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Membrane Structure and

Function

Transport of Substances through


the cell membrane
Chapter 2 (cell membrane parts) and 4 of Guyton and Hall, 11 th ed.

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• In the cell membrane are phospholipids,
proteins, sugars, etc., that separate intra
and extra cellular fluid, and limit what can
travel through it. Proteins create channels
or pores. They can be perceived as
antigens. There are some proteins that are
only on the inside of the cell membrane,
which turn on activities in the cell.

2
• Phospholipids are antipathic (water loving and water
hating). One side can attach to other water loving
molecules on the phosphate portion. The two fatty acid
(FA) tails are made of long chains of hydrocarbons. The
FAs dislike water, but can bind with hydrophobic
molecules. If we only had one layer of phospholipids, the
membrane would orient toward the water loving fluid. But
FAs don’t like the water, so with a bi-layer, the FA can be
happy, and the phosphate can be happy. Substances
that love lipids can get to the middle of the membrane,
but water loving has a hard time crossing.

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Membrane Function
• Organizes chemical activities
of cell
– separates cells from outside
environment
– controls passage of molecules
across membranes
– partitions organelle function in
eukaryotes
– provides reaction surfaces and
organizes enzymes and their
substrates
– Proteins embedded provide
function, too!
• Channels
• Carriers
• Receptors
• Cell adhesion
• Enzymes
• Identification markers, etc.

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Membrane Structure
– phospholipids have polar “head”
(hydrophilic) and nonpolar “tail”
(hydrophobic)
– form stable bilayer in water with
heads out and tails in
– hydrophobic interior from fatty
acid tails forms barrier to
hydrophilic molecules
– Chemistry: glycerol + two fatty
acids and phosphate head

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• Proteins can be integral (throughout the
membrane) or peripheral (one side or the other).
• Integral protein can create a pore, or channel
with a gate that can open and close. Proteins on
the surface of the membrane can bind a
chemical. A peripheral protein on the inside of the
membrane can instigate a series of enzymatic
reactions within the cell. Some proteins can bind
substances on the outside of the membrane and
transport them into cell (facilitative diffusion)
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Proteins:
•Provide function to a membrane
•Can move laterally
•membrane also shows “sidedness”
•interior - attachment to cytoskeleton
•exterior - carbohydrates, extracellular matrix (next slide)
• defined by mode of association with the lipid bilayer
– integral: channels, pores, carriers, enzymes, etc.
– peripheral: enzymes, intracellular signal mediators, etc.

K+ 7
• Sugars outside of the cell can attach to the phosphate
heads or to the proteins (that will now be a glycoprotein).
If there are many glucose molecules on the outside of
the cell, it will make the outside of the membrane
negatively charged. Every cell is set up like a battery,
with a separation of charges across the cell membrane.
This is called potential; one area is more negative than
another area. There is storage of electricity, like a
battery. The inside of the cell should be more negative
than the outside of the cell. But if there is a glycocalyx
(sugar bundle) on the outside of the cell, they make it a
negative charge.
8
Carbohydrates
•glycoproteins (majority of integral proteins)
• proteoglycans
•glycolipids (approx. 10%)
• involved in cell-cell attachments/interactions
• play a role in immune reactions

(-) (-) (-)


(-) (-)
GLYCOCALYX (-)
(-)

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• Cholesterol maintains the fluidity of cell membrane so the
lipids are not frozen in place, but not so much that there
are gaps in the cell membrane. There needs to be a
balance of flexibility and stability. Cholesterol is a lipid, so
it’s located in the middle of the membrane. If you try to
apply a lipid to a phospholipid membrane without proteins
in it, and you will see that hydrophobic molecules get
through it easier than hydrophilic. Gases like CO2, O2,
and small molecules like ethanol could get through. If you
try to add water loving molecules (charged molecules like
glucose and positive ions), they can pass. Water can also
get through. Water loving substances get across the lipid
center by active and passive transport.
10
Cholesterol:
• present in membranes in varying amounts
• increases membrane FLEXIBILITY and STABILITY
during different temperatures
• helps to increase hydrophobicity of membrane

(-) (-) (-)


(-) (-)
(-)
(-)

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Transport across a membrane:
Understand this!
LIPIDS by themselves are a:
• barrier to water and water-soluble substances
•Allow lipid soluble substances to cross through membrane

glucose CO2 O2
ions H2O N2

hydrophilic
“head”
hydrophobic
FA “tail”

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Movement across the cell Membrane
… but, in a living cell, hydrophilic molecules still get across! How?

