Biological Membranes

Team Teaching:
z Dr.rer.nat. Mo Awwanah, S.Si, M.Sc
Dr. Nadya Farah, S.Si, M.Si

Department of Military Biology

Faculty of Military Sciences and Technology
The Republic of Indonesia Defense University
 The Function
z of Biological Membranes
• Membranes define boundaries (of cells or organelles) and serve as
permeability barriers
• Membranes are site of specific proteins
with specific functions
• Membrane proteins regulate the transport
of solutes
• Membrane proteins (receptors) detect
and transmit electrical and chemical
signal
• Membrane proteins mediate cell-cell
adhesion and communication
Cell-cell contacts or adhesion is mediated
by proteins known as cadherins.
Cell-cell communication is facilitated by
proteins at the cell junctions in animals or
plasmodesmata in plants.
Campbell et al., 2018; Hardin et. al., 2012
Characteristics
z of Biological Membranes
• Selective permeable
Some substances can cross the membranes easier
than others.
• Components
The main components of membrane are lipids (the
majority: phospholipids) and proteins. Carbohydrates
sometimes associate with the proteins in membranes.
The phospholipids are arranged in two layers
(phospholipid bilayer).
• Amphipathic
Phospholipid has both a hydrophilic (“water-loving”)
region and a hydrophobic (“water-fearing”) region.
Membrane proteins are also amphipathic. They can
reside in the phospholipid bilayer with their hydrophilic
regions protruding.
Campbell et al., 2018
Biological
z Membranes are Fluid Mosaic
The structure of membrane as a mosaic of components —including
phospholipids, cholesterol, proteins, and carbohydrates—that gives the
membrane a fluid character.

Campbell et al., 2018

 The Composition
z
of Biological Membranes

Hardin et. al., 2012

 The Timeline
z
for the Development of the Fluid Mosaic Model
• Overton and Langmuir: Lipids are
important components of the membranes.
Overton
Lipids are present on the cell surface as
some sort of “coat”. Lipid-soluble
substances penetrate readily into cells,
whereas water-soluble substances do not.
Langmuir
Lipid monolayer. Phospholipids orient
themselves on water with their hydrophilic
heads face the water and their hydrophobic
tails protrude away from the water.
• Gorter and Grendel: the basic of
membrane structure is a lipid bilayer.
• Davson and Danielli: membranes also
contain proteins on both sides.
Hardin et. al., 2012
 The Timeline
z
for the Development of the Fluid Mosaic Model
• Robertson: all membranes share a
common underlying structure (trilaminar
pattern).

• Singer and Nicolson: a membrane

consists of a mosaic of proteins in a
fluid lipid bilayer (fluid mosaic model).
• Unwin and Henderson: most
membrane proteins contain
transmembrane segments
• (g-h)Development of membrane studies
Hardin et. al., 2012
The Fluid
z Mosaic Model of Membrane Structure
• Singer and Nicolson: a membrane consists of
a mosaic of proteins in a fluid lipid bilayer.

• Three classes of membrane proteins:

1. Integral membrane proteins
2. Peripheral proteins
3. Lipid-anchored proteins

• The transmembrane segment of an integral

membrane protein shows an α-helical
structure.
• Each α-helix typically consists of about 20–30
amino acids (represented by small circles).
• Many integral membrane proteins of the
plasma membrane have carbohydrate side
chains attached to the hydrophilic segments
on the outer membrane surface.
Hardin et. al., 2012
Lipid Microdomains
z or Lipid Rafts
• The proteins are not randomly distributed in the membrane. Groups of proteins
are often associated in long-lasting, specialized patches, where they carry out
common functions. Specific lipids are also found in these patches.
• Lipid microdomains (lipid rafts) are localized regions of membrane lipids with
some associated proteins that collectively perform certain function in cell
signaling.

Alberts et. al., 2015; Campbell et al., 2018

The Fluidity
z of Membranes
• The experiment by Larry and Michael Edidin by
mixing the mouse and human membrane proteins
indicates that some membrane proteins move
sideways within the plane of the plasma membrane.
• The fluidity of a membrane affects both its
permeability and the ability of membrane proteins to
move to where their function is needed.
• However, membranes that are too fluid cannot
support protein function either.
• Factors that affect membrane fluidity are fatty acid/
hydrocarbon tails and the presence of steroid
cholesterol.

Campbell et al., 2018

 Membrane
z Lipids: The ‘Fluid’ Parts of the Model

There are three major classes of membrane lipids:

• Phospholipids
- Phosphoglycerides (phosphatidylcholine,
phosphatidylethanolamine, phosphatidylserine, and
phosphatidylinositol)
- Sphingolipids (sphingomyelin in animal plasma
membrane, but absent in plant or most bacteria)
• Glycolipids
Glycolipids are formed by adding carbohydrate groups to
lipids. Ex. cerebrosides and gangliosides.
• Sterols: cholesterols and phytosterols (campesterol,
Hardin et. al., 2012 sitosterol, and stigmasterol)
Phospholipid
z
Composition od Several Kinds of Membranes

Hardin et. al., 2012

Analyzing
z Lipid Composition
• Thin-layer chromatography (TLC) is an important technique for lipid analysis
• TLC steps:
- A sample is spotted and dried onto a small area of a glass or metal plate coated
with a thin layer of silicic acid
- The TLC plate is then placed in a nonpolar organic solvent such as acetone and
chloroform
- Components of the sample are then carried upward by the solvent and separated
according to their polarity
- Less polar lipids such as cholesterol do not adhere strongly to the silicic acid and
move further up the plate, while more polar lipids remain closer to the origin.

