3.

1 Membrane Structure and Composition

• Plasma membrane
• Encloses
intracellular
contents
• Selectively
permeable
• Responds to
changes in
cell’s
environment
3.1 Membrane Structure and Composition cont’d
• The plasma membrane - fluid lipid bilayer
embedded with proteins.
• Phospholipids
• Most abundant
membrane
component
• Head contains
negatively
charged
phosphate group
(hydrophilic)
• Two nonpolar
fatty acid tails
(hydrophobic)
3.1 Membrane Structure and Composition cont’d
• Phospholipids
• Assemble into lipid bilayer with hydrophobic
tails in the center and hydrophilic heads in
contact with water
• Fluid - phospholipids held together by van
der Waal’s forces
Optional HW Assignment
• In your own handwriting, define
• Organism
• Organ
• Organelle
• Turn your paper in in class on 2/1/2019
• Remember to write your whole name
legibly on your paper.
3.1 Membrane Structure and Composition cont’d
• Cholesterol
• between phospholipids; prevents
crystallization of fatty acid chains
• Maintains fluidity, esp. in cold
temperatures
• Decreases permeability, esp. in warm
temps
• Cold-induced rigidity is countered in
some poikilotherms by enriching
membrane lipids with polyunsaturated
fatty acids.
Cholesterol prevents fatty acids chains from
packing together, enhancing membrane fluidity.
3.1 Membrane Structure and Composition cont’d
• Membrane proteins
• Integral membrane proteins - embedded in
lipid bilayer
• hydrophilic and hydrophobic regions
• TM proteins extend through the entire
thickness of the membrane
• Peripheral proteins - found on inner or outer
surface of membrane
• Polar molecules
• Anchored by weak chemical bonds to polar
parts of integral proteins or phospholipids
 ▲

▲
▲
▲ ▲ ▲
▲ = Assorted membrane proteins
3.1 Membrane Structure and Composition cont’d
• Two models of membrane
structure
• Fluid mosaic model
• Membrane proteins float freely in a
“sea” of lipids.
• Membrane-skeleton fence model
• Mobility of membrane proteins is
restricted by the cytoskeleton
• Some proteins perform specialized
functions in specific areas of the
plasma membrane
3.1 Membrane Structure and Composition cont’d
• Membrane proteins
• Channels- enable ions to pass
• Carriers- transfer larger substances
• Receptors- bind specific molecules
• Docking-marker acceptors- inner surface
lock-and-key with secretory vesicles
• Enzymes – catalyze chemical reactions,
inner and outer membrane
• Cell adhesion molecules (CAMs)- help hold
cells together
• Self-identity markers- “self” recognition
3.1 Membrane Structure and Composition cont’d
• Membrane carbohydrates
• only on outer surface of
membrane
• Short-chain carbohydrates bound
to membrane proteins
(glycoproteins) or lipids
(glycolipids)
• Important in self-recognition and
cell-to-cell interactions
 ▲

▲ ▲

▲ = Assorted membrane carbohydrates

3.2 Membrane Transport
• The plasma membrane is selectively
permeable.
• Permeability across the lipid bilayer
by unassisted, simple diffusion
depends on:
• Lipid solubility
• Size
Transport processes
Protein involved?
Inherently energetically No Yes
favorable?
Yes Simple diffusion Facilitated diffusion
No - Active transport
3.2 Membrane Transport cont’d
• Two types of passive
transport:
1) Diffusion down a
concentration gradient
2) Conduction along an
electrical gradient
3.2 Membrane Transport cont’d
• Fick’s law of diffusion
• Rate of diffusion depends on:
• Concentration gradient
• Permeability of membrane to substance
• Surface area of membrane
• Molecular weight of diffusing substance
• Distance across which diffusion takes
place
• Temperature
3.2 Membrane Transport cont’d
• Two types of passive
transport:
1) Diffusion down a
concentration gradient
2) Conduction along an
electrical gradient
3.2 Membrane Transport cont’d
2) Conduction along an electrical
gradient
• Movement of ions across
membrane is affected by their
electrical charge.
• A difference in charge between
two adjacent areas produces an
electrical gradient.
3.2 Membrane Transport cont’d

