BIO201
Introduction to
Biochemistry & Biotechnology
Lecture #11
Lehninger
Principles of Biochemistry
Chapter 11
Biological Membranes
Biological Membranes
Membranes: Common features
Biological membranes define cellular boundaries, divide cells into discrete compartments,
organize complex reaction sequences, and act in signal reception and energy
transformations.
Basic function of a cell membrane: to protect the cell from its surroundings.
Key features of biological membranes:
1. The biological membrane is made up of lipids with hydrophobic tails and hydrophilic
heads.
2. Phospholipids are abundant in all biological membranes.
3. The structure is highly fluid and most of the lipid and protein molecules can move about
in the plane of the membrane. The lipid and protein molecules are held together mainly
by non- covalent interactions. Sugars are attached by covalent bonds to some of the lipid
and protein molecules.
4. The cell membrane is selectively permeable to ions and organic molecules and controls
the movement of substances in and out of cells.
5. Integral membrane proteins float in this sea of lipid, held by hydrophobic interactions
with their nonpolar amino acid side chains.
6. Both proteins and lipids are free to move laterally in the plane of the bilayer, but
movement of either from one face of the bilayer to the other is restricted.
Q1. What is a membrane?
Q2. What is the basic function of a membrane?
Q3. Write six common features of biological membranes.
Biological Membranes
Membranes: Common features
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No question in exam from this slide.
Biological Membranes
Composition and Architecture
Composition: Membranes are composed of lipids and proteins in varying combinations
particular to each species, cell type, and organelle.
FIGURE 11–2 Lipid composition of the plasma
membrane and organelle membranes of a rat
hepatocyte.
✓ Lipid anchored
Q1. List the major molecules with which biological membranes are
composed of.
https://www.slideshare.net/AmitKumar2325/cell-membrane-and-transport-52246921
No question on Figure 11-2 in exam.
Biological Membranes
Composition and Architecture: Fluid Mosaic Model
The Singer-Nicholson fluid mosaic model of the plasma membrane describes the plasma membrane as
a fluid combination of phospholipids, cholesterol, and proteins. Carbohydrates attached to lipids
(glycolipids) and to proteins (glycoproteins) extend from the outward-facing surface of the membrane.
http://keywordsuggest.org/gallery/532229.html
Q1. What is Singer-Nicholson fluid mosaic model of cell membrane?
Q2. Draw a cell membrane according to the fluid mosaic model.
Q3. Write 5 features of cell membrane according to fluid mosaic model.
Biological Membranes
Composition and Architecture: Integral & Peripheral proteins
Membrane proteins: Membrane proteins can be divided operationally into two groups: integral and
peripheral. Peripheral proteins in membranes: Peripheral
Integral proteins in membranes: Integral membrane proteins are membrane
proteins are embedded within the lipid bilayer. They proteins that adhere only temporarily to the
cannot easily be removed from the cell biological membrane with which they are
membrane without the use of harsh detergents that associated. These proteins attach to
destroy the lipid bilayer. Example: Glycophorin, integral membrane proteins, or penetrate
Bacteriorhodopsin. the peripheral regions of the lipid bilayer.
Example: Ankyrin, Spectrin.
https://www.slideshare.net/mrtangextrahelp/tang-05-membrane-structure-and-functions
Q1. What are the two types of membrane proteins? Give examples.
Q2. Draw diagram to show the locations of peripheral and membrane proteins.
Q3. How can you isolate (i) integral proteins, (ii) ?
Biological Membranes
Composition and Architecture: Examples of Lipid-linked proteins
Lipid-linked membrane proteins: Lipid-anchored proteins (also known as lipid-linked proteins)
are proteins located on the surface of the cell membrane that are covalently attached to lipids
embedded within the cell membrane. These lipids insert and assume a place in the bilayer structure of
the membrane alongside the similar fatty acid tails.
Q1. What are lipid-linked membrane proteins?
Q2. Draw diagrams to describe five examples of lipid-linked membrane
proteins.
Biological Membranes
Membrane Dynamics: Why phospholipids spontaneously form bilayers in lab conditions?
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Being cylindrical, phospholipid molecules spontaneously form
bilayers in aqueous environments. In this energetically most-
favorable arrangement, the hydrophilic heads face the water at
each surface of the bilayer, and the hydrophobic tails are
shielded from the water in the interior.
Q1. Explain why phospholipids form bilayers in membranes.
