BIOMEMBRANES

Transport of the substance

through the cell membrane
 BIOMEMBRANES STRUCTURE

 The surfaces of cell

membranes are hydrophilic
(water-loving); the interiors
are hydrophobic.

 Hydrophilic molecules tend

to interact with water and
with each other.
Hydrophobic molecules
avoid interaction with water
and tend to interact with
other hydrophobic
molecules.
 Components and Properties of
Biological Membranes

 Biological membranes are thin, flexible surfaces separating

cells and cell compartments from their environments.
 Different membranes have different properties, but all share a
common architecture. Membranes are rich in phospholipids,
which spontaneously form bilayer structures in water.
 Membrane proteins and lipids can diffuse laterally within the
membrane, giving it the properties of a fluid mosaic.
 Membranes are asymmetric; interior and exterior faces carry
different proteins and have different properties.
Components and Properties of
Biological Membranes
 Components and Properties of
Biological Membranes
• Cholesterol
A steroid widely distributed in all living things. Cholesterol and other a steroids are found in
most membranes; they do not form bilayers, but dissolve in the lipid layer. Steroids can
account for up to 50% of the lipids in some cell membranes, and are thought to strengthen
the membrane and make it less sensitive to lysis.

• Glycoprotein
A protein containing short carbohydrate chains. In membranes, these proteins usually face
the exterior of the cell. The sugars mannose, galactose, and several others are common in
membrane glycoproteins. Many different spatial combinations of these sugars are possible,
resulting in many different surface markers or antigens, which are used as signals to
distinguish different cells.

• Integral protein
A membrane protein that has at least one segment anchored within the lipid bilayer. Many
integral proteins contain sequences of about 20 hydrophobic amino acids that fold into a
hydrophobic alpha-helix that is embedded in the lipid bilayer. In this shape, the
hydrophobic amino acid side chains form hydrophobic bonds with the fatty acid portion of
the phospholipids in the bilayer.
• Lipid bilayer nonpolar region
Phospholipids spontaneously assemble into lipid bilayers, with a characteristic
thickness of 4-5 nm. In cell membranes, the two hydrophobic fatty acid side
chains that form the "tails" of the hairpin-shaped phospholipid molecules are
oriented to the interior of the membrane.

• Peripheral protein
A membrane protein found on either the inner or outer face of the bilayer.
Peripheral proteins bind either to integral proteins or to the polar head groups
of membrane phospholipids.

• Polar phospholipid head groups

The hydrophilic (water-attracting) phosphate groups of phospholipids. These
groups interact with water by forming many hydrogen bonds. Each
phospholipid also has hydrophobic (water-repelling) fatty acid chains that
form the "tails" of the hairpin-shaped molecule. Phospholipids spontaneously
assemble into lipid bilayers, with a characteristic thickness of 4-5 nm.
 The membrane proteins and carboydrates occur
in combination with proteins and lipids , in
form of glycoproteins and glycolipids.
 The ‘glyco’ portion of these molecules is
located to the outside of the cell, dangling
outward fro the cell surface.
 The entire surface of the cell has a loose
carbohydrate coat called the glycolalyx , having
the following properties:
 Glycocalyx properties
 Many of the glycocalyx compounds ar negatively
charged, giving an overall negative surface of the
membrane.
 The cells could attach each other by means of their
glycocalyx.
 Some carbohydrates act as receptors for binding the
hormones like insulin that stimulate specific types of
activity in the cell.
 Some carbohydrates take part at the immune system
reactions.
 The lipid-protein interaction determine the
organization of molecules in membrane

 The attraction and repulsion electrostatic

forces between the ionized groups.
 The dispersing forces Van de Waals-London
which may turn to hydrophobic interactions.
 Hydrogen bonds assuring the hydrophilic
interactions.
 Fluid mosaic model
 According to the fluid mosaic model of S. J. Singer and Garth Nicolson
1972, the biological membranes can be considered as a two-dimensional
liquid where all lipid and protein molecules diffuse more or less freely. At
20º C the system is fluid.

 This picture may be valid in the space scale of 10 nm. However, the
plasma membranes contain different structures or domains that can be
classified as (a) protein-protein complexes; (b) lipid rafts, (c) pickets and
fences formed by the actin-based cytoskeleton; and (d) large stable
structures, such as synapses or desmosomes.