CO2
ions H2O N2 O2
glucose

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Passive Transport Active Transport
• occurs down a concn. gradient • occurs against a concn. gradient
• no mediator (simple) • involves a “pump”
•or involves a “channel” or • requires cellular ENERGY
“carrier”(facilitated) (ATP)
• no additional energy beyond
kinetic energy

Osmosis &

Passive transport 14
Figure 4-2; Guyton & Hall
• Passive transport means no cellular
energy required, no ATP used.
• Active transport means ATP is used, either
directly or indirectly.
• Passive transport makes substances move
from high to low concentration, down their
gradient.
• Active transport is when at least one solute
is moved against its concentration
gradient.
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• Osmosis is passive, no ATP is used. Water
moves from high to low concentration. That is,
water moves from low particles to high particles.
If you have two sides of a membrane, and the
particles can’t move, water will move. How does
it get through? There are aqua pores created
just for water passage. You have to have a gene
to make these pores. The wrong amount of
pores causes water imbalances.

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Osmosis:
- net flow of water across a semipermeable
membrane (permeable to water but not solute)
Osmosis occurs from pure water toward a water/salt solution.
Water moves down its concentration gradient.

ne
embra
eable m
This movement is
affected by the erm
solute
ively p

concentration
(osmotic force)
Select

and hydrostatic
forces (more on
this later in the
course 17
Figure 4-9; Guyton & Hall
• When you did the PhysioEx osmosis activity,
you applied pressure, did not see volume
change, just measured the hydrostatic pressure.
• The idea of molarity and osmolarity is expressed
in this example:
• Solution A is 100 g of something added to water
• Solution B is 1000g added to water.
• The g% is different.

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• To calculate molarity, you have to divide grams by
molecular weight. Both of the above solutions have
same molarity, one mole per liter. That means they both
have the same number of molecules. They are different
sizes, but still the same number. If neither side
dissociates, same number of particles, but if A
dissociates into 3 particles, how many osmoles is it?
Three. If A is separated from B by a membrane that only
allows water to move, where will water go? It moves
from B to A, and the volume in A will climb, unless you
apply pressure (3osm) to stop it from rising. Molarity is
the number of molecules.
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Major determinant of osmotic pressure- differences in
total solute or particle concentration NOT MASS!
 

100 g 1000 g
in 1 L in 1L

Solute A Solute B
Mw = 100 Mw = 1000
Which has the greatest molar concentration?
Which has the greatest number of molecules?(6.02 x 1023 Molecules)
Which solution has the greatest osmolality? (assume no dissociation)
If “A” has a dissociation factor of 3, now which solution has the greatest osmolality?
mOsm (millisomolar) = index of the concn
or mOsm/L of particles per liter soln

mM (millimolar) = index of concn of


or mM/L molecules per liter soln 20
• Simple diffusion of a solute is also
passive. Rate of diffusion depends on
• How big is the gradient? How steep is the
slide? The greater the difference, the
faster the rate of diffusion, if the solute is
permeable across the gradient.
• Is the solute permeable?

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• Simple diffusion of small molecules can diffuse without any
protein assistance. Water loving larger molecule needs a
protein. Some pores are open all the time, and those that
can use it, will diffuse when they want. If always open, is
a pore. If not always open, it is a channel. Channels
are gated. The gate can be open or closed. They open
when a special chemical (ligand) binds to it, called ligand
operated channels (LOC), like a key. Some open by
electrical change, like garage door opener, called VOC
voltage operated channel. If it doesn’t have permeability,
gate closed, can only get through slowly. If it is open,
solute can diffuse. There is no ATP used, not active
transport.
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Non-carrier mediated transport
1. Simple Passive Diffusion
• is tendency of molecules to
spread out spontaneously from
area of high concentration to
area of low concentration
• At equilibrium, there is not net
gain nor loss of cell fluid.
• It is passive; molecule diffuses
down concentration gradient
without input of cellular energy
• Need permeability
• Need concentration gradient
(chemical/ electrical) Can a molecule move from side
B to side A?
Figure 4-8; Guyton & Hall 23
Simple Diffusion
(a) lipid-soluble molecules move readily across the membrane
(rate depends on lipid solubility)
(b) water-soluble molecules cross via channels or pores (these are
proteins!).
•ungated
•Gated channels- Chemical and Electrical gated channels
(c) Different molecules diffuse independently of each other
(a) (b)

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Voltage gated channel
• These cause a change in the electrical
potential (separation of charges). They are
specific, for instance, one may only allow
sodium to cross. You would need a different
one to allow potassium to pass. The amino
acids dictate what things can go through them.
Need many different types of proteins, many
pores.
• Ligand gated channel
• A chemical binds to open the gate.
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Ion Channels- allow simple diffusion

Characteristics:
ungated
• determined by size, shape, distribution of charge, etc.
gated
• voltage (e.g. voltage-dependent Na+ channels)
• ligand activated (e.g. nicotinic ACh receptor channels)

in

out
Na+ and other
Na+ ions 26
How was this
discovered?
• “Patch Clamp”
• Nobel Prize in Physiology & Medicine -1991
• Neher and Sakmann

in

out
Na+
• Facilitated diffusion is still passive, no ATP is used. It is the
same end result as simple diffusion. The difference is that it
requires a protein to physically bind to it and move it across
the cell membrane. Therefore, it can be saturated. The rate at
which solute is moved is limited by the number of carriers you have.
When drunken people in a bar want to go home when the bar
closes, and there is only one taxi, it would take a long time for all the
people to get home. To get home faster, need more carriers. If
each carrier moves one carrier, rest of molecules has to wait their
turn. If there are too many glucose molecules in the nephron, you
will reabsorb some of them them in the bloodstream, and some will
spill out in the urine. This is because glucose transporters are
saturated in the nephron.