Biological Membranes
Membrane Dynamics: Order of Acyl Groups in Bilayer interior
Throughout the biological world, a 30 Å
hydrophobic film typically delimits the
environments that serve as the margin between life
and death for individual cells. Nature Reviews Molecular Cell Biology 9, 112-124 (February 2008)
One remarkable feature of all biological membranes is their
flexibility—their ability to change shape without losing their integrity
and becoming leaky. The basis for this property is the noncovalent
interactions among lipids in the bilayer and the motions allowed to
individual lipids because they are not covalently anchored to one
another.
Q1. Mention a remarkable feature of cell membranes.
Q2. Explain why biological membranes are flexible.
Biological Membranes
Membrane Dynamics: Order of Acyl Groups in Bilayer interior
Although the lipid bilayer structure is quite stable, its individual phospholipid and
sterol molecules have some freedom of motion (Fig. 11–15). The structure and
flexibility of the lipid bilayer depend on temperature and on the kinds of lipids
present.
Lipid bilayer
Low High Moderate
temperature temperature temperature
Paracrystalline state Liquid-disordered state Liquid-ordered state
(gel-phase) (fluid state) (physiological state)
All types of motion of The interior of the bilayer is Less motion of acyl chains
individual lipid molecules in more fluid than solid and than the fluid state but
the bilayer are strongly the bilayer is like a sea of lateral movement in the
constrained, and the constantly moving lipids. plane of the bilayer still
interior of the bilayer is Acyl chains undergo much takes place. Individual
more solid than liquid. thermal motion and have no phospholipid molecules can
Polar head groups are regular organization. diffuse laterally but
uniformly arrayed at the the acyl groups remain
surface, and the acyl chains extended and more or less
are nearly motionless and ordered.
packed with
regular geometry.
http://onlinelibrary.wiley.com/doi/10.1016/0307-4412(91)90103-F/pdf
These differences in bilayer state are easily observed in liposomes
Q1. Discuss different types of lipid composed of a single lipid, but biological membranes contain many
bilayers of a liposome with a single
lipid. lipids with a variety of fatty acyl chains and thus do not show sharp
No question on the image of this phase changes with temperature.
slide in exams.
Biological Membranes
Membrane Dynamics: Factors affecting membrane fluidity
Cells regulate their lipid composition to achieve a Diagram showing the effect of
constant membrane fluidity under various growth unsaturated lipids on a bilayer.
The lipids with an unsaturated
conditions. For example, bacteria synthesize more
tail (blue) disrupt the packing
unsaturated fatty acids and fewer saturated ones when of those with only saturated
cultured at low temperatures than when cultured at tails (black). The resulting
higher temperatures. At lower temperatures, tails of bilayer (bottom) has more
saturated fatty acids might crystallize and hence fluidity at lower temperatures
behave like a solid (rigid structure). than the one with saturated
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lipids only (top).
Major factors that can affect membrane fluidity:
1. Lipid chains (acyl tails) with carbon-carbon double
bonds (unsaturated) are more fluid in membranes
than lipids that are saturated with hydrogens and
thus have only single bonds.
2. Shorter fatty acyl tails are less likely to interact,
which makes the membrane more fluid than
membranes with long acyl tails.
3. The rigid planar structure of the steroid nucleus in
sterols like cholesterol, inserted between fatty acyl
side chains, reduces the freedom of neighboring
fatty acyl chains to move by rotation about their
carbon–carbon bonds, forcing acyl chains into https://www.slideshare.net/robswatski/biol-101-chp-7-membrane-structure-and-function
their fully extended conformation. The presence of Q1. Give an example of maintaining the degree of fluidity in
sterols therefore doesn`t reduces the fluidity in the biological membranes.
core of the bilayer rather increase the fluidity, thus Q2. Discuss the major factors that can affect membrane fluidity.
favoring the liquid-ordered phase. Q3. Diagrammatically show the role of cholesterol in eukaryotic cell
membranes.
Biological Membranes
Membrane Dynamics: Transbilayer movement of lipids by enzymes
Transbilayer movement (flip-flop) of lipids in membrane:
At physiological temperature, transbilayer—or
“flipflop”—diffusion of a lipid molecule from one leaflet
of the bilayer to the other (Fig. 11–16a) occurs very
slowly if at all in most membranes.
Transbilayer movement requires that a polar or charged
head group leave its aqueous environment and move into
the hydrophobic interior of the bilayer, a process with a
large, positive free-energy change. There are, however,
situations in which such movement is essential. For
example, during synthesis of the bacterial plasma
membrane, phospholipids are produced on the inside
surface of the membrane and must undergo flip-flop
diffusion to enter the outer leaflet of the bilayer. Similar
transbilayer diffusion must also take place in eukaryotic
cells as membrane lipids synthesized in one organelle move
from the inner to the outer leaflet and into other
organelles. Q1. What is transbilayer movement? Why is it important?