The pattern shown is for lipids of the

erythrocyte plasma membrane.
The main components: cholesterol,
phosphatidylethanolamine (PE),
phosphatidylcholine (PC), and
phosphatidylserine (PS)
Hardin et. al., 2012
Lipids zare Mobile
• Membrane asymmetry: most lipids are distributed unequally between the two
monolayers.
• The unequal distribution of lipids between the two monolayers are resulted from the
movement of lipids.
• Three types of lipid movements within membrane:
- Transverse diffusion (‘flip-flop’)
- Rotation
- Lateral diffusion
• Fluorescence Recovery After Photobleaching (FRAP)
analysis to determine lipid mobility in membranes

Hardin et. al., 2012

Membrane
z Proteins: The ‘Mosaic’ Part of the Model
Singer and Nicolson: a membrane consists of a
mosaic of proteins in a fluid lipid bilayer.

Classification of membrane proteins:

• Integral membrane proteins
Integral membrane proteins are anchored to the
hydrophobic interior of the membrane by
hydrophobic transmembrane segments (light
purple), while hydrophilic segments (dark purple)
extend outward on one or both sides of the
membrane.
• Peripheral proteins
Peripheral membrane proteins are much more
hydrophilic and are therefore associated with the
membrane surface by weak electrostatic forces.
• Lipid-anchored proteins
Lipid-anchored proteins are essentially hydrophilic
proteins and therefore reside on membrane
surfaces, but they are covalently attached to lipid
molecules that are embedded within the bilayer. Hardin et. al., 2012
Integral
z Membrane Proteins

Types of integral proteins:

• Integral monotopic proteins
Integral monotopic proteins are embedded in and protrude from only one side of the bilayer.
• Transmembrane proteins
Transmembrane proteins span the membrane and have hydrophilic regions protruding from the
membrane on both sides.
- Singlepass proteins, the proteins cross the membrane once. Ex. Glycophorin.
- Multipass proteins, the proteins cross the membrane several times. Ex. Bacteriorhodopsin.
Some multipass proteins consist of a single polypeptide, whereas others have two or more
polypeptides (multisubunit proteins).
Hardin et. al., 2012
Peripheral
z Membrane Proteins

• Peripheral membrane proteins lack discrete hydrophobic sequences and

therefore do not penetrate into the lipid bilayer.
• Instead, they are bound to membrane surfaces through weak electrostatic
forces and hydrogen bonding with the hydrophilic portions of integral proteins
and perhaps with the polar head groups of membrane lipids.
• Ex. Peripheral proteins (spectrin, ankyrin, and a protein called band) of the
erythrocyte plasma membrane.
Hardin et. al., 2012
Lipid-anchored
z Membrane Proteins

GPI-anchored
protein
There are several mechanisms for attaching lipid-anchored proteins to membrane:
• Fatty acid-anchored membrane proteins
The protein is synthesized in the cytosol and then covalently attached to a saturated fatty acid
embedded within the membrane bilayer, usually myristic acid (14 carbons) or palmitic acid (16
carbons).
• Isoprenylated membrane proteins
The protein is synthesized as soluble cytosol proteins before being modified by addition of
multiple 5-carbon isoprenyl groups.
• GPI-anchored membrane proteins
The protein is made in the endoplasmic reticulum as a singlepass transmembrane protein that
subsequently have its transmembrane segment cleaved off and replaced by a GPI anchor.
Hardin et. al., 2012
Protein zIsolation by SDS-polyacrylamide Gel Electrophoresis
• Sodium dodecyl sulfate (SDS) allows isolation and fractionation of integral membrane
proteins

Isolation/ fractionation Separation of proteins by Visualization by

of membrane proteins SDS-polyacrylamide gel western-blotting
electrophoresis
• Determining the 3D structure by X-ray crystallography
Hardin et. al., 2012
Functions
z of Membrane Proteins

ACE2 is an
example of human
membrane protein
functions as a
receptor for SARS-
CoV2.

Campbell et. al., 2018. Gambar interaksi SARS-CoV2 dan ACE2 dari website Fakultas Farmasi UGM
Membrane
z Proteins are Mobile
Cell fusion experiments to determine the mobility of proteins

Hardin et. al., 2012

Glycosylation
z of Membrane Proteins
• Glycoproteins are membrane proteins with carbohydrate chains covalently
linked to amino acid side chains.
• The addition of a carbohydrate side chain to a protein is called glycosylation:
- N-linked glycosylation, linkage of the carbohydrate to the nitrogen atom of
an amino group.
- O-linked glycosylation, linkage of the carbohydrate to the oxygen atom of a
hydroxyl group.
• Most common carbohydrate found in glycoproteins:

Hardin et. al., 2012

The Role
z
of Membrane Carbohydrates in Cell-Cell Recognition
• Cell-cell recognition is a cell’s ability to distinguish one type of neighboring cell from
another. It is crucial to the functioning of an organism.
• Examples of the importance of cell-cell recognition:
- It is important, for example, in the sorting of cells into tissues and organs in an
animal embryo.
- It is also the basis for the rejection of foreign cells by the immune system, an
important line of defense in vertebrate animals.
- Cells recognize other cells by binding to molecules, often containing
carbohydrates, on the extracellular surface of the plasma membrane.
• Most membranes contain small but significant amount of carbohydrate. Except for
chloroplast, mitochondrial and bacterial membranes are not glycosylated.
• The carbohydrate can be associated with membrane lipids and form glycolipids, or it
can be also associated with membrane proteins and form glycoproteins.

Campbell et. al., 2018

Synthesiszof Membrane Components and Their Orientation in the Membrane

Campbell et. al., 2018

z

THANK YOU
z