• An electrical gradient passively

induces ion movement -- conduction
• Only ions that can cross the plasma
membrane can move down the
charge gradient.
• Ion conduction is faster than diffusion.
• A co-existing electrical and
concentration gradient is called an
electrochemical gradient.
Movement along an electrical gradient.
3.2 Membrane Transport cont’d
• Osmosis
• Water (a polar molecule) moves
across a membrane by osmosis, from
an area of lower solute concentration
to an area of higher solute
concentration.
• The water’s concentration gradient
provides the driving force.
Hypo- Hyperosmotic
osmotic

Solutions’
osmotic
properties are
framed in
terms of the
solute’s
concentration.
3.2 Membrane Transport cont’d
• Osmosis cont’d
• Hydrostatic pressure opposes
osmosis.
• Osmotic pressure is the pressure
required to stop the osmotic flow.
• Osmotic pressure is proportional to
the concentration of nonpenetrating
solute.
• a solution with high solute concentration
exerts greater osmotic pressure than
does a solution with a lower solute
concentration.
Example of
osmosis when
pure water is
separated from
a solution
containing a
nonpenetrating
solute.
3.2 Membrane Transport cont’d
• Colligative properties of solutes depend
solely on the number of dissolved particles
in a given volume of solution
1) Osmotic pressure
2) Elevation of boiling point
3) Depression of freezing point
4) Reduction of vapor pressure
3.2 Membrane Transport cont’d
• Tonicity refers to the effect of solute
concentration on cell volume
a) Isotonic solution (iso = equal)
b) Hypotonic solution (hypo = below)
c) Hypertonic solution (hyper = above)
3.2 Unassisted Membrane Transport

a) Isotonic solution
•Same
concentration of
nonpenetrating
solutes as in
normal cells
•Cell volume
remains constant.
3.2 Unassisted Membrane Transport

b)Hypotonic solution
•Lower solute
concentration
than in normal
cells
•Cell volume
increases,
perhaps to the
point of lysis.
3.2 Unassisted Membrane Transport

c) Hypertonic solution
• Higher solute
concentration
than in normal
cells
• Cell volume
decreases,
causing
crenation.
3.3 Assisted Membrane Transport
• Phospholipid bilayer is impermeable to:
• Large molecules (proteins, nucleic acids,
polysaccharides)
• Small, poorly lipid-soluble (e.g., glucose,
and amino acids)
• Small, charged molecules (ions)
3.3 Assisted Membrane Transport cont’d

• Mechanisms for
transporting these
molecules into or out of
the cell
1)Channel transport
2)Carrier-mediated transport
3)Vesicular transport
3.3 Assisted Membrane Transport cont’d
1) Channel transport
• Transmembrane proteins form narrow
channels
• Selective
• Permit passage of ions or water
(aquaporins)
• Gated channels can be open or
closed
• Leak channels are open at all times
• Movement through channels is faster
than carrier-mediated transport.
Aquaporin forming a channel through a membrane
3.3 Assisted Membrane Transport cont’d
2)Carrier-mediated transport
• Transmembrane proteins that
can undergo reversible
changes in shape.
• Binding sites can be exposed
to either side of membrane.
• Transport small water-soluble
substances
3.3 Assisted Membrane Transport cont’d
2) Carrier-mediated transport
• Carrier-mediated transport takes
two forms, depending on whether
energy is required to complete
the process:
a. Facilitated diffusion (passive)
b. Active transport (energy
required)
Facilitated
diffusion, a passive
form of carrier-
mediated transport
3.3 Assisted Membrane Transport cont’d

2)Carrier-mediated transport
• Characteristics of carrier-
mediated transport systems:
a) Specificity
b) Saturability
c) Subjection to competition
3.3 Assisted Membrane Transport cont’d

2) Carrier-mediated transport
• Characteristics of
carrier-mediated
transport systems:
b) Saturability -- limit to
the amount of a
substance that a
carrier can transport
in a given time
(transport maximum
or Tm)
3.3 Assisted Membrane Transport cont’d