Q2. Which enzymes carry out transbilayer movement?
Diagrammatically show lateral and transverse diffusions.
Q3. Give examples to explain the importance of transbilayer
movements in prokaryotic and eukaryotic cells.
Biological Membranes
Membrane Dynamics: Transbilayer movement of lipids by enzymes
Different classes of lipid transporters:
Lipid transporters transport or flip lipids across the bilayers. There exist three major classes of
Lipid Transporters:
ATPases are a family of cation transporters that use energy from ATP hydrolysis to translocate ions/ metal cations across
1. P-type Flippase- (P-type
lipid bilayers)
2. ABC Flippase- (unique type of ATPase, acts as a machine to fuel the movement across membranes of almost any type of molecule, from large
polypeptides to small ions, via many different membrane-spanning proteins.)
3. Scramblases
P-type Flippase and ABC Flippase are energy-dependent (ATP) enzyme that can create lipid
asymmetry and transport specific lipids. Flippases mostly belong to P-type Flippase (e.g,
transport substrates of the rotary motor and also include the ion transporting Na+/K+-ATPase and
the Ca2+-ATPase) and it moves lipids from the exoplasmic to the cytosolic face.
A family of proteins, the flippases (Fig. 11–16b), facilitates flipflop diffusion, providing a
transmembrane path that is energetically more favorable and much faster than the uncatalyzed
movement.
Scramblases are energy-independent enzyme that
can dissipate lipid asymmetry and have a broad
lipid specificity.
They catalyze the bi-directional transport of lipids.
Q1. What are flippases?
Q2. Give an example of a flippase enzyme.
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Biological Membranes
Membrane Dynamics: Certain Integral proteins mediate cell-cell interactions
Several families of integral proteins in the plasma membrane provide specific points of attachment
between cells, or between a cell and extracellular matrix proteins.
Q1. Give four examples of integral proteins that are
involved in cell-cell interactions.
Q2. Diagrammatically show four different types of
integral proteins.
Biological Membranes
Membrane Dynamics: Interaction of plasma membranes with ECM
The extracellular matrix (ECM) is a collection of extra-cellular molecules secreted by cells that
provides structural and biochemical support to the surrounding cells.
In biology, the extracellular matrix (ECM) is a
collection of extracellular molecules secreted by
cells that provides structural and biochemical
support to the surrounding cells. Because
multicellularity evolved independently in different
multicellular lineages, the composition of ECM
varies between multicellular structures.
http://apbiocellorganelles.weebly.com/ecm.html
Common functions of ECM:
(i) cell adhesion; https://www.researchgate.net/figure/284728652_fig5_Figure-1-The-combinatorial-extracellular-matrix-ECM-of-bone-A-range-of-biological
Q1. What is extracellular matrix (ECM)?
(ii) cell-to-cell communication; Q2. What are the common functions of ECM?
(iii) cell differentiation. Q3. Does bone have extracellular matrix?
No question in the exam from the images of this slide.
Biological Membranes
Membrane Dynamics: Membrane fusion in biological processes
Membrane fusion: In membrane biology, fusion is the process by which two initially distinct lipid
bilayers merge their hydrophobic cores, resulting in one interconnected structure. Membrane fusion is
central in many biological processes.
Endomembrane: These membranes divide the cell into
functional and structural compartments, or organelles.
Although membranes are stable, they are by no means
static. Within the eukaryotic endomembrane system
(which includes the nuclear membrane, endoplasmic
reticulum, Golgi, and various
small vesicles), the membranous compartments
constantly re-organize. Vesicles bud from the
endoplasmic reticulum to carry newly synthesized lipids
and proteins to other organelles and to the plasma
membrane. Exocytosis, endocytosis, cell division, fusion
of egg and sperm cells, and entry of a membrane-
enveloped virus into its host cell all involve membrane
reorganization in which the fundamental operation is
fusion of two membrane segments without loss of
continuity (Fig. 11–23).
Certain proteins on cell membranes known as fusion
proteins facilitate the process of membrane fusion in
biological systems.
Q1. What is membrane fusion?
Q2. Give seven examples of membrane fusion.
Q3. What is the function of fusion proteins during membrane fusion?
Biological Membranes
Membrane Dynamics: Membrane fusion types
Membrane fusion between lipid bilayers: Fully fused and Hemifused.
