SUPRAMOLECULAR ORGANIZATION

1. CELL MEMBRANE
The plasma membrane (or cell membrane) is a complex structure with complex functions: a lipid bilayer
with hydrophobic parts inward and hydrophilic to the outside, which gains its full functionality thanks to
proteins and carbohydrates embedded in it.

A space-filling model of an idealized

view showing regular structures.

Electron micrograph showing the

bilayer structure.

PLASMA MEMBRANE
The functions of the plasma membrane are to separate the cellular content from the external
environment, supporting the exchange of water, nutrients and waste products selectively. It presents
functions of transport, signaling, recognition, cell support, compartmentalization in eukaryotes and
electrical excitability (neurons and muscle fibers). Thus regulates the exchange of matter, energy and
information of the cell with the environment.
The basic structure of the membrane is a lipid bilayer that acts as a dynamic barrier, leaving the role of
effectors of membrane functions for proteins: transporters, enzymes, receptors, etc. The lipid bilayer
must be fluid so that lipids and proteins can move laterally in the bilayer, key aspect in the functionality
of the whole membrane.
COMPONENTS OF THE PLASMA MEMBRANE
• LIPIDS: mainly composed of phospholipids (major), glycolipids (minor) and cholesterol (great
importance in animal cells). Since they are amphipathic molecules with polar (hydrophilic) and apolar
(hydrophobic) parts, they have a bilayer arrangement with the hydrophobic parts facing each other
and the hydrophilic parts oriented towards the aqueous medium. It is a sealed bilayer, so it defines an
interior volume.
• MEMBRANE PROTEINS: proteins that interact with the plasma membrane, either through the
hydrophilic faces (extrinsic or peripheral proteins) or through the hydrophobic part (intrinsic or
integral proteins). Therefore, proteins must also have amphipathic: hydrophilic parts and / or
hydrophobic parts. The integral proteins constitute 50% approx. Of the total membrane proteins and
are usually glycoproteins (with chemical modifications that incorporate specific sugars). To extract
them from the membrane, drastic techniques are needed (strong interaction with lipids). Peripheral
proteins are easily extractable due to their weak interaction with lipids.
• MEMBRANE GLUCOSE: Linked to lipids or proteins from the outside of the membrane, forming
the glycocalyx or cell cover . Intervenes in communication processes and cell recognition. In animal
tissues, embedded in the extracellular matrix (for effects, comparable to the plant wall): secretion
product composed of carbohydrates and glycoproteins involved in providing tissue cohesion and
facilitating cells communication.

ENDOMEMBRANE SYSTEMS IN EUKARYOTES

Complex system of vesicles and flattened bags, covered
by membranes and widely communicated with each
other. They occupy a very substantial part of the
cytoplasm of animal cells, thus defining internal
cytoplasm and cytoplasm external to the endomembrane
system. The endomembranes are derived from the
plasma membrane, so they have a fluid mosaic structure.
The three main endomembrane systems are the
endoplasmic reticulum (protein synthesis and
maturation, transport, detoxification, lipid synthesis,
etc.), the Golgi apparatus (formation of primary
lysosomes and secretion) and the nuclear membrane
(delimits the nuclear space, in communication with the
RER).

CHARACTERISTICS OF BIOLOGICAL MEMBRANES

Lisophospholipids, detergents, soaps and fatty acids. Glycerophospholipids, sphingomyelins and

sphingoglucolipids.
Spontaneous sealing; Impermeable to ions and polar substances (but permeable to water)

PLASMA MEMBRANE MODEL (FLUID MOSAIC)

Plasma membrane model (fluid mosaic, Singer and Nicolson, 1972): lateral displacement of lipids and
proteins to attend specialized functions (cell-to-cell signaling, apoptosis, cell division, membrane
budding, cell fusion, etc.).
The asymmetric distribution of phospholipids in the membrane is characteristic of different cell types, as
an additional mechanism of regulation of membrane activity due to variations in fluidity. This is possible
thanks to the flip-flop movement (transversal diffusion of lipids).

Usual lipids: Glycerophospholipids, glycosphingolipids, sphingomyelins and cholesterol.