2)Carrier-mediated transport
• Characteristics of carrier-
mediated transport systems
c) Competition -- closely related
compounds may compete for
the same carrier
3.3 Assisted Membrane Transport cont’d

• Facilitated diffusion
• Passive carrier-mediated
transport from high to low
concentration
• Does not require energy
• Example: Glucose
transport into cells (sometimes)
3.3 Assisted Membrane Transport cont’d
• Facilitated diffusion
• Molecule to be transported attaches
on binding site on protein carrier
• Carrier protein changes conformation,
exposing bound molecule to the other
side of the membrane (lower
concentration side)
• Bound molecule detaches from the
carrier
• Carrier returns to its original
conformation (binding site on higher
concentration side)
Facilitated
diffusion, a passive
form of carrier-
mediated transport
3.3 Assisted Membrane Transport cont’d

• Active transport
• Carrier-mediated transport
that moves a substance
against its concentration
gradient.
• Requires energy
• Two Types:
1) Primary active transport
2) Secondary active transport
3.3 Assisted Membrane Transport cont’d
• Active transport
1)Primary active transport
•Energy is directly
required
•Transporter directly splits
ATP to power the
transport process
Model for
active
transport.
From last week’s homework
3.3 Assisted Membrane Transport cont’d

• Na ,K -ATPase
+ + (pump)
• Pumps 3 Na+ out of cell for
every 2 K+ in
• Splits ATP for energy
• Phosphorylation induces
change in shape of
transport protein.
3.3 Assisted Membrane Transport cont’d

• Na+,K+-ATPase
• The Na+/K+-ATPase plays two
important roles:
1) Maintains Na+ and K+
concentration gradients
across the plasma membrane
of all cells
2) Helps regulate cell volume by
controlling the concentration
of solutes inside the cell
Na+/K+ pump
3.3 Assisted Membrane Transport cont’d

• Active transport
2) Secondary active transport
• ATP is not used directly
• Carrier does not split ATP,
uses energy stored in the
form of an ion
concentration gradient built
by primary active transport
3.3 Assisted Membrane Transport cont’d

• Secondary active transport

• Simultaneous transport of a substance and
an ion across the plasma membrane by a
cotransport protein
• One thing is transported against its
concentration gradient
• Driven by simultaneous transport of an
ion along its concentration gradient
• Example: Cotransport (aka symport) of
glucose and Na+ across the luminal
membrane of intestinal epithelial cells
Location of the
Na+/K+ pump in
epithelial cells of the
small intestine.
Na+/K+ pump uses
ATP to drive Na+
uphill out of epithelial
cell.
This Na+ gradient
drives the Secondary
Active Transport
The sodium and glucose
cotransporter uses the
Na+ gradient to
cotransport Na+ downhill
and glucose uphill from
lumen to cell
Both Na+ and glucose bind to SGLT
on luminal side.
The SGLT transport protein changes
shape . . .
And both glucose and Na+ are
released to the cell interior.
This secondary active
transport creates a
glucose concentration
gradient from the cell to
the blood.
Facilitated diffusion then
moves glucose passively
downhill into the blood
through the glucose
transporter (GLUT).
Announcement
• Table 3-2 Error
• Simple diffusion is classically understood
to be transport across a membrane that
does not require a protein intermediary.
• Therefore, diffusion through a protein
channel cannot be considered simple
diffusion.
3.4 Intercellular Communication
and Signal Transduction
• Intercellular communication can take
place directly or indirectly.
• Three mechanisms of direct intercellular
communication:
1) Gap junctions
2) Transient direct linkup of surface markers
3) Nanotubes
3.4 Intercellular Communication
and Signal Transduction cont’d
• Indirect intercellular communication
• Most common means of cell
communication.
• Intercellular chemical messengers
• An intercellular messenger is secreted by
a cell
• It binds with specific receptors on target-
cells.
• There are six different types of intercellular
signals
3.4 Intercellular Communication
and Signal Transduction cont’d
• Indirect intercellular communication
1) Paracrine
1) local chemical messengers, the effect of
which is exerted only on neighboring cells,
e.g., histamine
3.4 Intercellular Communication
and Signal Transduction cont’d
• Indirect intercellular communication
2) Neurotransmitters
• used by neurons which communicate
directly with the cells they innervate
3.4 Intercellular Communication
and Signal Transduction cont’d
• Indirect intercellular communication
3) Hormones
• long-range
chemical
messengers that
are secreted into
the circulation
• Blood carries the
messengers to
target cells.
3.4 Intercellular Communication
and Signal Transduction cont’d
• Indirect intercellular communication
4) Neurohormones
• hormones released into the circulation
by neurosecretory neurons
3.4 Intercellular Communication
and Signal Transduction cont’d
• Indirect intercellular communication
5) Pheromones
• chemical signals released into the
environment to reach sensory cells
of other animals
3.4 Intercellular Communication
and Signal Transduction cont’d
• Indirect intercellular communication

