Biol 2305
Cell Membrane, Transport, and Communication
Membranes and Cell Transport
o All cells are surrounded by a plasma membrane.
o Cell membranes are composed of a lipid bilayer with globular proteins embedded in the bilayer.
o On the external surface, carbohydrate groups join with lipids to form glycolipids, and with
proteins to form glycoproteins. These function as cell identity markers.
o
o
Fluid Mosaic Model
In 1972, S. Singer and G. Nicolson proposed the Fluid Mosaic Model of membrane structure
Glycoprotein
Extracellular fluid
Glycolipid
Carbohydrate
Cholesterol
Transmembrane
proteins
Peripheral
protein
Cytoplasm
Filaments of
cytoskeleton
1
o
Phospholipid Bilayer
 Mainly 2 layers of phospholipids; the non-polar tails point inward and the polar heads are
on the surface.
 Contains cholesterol in animal cells.
 Is fluid, allowing proteins to move around within the bilayer.
Polar
hydro-philic
heads
Nonpolar
hydro-phobic
tails
Polar
hydro-philic
heads
Phospholipids
 In phospholipids, two of the –OH groups on glycerol are joined to fatty acids. The third –
OH joins to a phosphate group which joins, in turn, to another polar group of atoms.
 The phosphate and polar groups are hydrophilic (polar head) while the hydrocarbon chains
of the 2 fatty acids are hydrophobic (nonpolar tails).
Hydrophobic tails
Hydrophilic head
o
Choline
Phosphate
Glycerol
Fatty acids
Hydrophilic
head
Hydrophobic
tails
Structural formula
Space-filling model
Phospholipid symbol
Membrane Components
o Membrane carbohydrates
o Interact with the surface molecules of other cells, facilitating cell-cell recognition
o Cell-cell recognition is a cell’s ability to distinguish one type of neighboring cell from another
o Steroid Cholesterol
o Wedged between phospholipid molecules in the plasma membrane of animal cells.
o At warm temperatures (such as 37°C), cholesterol restrains the movement of phospholipids
and reduces fluidity.
o At cool temperatures, it maintains fluidity by preventing tight packing.
o Thus, cholesterol acts as a “temperature buffer” for the membrane, resisting changes in
membrane fluidity as temperature changes.
Cholesterol
2
o
Membrane Proteins
 A membrane is a collage of different proteins embedded in the fluid matrix of the lipid
bilayer
 Peripheral proteins are appendages loosely bound to the surface of the membrane
 Integral proteins penetrate the hydrophobic core of the lipid bilayer
 Many are transmembrane proteins, completely spanning the membrane
Fibers of extracellular
matrix (ECM)
EXTRACELLULAR
SIDE
N-terminus
Glycoprotein
Carbohydrate
Glycolipid
Microfilaments
of cytoskeleton Cholesterol
Peripheral
protein
C-terminus
Integral
protein
 Helix
CYTOPLASMIC
SIDE
Functions of Cell Membranes
o Regulate the passage of substance into and out of cells and between cell organelles and cytosol
o Detect chemical messengers arriving at the surface
o Link adjacent cells together by membrane junctions
o Anchor cells to the extracellular matrix
Functions of Plasma Membrane Proteins
Outside
Plasma
membrane
Inside
Transporter
Enzyme
Cell surface identity
marker
Cell adhesion
Cell surface
receptor
Attachment to the
cytoskeleton
3
6 Major Functions of Membrane Proteins
1. Transport - A protein that spans the membrane may provide a hydrophilic channel across the
membrane that is selective for a particular solute. (right) Other transport proteins shuttle a
substance from one side to the other by changing shape. Some of these proteins hydrolyze ATP as
an energy source to actively pump substances across the membrane
2. Enzymatic activity - A protein built into the membrane may be an enzyme with its active site
exposed to substances in the adjacent solution. In some cases, several enzymes in a membrane are
organized as a team that carries out sequential steps of a metabolic pathway.
3. Signal transduction - A membrane protein may have a binding site with a specific shape that
fits the shape of a chemical messenger, such as a hormone. The external messenger (signal) may
cause a conformational change in the protein (receptor) that relays the message to the inside of the
cell.
4. Cell-cell recognition - Some glycoproteins serve as identification tags that are specifically
recognized by other cells.
5. Intercellular joining - Membrane proteins of adjacent cells may hook together in various kinds
of junctions, such as gap junctions or tight junctions
6. Attachment to the cytoskeleton and extracellular matrix (ECM) - Microfilaments or
other elements of the cytoskeleton may be bonded to membrane proteins, a function that helps
maintain cell shape and stabilizes the location of certain membrane proteins. Proteins that adhere
to the ECM can coordinate extracellular and intracellular changes
o
Cell Junctions - Long-lasting or permanent connections between adjacent cells, 3 types of cell
junctions: Tight, anchoring & communicating.
1. Tight Junctions - Connect cells into sheets. Because these junctions form a tight seal
between cells, in order to cross the sheet, substances must pass through the cells, they
cannot pass between the cells.
Tight
junction
2. Anchoring Junctions - Attach the cytoskeleton of a cell to the matrix surrounding the
cell, or to the cytoskeleton of an adjacent cell.
Plasma
membranes
Intracellular
attachment
proteins
Cell
1
Cell
2
Cytoskeletal
filament
Intercellular
space
Transmembrane
linking proteins
Extracellular
matrix
4
3. Communicating (Gap) Junctions - Link the cytoplasms of 2 cells together, permitting
the controlled passage of small molecules or ions between them.
Two adjacent connexons
form a gap junction
Connexon
Adjacent plasma
membranes
Intercellular space
Membrane Transport
o The plasma membrane is the boundary that separates the living cell from its nonliving
surroundings
o In order to survive, A cell must exchange materials with its surroundings, a process controlled by
the plasma membrane
o Materials must enter and leave the cell through the plasma membrane.
o Membrane structure results in selective permeability, it allows some substances to cross it more
easily than others
o
Passive Transport - Passive transport is diffusion of a substance across a membrane with no
energy investment; 4 Types:
1. Simple diffusion
2. Dialysis
3. Osmosis
4. Facilitated diffusion
o Diffusion
o The net movement of a substance from an area of higher concentration to an area