PLASMA MEMBRANE FLUIDITY

• Fluid mosaic model states that a membrane is a fluid structure with a “mosaic” of various proteins
embedded in it.
• Membrane fluidity is due to several factor:
- TEMPERATURE: lipids move around more with
increased temperature.
- LIPID PACKING: lipids with shorter fatty acids tails are
less stiff.
- SATURATION OF FATTY ACIDS: more C=C bonds
(more unsaturated) increase fluidity.
- CHOLESTEROL: decreases fluidity at warmer
temperatures; increases fluidity at lower temperatures.
FACTORS AFFECTING THE DEGREE OF MEMBRANE FLUIDITY
• Temperature: at higher temperatures, the membrane has more
fluidity than at lower temperatures.
• Tail length: longer fatty acid tails allow for more intermolecular
interactions between phospholipids, leading to less fluidity.
• Degree of unsaturation: Unsaturated fatty acids have one or more
double bonds in the fatty acid tails. Double bonds lead to a "bend",
pushing the adjacent phospholipids further apart. The increased
spacing reduces the number of intermolecular interactions and
increases fluidity.
• Cholesterol: the presence of cholesterol in the phospholipid bilayer
affects fluidity depending on the temperature. It acts as a buffer:
- High temperature: cholesterol decreases fluidity
- Low temperature: cholesterol increases fluidity

FLUIDITY OF THE MEMBRANE: EFFECT OF TEMPERATURE

The plasma membrane is fluid:

experimental demonstration

EFFECT OF THE COMPOSITION

Lipid Melting Point (Tm): T of transition from ordered crystalline state to fluid state. Acyl chains are
packed together in crystalline form (Van der Waals bonds)
MEMBRANE DYNAMICS
Phospholipids can move around and switch positions: (1)
laterally, (2) rotate, (3) flex their fatty acid chains and (4)
flip-flop (via enzymes called flipases). The more
phospholipids, the less mobility they have and the less
permeable the membrane is (imagine being in a crowded
room versus in a half full one!).

TRANSVERSE DIFFUSION OF LIPIDS

The asymmetric distribution of phospholipids in the plasma membrane causes the extracellular face to
have greater richness of glycolipids (signaling) and the cytosolic face has a greater richness of negatively
charged phospholipids (compared to the ER as an endomembrane), essential in the production of an
electrical potential difference in the membrane that will be .

2. PERMEABILITY OF THE MEMBRANE

Diffusion is a process resulting from random motion of molecules by which there is a net flow of matter
from a region of high concentration to a region of low concentration. Diffusion is driven by a gradient in
chemical potential of the diffusing species.
A change in concentration over a distance is called a concentration gradient. When two
compartments are divided by a permeable membrane, there is a net flux of molecules from the more
concentrated compartment to the less concentrated, that stops when equilibrium is reached.

CHEMICAL GRADIENT ELECTRIC GRADIENT

The plasma membrane has selective permeability of solutes, so
that it is practically impermeable to large uncharged polar
molecules and ions, but permeable by passive diffusion (from where
there is a higher concentration to where there is less concentration
of the solute in question) for hydrophobic molecules of small size
and small uncharged molecules.

PASSIVE TRANSPORT
The kinetics followed by the membrane proteins responsible for
facilitated transport in their interaction with the ligands
(maximum transport speed /affinity for the ligand to be
transported) fits to the enzymatic model described by Michaelis
and Menten. Passive transport follows a linear relationship with
the concentration difference across the membrane (gradient)

PASSIVE AND ACTIVE TRANSPORT

The solutes for which the membrane is impermeable must be transported through the membrane by
specific transporters (transmembrane proteins) that allow this transport by facilitated diffusion (same
base as the passive one, but with the participation of the transporter) or by active diffusion (with ATP
expense, against gradient). The transporter can facilitate uniport-type movements by transporting only
one molecule, or symport-type, transporting two types of molecule at the same time on the same side of
the membrane, or antiport-type, transporting two solutes at the same time in opposite directions.
ATP SYNTHASE: F0 AS EXAMPLE OF FACILITATED DIFFUSION

GLUT1 PROTEINS: EXAMPLE OF UNIPORT-TYPE FACILITATED DIFFUSION

GLUT are transporters related to facilitated diffusion. They allow glucose transport from the bloodstream
inside the cell.

ACTIVE TRANSPORT
Primary active transport involves the transport of a ligand
against the gradient with ATP expenditure. The secondary
active transport is that in which a second solute is
transported by a second transporter thanks to the action of
a coupled active primary transport.
PRIMARY ACTIVE TRANSPORT: the Na+ / K+ pump
Hydrolysis of ATP is coupled to a transport into the cell of a molecule (usually against a concentration
gradient), through the action of a primary transporter such as the Na+/K+ ATPase.