6) Cytokines
• regulatory
peptides
made by
almost any
cell; generally
involved in
development
and immunity

Illustration courtesy of barefacedtruth.com

3.4 Intercellular Communication
and Signal Transduction cont’d
• Signal transduction
• Extracellular chemical
messengers bind with receptors
to trigger a biochemical chain of
events inside the target cell.
• Signal transduction is the process
by which incoming signals are
conveyed to the target cell’s
interior for execution.
3.4 Intercellular Communication
and Signal Transduction cont’d
• Signal transduction
• Lipophilic (lipid soluble)
extracellular messengers
• Pass through the target cell’s
plasma membrane to bind to
intracellular receptors
• Produce second messenger (e.g.
nitric oxide, cyclic GMP )
• Alter gene transcription (e.g.
thyroid, retinoid and steroid
hormones)
3.4 Intercellular Communication
and Signal Transduction cont’d
• Signal transduction
• Lipophobic (water soluble)
extracellular messengers
• Can’t pass through the target cell’s
plasma membrane; bind with surface
membrane receptors as “first
messenger”
• Some receptors are channels
• Some are enzymes that
phosphorylate target proteins
• Some transfer the signal to an
intracellular second messenger
Types of receptors
according to mode
of action.
3.4 Intercellular Communication
and Signal Transduction cont’d
• Phosphorylating
enzymes
• Protein kinase
phosphorylates a
target cell protein
• Phosphorylated
protein changes
shape and function
3.4 Intercellular Communication
and Signal Transduction cont’d
• Phosphorylating enzymes
• Tyrosine kinase (e.g. insulin
receptor) phosphorylates its
own tyrosine residues
(autophosphorylation).
• Activated protein kinase sites
phosphorylate cytoplasmic
proteins to lead to the cellular
response.
3.4 Intercellular Communication
and Signal Transduction cont’d
• G-protein-coupled membrane receptors
(GPCRs)
• Inactive G-protein on inner surface of plasma
membrane contains α, β and γ subunits with a GDP
bound to the α subunit
• When hormone binds with its receptor, the receptor
interacts with the G-protein, causing the α subunit to
release GDP and acquire GTP.
• Activated, GTP-bound α subunit or the βγ subunit
links with an effector protein in the membrane and
alters its activity
• 300 different receptors use the G protein
mechanism
G-protein
coupled
receptor
3.4 Intercellular Communication
and Signal Transduction cont’d
• Cyclic AMP second-messenger GPCR
pathway
• Binding of hormone (first messenger) to its
receptor activates a G protein.
• Activated α subunit links with adenylyl
cyclase in the membrane.
• Activated adenylyl cyclase converts
intracellular ATP to cyclic AMP.
• Cyclic AMP activates protein kinase A.
• Protein kinase A phosphorylates intracellular
proteins, leading to the cellular response.
Action mechanism
of hydrophilic
hormones via
activation of cyclic
AMP second-
messenger
pathway
3.4 Intercellular Communication
and Signal Transduction cont’d
• Diacylglycerol-inositol triphosphate-
Ca2+ second-messenger pathway
• Binding of hormone (first messenger)
to its receptor activates a G protein.
• Activated α subunit activates
phospholipase C on inner surface of
membrane.
• Activated phospholipase C converts
phosphatidylinositol bisphosphate
(PIP2) to diacylglycerol (DAG) and
inositol trisphosphate (IP3).
Action
mechanism
of hydrophilic
hormones
via
concurrent
activation of
the IP3/Ca2+
second-
messenger
pathway and
the DAG
pathway.
3.4 Intercellular Communication