 The fluid mosaic model can be seen when the membrane proteins of two
cells (e.g., a human cell and a mouse cell) are tagged with different-
coloured fluorescent labels. When the two cells are fused, the two colours
intermix, indicating that the proteins are free to move in the 2D plane.
Proteins in the cell membranes may be integral or peripheral. Peripheral
proteins are present on only one side of the membrane, and integral
proteins span the entire membrane.
 MOVEMENT OF THE COMPONENTS

FLIP-FLOP

SLOW CHANGE

RAPID DIFFUSION
Cell Membrane
 Isolates the cell’s contents from
the external environment.
 Regulates exchange of substance
across the membrane.
 Communicates with other cells.
 Creates attachments within
andbetween cells.
 Regulates many biochemical
reactions
Isolate Cell Contents
 The cell is surrounded by an external
aqueous environment.
 The cell’s interior, the cytosol, is
composed mostly of water.
 Spontaneous arrangement of the lipid
bilayer:
– Hydrophilic heads outside (interacting
with water)
– Hydrophobic tails inside (interacting
with themselves)
 Most substances contacting the cell
membrane are hydrophilic and cannot
penetrate the
hydrophobic interior of the membrane.
Cholesterol Benefits
Protein Mosaic
Membrane Structure
within the Membrane
 Makes the bilayer
 Five major types of
– Stronger proteins:
– More flexible  – Receptor proteins
– Less fluid at high  – Recognition proteins
temperatures  – Enzymatic proteins
– Less solid at low  – Attachment proteins
temperatures
 – Transport proteins
– Slows phospholipid
movement
– Less permeable to water-
soluble substances
ASSYMMETRY OF BIOMBRANES: glycolipids and
glycoproteins towards the exterior
Cross section view of the structures that can be formed
by phospholipids in aqueous solutions
 Probably the most important feature of a biomembrane
is that it is a selectively-permeable structure.
 This means that the size, charge, and other
chemical properties of the atoms and molecules
attempting to cross it will determine whether they
succeed to do so.
 Selective permeability is essential for effective
separation of a cell or organelle from its surroundings.

 Therefore, the membrane play a major role in

transformig the metabolic energy in osmotic, electric or
mechanical work, in receiving and performing the
information.
Transport though the cell membrane
 Two types of transport:
1. Pasive- the mechanism of random molecular
movement of substances either through openings in
the membrane or in combination with a carrier
protein, without needing any energy.
2. Active- the echanism of movement of substances
through the membrane in combination with a carrier
protein and additionally against an energy gradient.
 Movement across the Membrane Responds to
Gradients:
• Concentration: the number of molecules of a
substance in a given volume of fluid.
• Gradient: physical difference between two
different regions of space.
– Temperature, concentration, pressure, etc.
– Cells use energy and their cell membranes
to generate concentration gradients
 Transport by simple diffusion
 The term simple diffusion refers to a process whereby a substance passes
through a membrane without the aid of an intermediary such as a integral
membrane protein.

 The force that drives the substance from one side of the membrane to the
other is the force of diffusion.

 In order for substances to pass through a cell membrane by simple diffusion it

must penetrate the hydrophobic core of the phospholipid bilayer.

 The types of molecules that can do this are themselves substantially

hydrophobic in nature such as carbon dioxide, oxygen or ethanol.

 Passive Transport (no energy required)

•Simple Diffusion
•Facilitated Diffusion
•Osmosis
 Simple diffusion

By the concentration gradient, the substance move from the compartment with
higher concentration to the compartment with smaller concentration.
 In the figure ,the green triangle
indicates a concentration gradient
of carbon dioxide.
 The blue arrow indicates the
direction of net flow of carbon
dioxide.
 The carbon dioxide penetrates the
phospholipid bilayer without the
aid of an intermediary molecule.
 You should be aware that the
relative sizes of the molecules in
this figure are not correct.
 The carbon dioxide molecules are
much smaller than the
phospholipids.
 No energy needed
• Small molecules take
advantage of the
selective permeability
of the membrane.
• O2, CO2, H2O
• Lipid-soluble molecules
 Fick’s Laws of diffusion
 Fick's First Law relates the diffusive flux to
the concentration field, by postulating that the
flux goes from regions of high concentration
to regions of low concentration, with a
magnitude that is proportional to the
concentration gradient (spatial derivative).
 Fick's First Law

dm dc dm T
  DS  ;D ~
dt dx dt M
The flux of matter across the surface is directly
proportional with the surface area S and with the gradient
of concentration.
D= diffusion coefficient, Ф= flux of matter, m = mass of
substances diffusing through the X direction, T=
temperature in Kelvin, M= molecular weight of the
diffused substance.
Diffusivity or diffusion coefficient
For spherical particles of radius r, Stokes' law gives

kT
D [D]= m2/sec
6 r
T= Temperature in Kelvin, K= Boltzmann constant,
η is the viscosity of the medium
Diffusion coefficient depends on the temperature, volume and the size and
shape of the particles.
 Fick's Second Law
Fick's second law predicts how diffusion causes the concentration
field to change with time:

2
dc d c
 D 2
dt dx
The temporary variation of the concentration in any solute point is
proportional with the space variation of the concentration gradient.
Particles diffusion trough the membrane
 If two compartments are separated by a permeable
membrane and contain solutions of the same
substance but in different concentrations, then the
concentration gradient is felt almost exclusively by
the thick of the membrane.
Particles diffusion trough the membrane

m c m
 D S sau   P S c
t x t
Where P= coefficient of permeability P = D/x, x = membrane’s thick.
For molecules of equal size, the one with greater solubility in lipids will pass
more quickly into the cell. For molecules of equal solubility, smaller ones
penetrate faster.
Permeability coefficient
 Facilitated Diffusion
• Small molecules and ions diffuse across the
membrane with the help of channel and/or
carrier proteins.
 – Channel proteins create hydrophilic channels

for ions.
– Carrier proteins have receptors to recognize
certain small molecules
Channel Carrier
Facilitated Diffusion
 Polar molecules and charged ions are dissolved in water but they can not diffuse
freely across cell membranes due to the hydrophobic nature of the phospholipids
that make up the lipid bilayers.

 Only small nonpolar molecules, such as oxygen can diffuse easily across the
membrane.
 All polar molecules are transported across membranes by proteins that form
transmembrane channels. These channels are gated so they can open and close, thus
regulating the flow of ions or small polar molecules. Larger molecules are
transported by transmembrane carrier proteins, such as permeases that change their
conformation as the molecules are carried through, for example glucose or
amino acids.

 Non-polar molecules, such as retinol or fatty acids are poorly soluble in water.
They are transported through aqueous compartments of cells or through
extracellular space by water-soluble carriers as retinol binding protein.

 The metabolites are not changed because no energy is required for facilitated
diffusion. Only permease changes its shape in order to transport the metabolites.
The form of transport through cell membrane which modifies its metabolites is the
group translocation transportation.
 IONOPHORES
 An ionophore is a lipid-soluble molecule usually
synthesized by microorganisms to transport ions
across the lipid bilayer of the cell membrane. The
ionophores are antibiotics.
 Ionophores disrupt transmembrane ion concentration
gradients, required for the proper functioning and
survival of microorganisms, and thus have antibiotic
properties. They are produced naturally by certain
microbes and act as a defense against competing
microbes.
 IONOPHORES- valinomycin

The structure of
valinomycin-K+ complex.

It functions as a potassium-specific transporter and facilitates the movement of

potassium ions through lipid membranes "down" an electrochemical potential gradient.
The stability constant K for the potassium-valinomycin complex is 106 and for the
sodium-valinomycin complex only 10. This difference is important for maintaining the
selectivity of valinomycin for the transport of potassium ions (and not sodium ions) in
biological systems. Other ionophores: gramicidin (H+, Na+, K+) , Ionomycin (Ca2+) ,
Nigericin (K+, H+, Pb2+) ….
Carrier Ionophores
 Endocytosis
 Endocytosis is the process by which cells absorb
molecules (such as proteins) from outside the cell by
engulfing it with their cell membrane.
 It is used by all cells of the body because most
substances important to them are large polar molecules
that cannot pass through the hydrophobic
plasma membrane or cell membrane.
 The process opposite to endocytosis is exocytosis.
 PINOCYTOSIS
In cellular biology, pinocytosis ("cell-drinking", "bulk-phase
pinocytosis", "non-specific, non-adsorptive pinocytosis", "fluid
endocytosis") is a form of endocytosis in which small particles are
brought into the cell suspended within small vesicles which
subsequently fuse with lysosomes to hydrolyze, or to break down, the
particles .
 Glucose transporter
 Glucose is an essential substrate for the metabolism of most cells. Because glucose
is a polar molecule, transport through biological membranes requires specific
transport proteins.

 Facilitated diffusion of glucose through the cellular membrane is otherwise

catalyzed by glucose carriers (protein symbol GLUT, SLC2 for Solute Carrier
Family 2) that belong to a superfamily of transport facilitators including organic
anion and cation transporters, yeast hexose transporter, plant hexose/proton
symporters, and bacterial sugar/proton symporters.

 Molecule movement by such transporter proteins occurs by facilitated diffusion.

This makes them energy independent, unlike active transporters which often require
the presence of ATP to drive their translocation mechanism, and stall if the
ATP/ADP ratio drops too low.

 Transport of glucose through the apical membrane of intestinal and kidney epithelial
cells depends on the presence of secondary active Na+/glucose symporters, SGLT-1
and SGLT-2, which concentrate glucose inside the cells, using the energy provided
by cotransport of Na+ ions down their electrochemical gradient.
Glucose transporter