Q1. Diagrammatically show hemi-fused and fully fused lipid bilayers.
Q2. Name a protein that is involved in exocytosis.
No question in the exam from the images of this slide.
Biological Membranes
Solute transport across membranes
Every living cell must acquire from its surroundings the raw materials for biosynthesis and for energy
production, and must release to its environment the byproducts of metabolism.
A few nonpolar compounds can dissolve in the lipid bilayer and
cross the membrane unassisted, but for polar or charged
compounds or ions, a membrane protein is essential for
transmembrane movement. In some cases a membrane protein
simply facilitates the diffusion of a solute down its
concentration gradient, but transport often occurs against a
gradient of concentration, electrical charge, or both, in which
case solutes must be “pumped” in a process that requires
energy (Fig. 11–26). The energy may come directly from ATP
hydrolysis or may be supplied in the form of movement of
another solute down its electrochemical gradient with enough
energy to carry another solute up its gradient. Ions may also
move across membranes via ion channels formed by proteins,
or they may be carried across by ionophores, small molecules
that mask the charge of the ions and allow them to diffuse
through the lipid bilayer. With very few exceptions, the traffic of
small molecules across the plasma membrane is mediated by
proteins such as transmembrane channels, carriers, or pumps.
Within the eukaryotic cell, different compartments have
Figure 15-1 A pure artificial phospholipid bilayer is
different concentrations of metabolic intermediates and
permeable to small hydrophobic molecules and small products and of ions, and these, too, must move across
uncharged polar molecules. https://www.ncbi.nlm.nih.gov/books/NBK21626/ intracellular membranes in tightly regulated, protein-mediated
processes.
The phospholipid bilayer is slightly permeable to Q1. Mention the solutes that are freely permeable through phospholipid bilayer.
water and urea and impermeable to ions and to Q2. What is the most common method of transporting samll molecules across cell membrane?
Q3. Diagrammatically show permeability of small molecules that are hydrophobic or
large uncharged polar molecules. uncharged polar.
Biological Membranes
Solute transport across membranes: Electrochemical Gradient
When two aqueous compartments containing unequal concentrations of
a soluble compound or ion are separated by a permeable divider
(membrane), the solute moves by simple diffusion from the region of
higher concentration, through the membrane, to the region of lower
concentration, until the two compartments have equal solute
concentrations (Fig. 11–27a).
When ions of opposite charge are separated by a permeable
membrane, there is a transmembrane electrical gradient, a membrane
potential, Vm (expressed in volts or millivolts). This membrane
potential produces a force opposing ion movements that increase Vm
and driving ion movements that reduce Vm (Fig. 11–27b).
The direction in which a charged solute tends to move spontaneously across a membrane depends on
both:
(1) the chemical gradient (the difference in solute concentration); and
(2) the electrical gradient (Vm) across the membrane.
Together, these two factors are referred to as the electrochemical gradient or electrochemical potential.
This behavior of solutes is in accord with the second law of thermodynamics: molecules tend to
spontaneously assume the distribution of greatest randomness and lowest energy.
The electrochemical gradient consists of two parts, the chemical gradient, or difference in solute
concentration across a membrane, and the electrical gradient, or difference in charge across a membrane.
Q1. What is electrochemical gradient?
Q2. Diagrammatically explain the factors that create electrochemical gradient.
Biological Membranes
Solute transport across membranes: Types of Transport across Membranes
Examples of transport types across cells membrane:
Transport type Mechanism Example
name
Simple diffusion Down concentration Gases: O2, CO2, N2;
gradient Small uncharged
polar molecules:
ethanol
Facilitated Down electrochemical Quick transport of
diffusion gradient water by
Aquaporins
Primary active Against electrochemical Maintaining low
transport gradient Na+ ion
concentration
inside the cell by
Na+K+ ATPases
Secondary active Against electrochemical Lactose transporter
transport gradient: driven by ions of E. coli
moving down its gradient
Ion channel Down electrochemical Voltage-gated Na+
gradient; may or may not be channels of
gated by a ligand or ion neurons
Ionophore- Down electrochemical Valinomycin, a
mediated ion gradient peptide ionophore
transport that binds K+
Q1. Draw a diagram to show the six different transport types
across cell membranes.
Q2. Give one example of each of the six different transport types
across cell membranes.
Next Lecture:
Bio-Signaling;
Bioenergetics
Reference Textbook:
Lehninger Principles of Biochemistry
4th or 5th Edition
Chapter 12, 13
David L. Nelson, Michael M. Cox
WH Freeman & Company,
New York, USA