and Signal Transduction cont’d
• Second messenger systems
• Shared by many cell types
• Multiple steps lead to amplification of
initial signal.
• Amplification by Second-Messenger
Pathway
• Through amplification, very low
concentrations of extracellular
chemical messengers, such as
hormones can trigger pronounced cell
responses.
 Amplification of the initial signal
by a second-messenger pathway
3.4 Intercellular Communication
and Signal Transduction cont’d
• Second messenger systems
• Receptors are subject to regulation
• Downregulation or upregulation of receptor
number
• An example of downregulation: number of
receptors for insulin decreases in response to
chronic elevation of insulin
• Drugs and toxins alter communication
pathways
• Antagonists block a step in the pathway; e.g.,
antihistamine
• Agonists activate a step in the pathway; e.g.,
nicotine
3.5 Membrane Potential
• Membrane potential
• Na+ -
and Cl are major
osmolytes in the extracellular
fluid (ECF).
• K+ is the dominant inorganic
osmolyte in the intracellular
fluid (ICF).
• Osmolyte – solutes involved
in regulating osmotic pressure
3.5 Membrane Potential cont’d
• Membrane potential is the separation of
charges across the plasma membrane.
• Separated charges have the potential to do work.
• Measured in millivolts (mV)
• Attractive force causes separated positive and
negative charges to accumulate along the inner
and outer surfaces of the membrane.
• All living cells have a membrane potential with
excess of negative charges on the inside.
• Cells of excitable tissues (nerve and muscle) have
the ability to produce rapid, transient changes in
membrane potential.
 Membrane has no potential
(equal number of positive and negative charges).
Membrane has potential.
 Separated charges responsible for potential:
The attractive force between these separated charges
causes them to accumulate in a thin layer along the
outer and inner surfaces of the plasma membrane.
3.5 Membrane Potential cont’d
• Resting membrane potential is primarily
due to differences in the distribution and
permeability of key ions.
• Na+ is greater in ECF; K+ is greater in ICF.
• Concentration differences are maintained
by
• Na+-K+ pump
• Different solubilities in cell water and affinity
for cell proteins
• Large, negatively charged (anionic)
proteins (A-) are concentrated in ICF.
3.5 Membrane Potential cont’d
• Na+-K+ pump transports
three Na+ out for every two
K+ in.
• Membrane has more K+ leak
channels than Na+ leak
channels.
• Membrane is 25-30 times
more permeable to K+ than to
Na+.
3.5 Membrane Potential cont’d
• Equilibrium potential
• The equilibrium potential of an ion is the
membrane potential at which there is no
net movement of the ion across the
membrane.
• Concentration gradient is balanced by
opposing electrical gradient.
• Nernst equation for equilibrium potential of an
ion (Eion):
RT [X]o
EX = ln
zF [X]i
Equilibrium potential for K +

EK+ = -90 mV
Typical equilibrium potential for Na+
ENa+ = +60mV
3.5 Membrane Potential cont’d
• Equilibrium potential
• EK = -90 mV
• ENa = +61 mV
• The greater the permeability of the
plasma membrane for a given ion, the
greater the tendency for that ion to
drive the membrane potential toward
the ion’s own equilibrium potential.
• The membrane is more permeable to
K+ than to Na+, so membrane
potential is closer to the K+
equilibrium potential.
Resting membrane potential = -70mV.
 Counterbalance between passive Na +
and K+ leaks and the active Na + /K + pump.