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Facilitated Diffusion (also called carrier mediated diffusion)
• Specific proteins facilitate
diffusion across membranes
– no cellular energy required
– Carrier protein interacts with
solute
– Specificity – carrier only acts
upon specific substrates.
– Saturation – the rate of transport
will reach a maximum based on
the number of carriers available
in the membrane. (This is animated
on next slides)
Rate of diffusion is limited by
• Vmax of the carrier protein
• the density of carrier
proteins in the membrane
(i.e., number per unit area)

Figure 4-7; Guyton & Hall 29


=solute
= transporter
1
1/min
Ex. Pass-through 2
rate is 1 each
minute 2/min
3
3/min
4
4/min
5
5/min
Transport maximum is reached when carriers
are saturated, Vmax. 30
Rate of Simple vs. Facilitated Diffusion

• If you increase concentration gradient,


rate increases as well.
• Facilitative will reach velocity
maximum. When it is saturated, it levels
off.

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Simple vs. Facilitated
simple diffusion
rate of diffusion  (Co-Ci)
rate of
diffusion

Vmax
Tm facilitated diffusion

Concn of substance

What limits maximum rate of


facilitated diffusion? 32
Primary active transport
• This uses ATP directly. A protein whose name ends in
ATPase is one that hydrolyses ATP, creating a
concentration gradient. Going skiing, do you climb the
mountain? No, you take the lift, using the energy in the
chair lift. Ski down a slope with a rope around your waist,
that rope will pull up the next person. That provides the
stored energy to pull the second person up. This is
secondary active transport. The protein does not use
the ATP. As one goes down, liberates energy that
helps a different molecule to move against its
concentration gradient.

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Active Transport

Primary Active Transport Secondary Active


– molecules are “pumped” Transport
against a concentration – transport is driven by the
– gradient at the expense energy stored in the
of energy (ATP) concentration gradient of
another molecule (Na+)
– direct use of cellular
energy – One molecule down
gradient
– One molecule against
gradient
– indirect use of energy
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• Most ATPs are used for primary active transport.
The most common is sodium-potassium
ATPase. It moves two solutes against their
gradients. It keeps sodium outside and
potassium inside. When a channel is made, the
substance that comes first tells you the
protein has a preference for that substance.
Sodium-potassium ATPase moves 3 sodium ions
for every two potassium ions. They still need
carrier proteins. This job can only be done at a
certain rate.
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Primary Active Transport
• Cells expend energy for
active transport
– transport protein involved in
moving solute against
concentration gradient
– energy from ATP
– rate limited by Vmax of the
transporters
• up to 90% of cell energy
Na+/K+ ATPase
expended for active plays an important role in regulating osmotic
transport! balance by maintaining Na+ and K+ balance
requires one to two thirds of cell’s energy!
– active transport of two Others exist- calcium ATPase and H+ ATPase
solutes in opposite directions
often coupled
36
Secondary active transport
• ATP is not directly used by the protein. Three sodium
ions are kicked out, 2 potassium ions are pulled in.
• Another integral protein creates a protein, binds to
sodium, allowing it to move down the concentration
gradient. If it had high levels of glucose, it would pull in
glucose against its concentration gradient, and into the
cell. This Na-glucose system is a co-transporter. A co-
transporter takes two substances in the same
direction across the cell membrane. An anti-porter
takes two substances in opposite directions.

37
Secondary Active Transport
- co-transport and counter-transport -

1. Co-transport (co-porters): substance is


transported in the same direction as the “driver”
ion (Na+)
Examples:
outside
Na+ AA Na+ gluc Na+ 2 HCO3-

inside 38
2. Counter-transport (anti-porters): substance is
transported in the opposite direction as the “driver” ion
(Na+)

Examples:
outside
Na+ Na+ Na+/HCO3-

Ca2+ H+ Cl-/H+

inside 39
• Sample test questions: given the following list, answer the questions below.
• Osmosis
• Simple Diffusion
• Facilitative Transport
• Primary active Transport
• Secondary active Transport

• Which has net movement of water? Simple diffusion


• Select all that apply: This type of transport moves solutes down the
concentration gradient. Simple, facilitative, secondary,

• Which ones have a solute moved against its gradient: primary and
secondary
• Which is moved against its gradient and ATP is directly used: primary

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