides)
INFORMATION PROCESSING
biological communication
a) signal reception by specific protein receptors (BINDING)
b) transmission/transduction of signals (via protein conformational changes)
ENERGY CONVERSION
ordered arrays of enzymes to organize of reaction sequences
a) photosynthesis (conversion of light energy to provide chemical bond
energy)
b) oxidative phosphorylation (oxidation of fuel molecules to provide
chemical bond energy)
Lipids
Lipids are a diverse group of biological molecules which share
the common solubility property of being insoluble in water but
highly soluble in organic solvents.
Lipids can serve diverse biological roles (energy sources,
signalling molecules) but we will focus on membrane lipidslipids whose primary role is as components of biological
membranes.
Three major types of membrane lipids:
Phospholipids
Glycolipids
Cholesterol
Fatty Acids
Fatty acids are components of phospholipids and glycolipids.
They consist of long hydrocarbon chains that terminate with
a carboxylic acid.
Palmitate:
16 carbons
(fully saturated)
The hydrocarbons of fatty acids vary in length (16 and 18 carbons
are the most common) and also in the number and position of double
bonds.
Kink at 9th carbon
Oleate:
18 carbons
(monounsaturated)
Description of Fatty Acids
An alkane is a hydrocarbon with no double bonds.
An alkene is a hydrocarbon containing one or more double bonds.
A shorthand notation to describe the degree of unsaturation:
18:0 represents a fatty acid with 18 carbons and 0 double bonds
18:1 represents a fatty acid with 18 carbons and 1 double bond
18:2 represents a fatty acid with 18 carbons and 2 double bonds…
Fatty Acid Nomenclature:
Substitute oic for e in name of parent alkane:
octadecane is an alkane with 18 carbons
octadecanoic acid is the fatty acid derived from octadecane (18:0)
Substitute enoic for ene in name of parent alkene:
octadecene is an alkene with 18 carbons, 1 double bond
octadecenoic acid is the fatty acid derived from octadecene (18:1)
Fatty acids containing more than one double bond are given the
suffixes -dienoic, -trienoic, etc.
octadecadienoic acid has 18 carbons and 2 double bonds (18:2)
octadecatrienoic acid has 18 carbons and 3 double bonds (18:3)
The carbon atoms are numbered from the carboxyl group.
The position of double bonds, and whether they are cis or trans, can
be indicated by the D notation, e.g. oleate can be referred to as
cis-D9-octadecenoate (cis double bond between carbons 9 and 10)
trans
cis
The last carbon is referred to as the w carbon.
Oleate
Consuming foods rich in w-3 fatty acids, such as salmon, is believed
to protect against heart disease.
Phospholipids and Glycolipids
Phospholipids are a major class of membrane lipids, and are comprised
of a “platform” or central backbone compound (glycerol or sphingosine),
fatty acids, a phosphate, and an alcohol. The presence of a phosphate
group is the primary identifier. These have charged head groups.
Glycerol:
CH
OH
2
CH
CH
OH
OH
Sphingosine:
2
Glycolipids are another class of membrane lipids. The platform is
sphingosine, with a fatty acid linked to the amino group and one or
more sugars to the primary hydroxyl. These have polar head groups.
Phosphoglycerides
Phosphate-containing lipids built from glycerol are phosphoglycerides.
They contain 2 fatty acids esterified to two of the hydroxyl groups on
glycerol, and the third hydroxyl is esterified to phosphoric acid. The
phosphate group is typically further esterified to other alcohols.
Alcohol
O
Phosphate
-
O
P
O
Glycerol
CH
CH
CH
O
O
H
C
O C
R1
Nonpolar fatty
acid tails
Polar (charged)
head group
2
O
R2
Fatty Acids
O
The simplest
phosphoglyceride is
phosphatidate in which
the phosphate is not
esterified.
Other common
phosphoglycerides
can be formed by
addition of hydroxylcontaining groups:
serine, choline,
ethanolamine, inositol.
(lecithin)
Sphingophospholipids
An example of phospholipids based on sphingosine are the
sphingomyelins. The amino group of sphingosine forms an
amide bond to a fatty acid and the primary hydroxyl is esterified
to phosphoryl choline or phosphoryl ethanolamine.
Nonpolar tails
Polar (charged)
head group
Glycolipids
Glycolipids are based on sphingosine and also form an amide bond
with a fatty acid. The primary hydroxyl is esterified to one or more sugars.
Cerebrosides have a single sugar and gangliosides have a branched chain
of up to seven sugars.
Glycolipids are found on the exterior layer of the plasma membrane with
the sugars ouside the cell.
Nonpolar tails
Polar head group
Phospholipids
(charged)
Phosphoglycerides
(based on glycerol)
Sphingophospholipids
(based on sphingosine)
Phosphatidyl choline
Phospatidyl serine
Sphingomyelins
Glycolipids
(based on sphingosine. uncharged)
Cerebrosides
Gangliosides
Nonpolar tails
Polar or charged
head group
Cholesterol
An important lipid of entirely different form is cholesterol. Its backbone is
a steroid, a 4-ring structure, with a hydrocarbon tail, and a polar hydroxyl
group. It is particularly abundant in some kinds of nerve cell membranes.
Lipids Spontaneously Form Bilayers
In aqueous solution, the nonpolar tails of phospholipids and glycolipids
tend to associate to minimize contact with water, but the polar head
groups tend to seek contact with water. Two ways to satisfy both
requirements are to form micelles or bilayers.
Micelles are formed by
fatty acids, detergents.
Typically smaller than
200 Angstroms.
Bilayers are formed by phospholipids.
The 2 fatty acid chains are too large to
fit in the interior of a micelle.
Bilayers can be very large, up
to 107 Angstroms (1 mm).
Bilayer Self-Assembly
Bilayers are stabilized primarily by hydrophobic interactions between the
nonpolar tails but also by Van der Waals interactions and also hydrogen
bonding between the polar head groups and water.
Bilayers seek to avoid exposure of the hydrophobic tails of lipids to water
so can be very extensive.
To avoid such exposure they form closed compartments.
Any holes that form in the bilayer are energetically unfavorable so
bilayers are self-sealing.
Formation of Lipid Vesicles
The self-sealing property of bilayers allows creation of lipid vesicles
or liposomes- small membrane-bounded compartments containing
a desired substance.
These vesicles have clinical uses such as drug delivery.
The ability to create membranes with concentration gradients across them
is useful for the study of membrane proteins.
Permeability of Bilayers
Bilayers are nearly impermeable to ions
and most polar molecules other than
water.
The rate at which such substances
traverse the membrane is correlated with
their solubility in nonpolar solvents.
Polar or charged molecules must be
desolvated (shed bound water) before
they can spontaneously cross the
membrane, which is unfavorable.
Summary:
Biological membranes are composed of lipids and proteins and form the
boundary of the cell and its compartments.
Phospholipids and glycolipids are formed of fatty acids esterified
to a platform molecule and contain other groups such as alcohols
or sugars.
Lipids spontaneously assemble into bilayers which are largely
impermeable to charged and polar molecules and which form
closed compartments.
Key Concepts:
Fatty acids
Phospholipids
Glycolipids
Cholesterol
Micelles
Bilayers
Vesicles
Permeability of bilayers