SECONDARY ACTIVE TRANSPORT

The ion gradient set up by the Na+, –K+, ATPase can be used to move molecules into the cell, through
the action of a secondary transporter such as the Na+ -glucose symporter.

GIBBS - DONNAN BALANCE

It is the balance that occurs between the ions that can pass
through the membrane and those that are not able to do so (for
example DNA or proteins with negative charge at physiological
pH). The compositions at equilibrium are determined both by
the concentrations of the ions and by their charges. The
negatively charged proteins attract positively charged ions and
repel negatively charged ions (see figure). As a consequence, an
electric gradient and two concentration gradients of the ions are
established. These ions are equal and of opposite sign.
In the equilibrium, the products of the ionic concentrations
of each side of the membrane are equal, so that the
concentration of particles is unequal on both sides of the
membrane and an osmotic gradient is established in the
direction towards the compartment containing the
proteins. To avoid this, there is a continuous pumping of
ions from the inside to the outside of the cell to reduce the
osmotic pressure and prevent the cell from exploding. In
the cells there is a pump that expels Na + with ATP
expenditure. Although the pump also imports K +, for every
three Na + that it ejects, it imports two K +. This also has
another consequence and is that there is an unequal load exchange
between both sides of the membrane, which contributes to
generating the membrane potential.

MEMBRANE POTENTIAL
As a result of the selective permeability of the plasma membrane,
the presence inside the cell of ions or negatively charged molecules
that do not diffuse, and the action of several sodium-potassium
pump units, there is an unequal distribution of charges across the
cell membrane. As a result, inside the cell there are more negative
charges compared to the outside. This charge difference results in a
potential difference that is known as the membrane potential.

RESTING MEMBRANE POTENTIAL

The voltage (charge) difference between the intracellular and extracellular fluid, when the cell is at rest (i.e
not depolarized by and action potential).

Mechanisms responsible for the resting membrane potential:

• Chemical gradients generated by active transport pumps: the concentration of ions are significantly
different between the intracellular and extracellular fluid, eg. the ratio of potassium ions is 35:1.
 • Selective membrane permeability: the cell membrane is selectively ion- permeable, specifically it is
much more permeable to potassium ions.
• Electrical gradients are generated because potassium leak (via K2P channels) from the intracellular
fluid creates a negative intracellular charge. This charge attracts potassium ions back into the cell
and thus opposes the chemical gradient.
• Electrochemical equilibrium develops when electrical and chemical forces are in balance for each
specific ion species, and this is described by the Nernst equation.
• The Nernst potential for each ion is the transmembrane potential difference generated when
that ion is at electrochemical equilibrium.
• At rest, with normal intracellular and extracellular electrolyte concentrations, the net charge of the
intracellular side of the cell membrane is negative and is approximately -70 to -90 mV for
mammalian neurons

RESTING MEMBRANE POTENTIAL OF A NEURON

The membrane potential of an inactive or resting neuron is called the resting membrane potential (RMP)
or resting potential (measured in millivolts). It refers to the unequal concentrations of electrical charge
between the interior and exterior of a cell when it is at rest.

MEMBRANE POTENTIAL: NERNST EQUATION

In a cell where the RMP is equal to the equilibrium potential when the rate at which ions leave the cell is
the same as the rate at which ions enter the cell, the RMP is calculated using the Nernst equation:
Considering the cell, on either side of the plasma membrane there are several ions and not all of them
have the same permeability (this is not what is assumed in the
equilibrium equations). The greater the permeability of the
membrane to a given ion, the greater the contribution of
that ion to the genesis of a membrane potential. The main
ions that can cross the membrane are K+, Na+ and Cl-. The
Nernst equation allow to calculate the electric potential (V)
difference necessary to produce a force that compensates
for the one caused by the concentration gradient of a given
ionic species.
This potential is known as the equilibrium potential of this
ionic species.

MEMBRANE POTENTIAL
Considering cells (nerve cells in particular), the permeability of the membrane for potassium is much
higher than the permeability for sodium, with the permeability for chlorine in values between both. This
explains why the membrane resting potential (-86mv) is close to the equilibrium potential of potassium
(-94mv) but below it. Sodium, being very little permeable, contributes much less to the generation of the
membrane potential, leaving its equilibrium potential (+ 55mv) very far from that of the membrane. The
potential of chlorine is very close to the membrane and in a situation close to equilibrium.
Under these circumstances, it tends to exit K+ and to enter Na+, the flow of chlorine being almost in
equilibrium.