of lower concentration; down a concentration gradient
Caused by the constant random motion of all atoms and molecules
Movement of individual atoms & molecules is random, but each substance moves down its
own concentration gradient.
Solutions and Transport
o Solution – homogeneous mixture of two or more components
1. Solvent – dissolving medium
2. Solutes – components in smaller quantities within a solution
o Intracellular fluid – nucleoplasm and cytosol
o Extracellular fluid
1. Interstitial fluid – fluid on the exterior of the cell within tissues
2. Plasma – fluid component of blood
5
Diffusion
Lump
of sugar
Random movement
leads to net movement
down a concentration
gradient
Water
No net movement at
equilibrium
o
Diffusion Across a Membrane
o The membrane has pores large enough for the molecules to pass through.
o Random movement of the molecules will cause some to pass through the pores; this will
happen more often on the side with more molecules. The dye diffuses from where it is more
concentrated to where it is less concentrated
o This leads to a dynamic equilibrium: The solute molecules continue to cross the
membrane, but at equal rates in both directions.
Net diffusion
Net diffusion
Equilibrium
o Two different solutes are separated by a membrane that is permeable to both
o Each solute diffuses down its own concentration gradient.
o There will be a net diffusion of the purple molecules toward the left, even though the total
solute concentration was initially greater on the left side
Net diffusion
Net diffusion
Net diffusion
Net diffusion
Equilibrium
Equilibrium
6
o
The Permeability of the Lipid Bilayer
o Permeability Factors
 Lipid solubility
 Size
 Charge
 Presence of channels and transporters
o Hydrophobic molecules are lipid soluble and can pass through the membrane rapidly
o Polar molecules do not cross the membrane rapidly
o Transport proteins allow passage of hydrophilic substances across the membrane
Passive Transport Processes
o 3 special types of diffusion that involve movement of materials across a semipermeable membrane
o Dialysis/selective diffusion of solutes
1. Lipid-soluble materials
2. Small molecules that can pass through membrane pores unassisted
o Facilitated diffusion - substances require a protein carrier for passive transport
o Osmosis – simple diffusion of water
Osmosis –
o Diffusion of the solvent across a semipermeable membrane.
o In living systems the solvent is always water, so biologists generally define osmosis as the diffusion
of water across a semipermeable membrane:
7
Lower
concentration
of solute (sugar)
Higher
concentration
of sugar
Same concentration
of sugar
Selectively
permeable membrane: sugar molecules cannot pass
through pores, but
water molecules can
Water molecules
cluster around
sugar molecules
More free water
molecules (higher
concentration)
Fewer free water
molecules (lower
concentration)
Osmosis

Water moves from an area of higher
free water concentration to an area
of lower free water concentration
Osmotic Pressure –
o Osmotic pressure of a solution is the pressure needed to keep it in equilibrium with pure H20.
o The higher the [solutes] in a solution, the higher its osmotic pressure.
o Tonicity is the ability of a solution to cause a cell to gain or lose water – based on the
concentration of solutes
o
Fofi’s Definition of Osmosis
o Osmosis is the diffusion of water across a semipermeable membrane from a
hypotonic solution to a hypertonic solution
o
Tonicity
o If 2 solutions have equal [solutes], they are called isotonic
o If one has a higher [solute], and lower [solvent], is hypertonic
o The one with a lower [solute], and higher [solvent], is hypotonic
Hypotonic solution
H2O
Lysed
Isotonic solution
Hypertonic solution
H2O
H2O
Normal
H2O
Shriveled
8
Facilitated Diffusion –
 Diffusion of solutes through a semipermeable membrane with the help of special transport
proteins i.e. large polar molecules and ions that cannot pass through phospholipid bilayer.
 Two types of transport proteins can help ions and large polar molecules diffuse through cell
membranes:
1. Channel proteins – provide a narrow channel for the substance to pass through.
2. Carrier proteins – physically bind to the substance on one side of membrane and release it
on the other.
Characteristics of Facilitated Diffusion:
 Specific – each channel or carrier transports certain ions or molecules only
 Passive – direction of net movement is always down the concentration gradient
 Saturates – once all transport proteins are in use, rate of diffusion cannot be
increased further
o
Active Transport
1. Uses energy (from ATP) to move a substance against its natural tendency e.g. up a
concentration gradient.
2. Requires the use of carrier proteins (transport proteins that physically bind to the
substance being transported).
 2 types: Membrane pump & Cotransport
 Membrane pump (protein-mediated active transport)
1. A carrier protein uses energy from ATP to move a substance across a
membrane, up its concentration gradient
9

o
Coupled transport (cotransport); 2 stages:
1. Carrier protein uses ATP to move a substance across the membrane against its
concentration gradient. Storing energy.
2. Coupled transport protein allows the substance to move down its
concentration gradient using the stored energy to move a second substance up
its concentration gradient
Sodium-potassium Pump – a key pump in this course – active transport system
[Na+] high
[K+] low
1. Cytoplasmic Na+ binds
to the sodium-potassium
pump.
Na+
Na+
Na+
Na+
low
[K+] high
ATP
[Na+]
CYTOPLASM
K+
2. Na+ binding stimulates
phosphorylation by ATP.
Na+
ADP
Na+
Na+
Na+
6.
is released and
sites are receptive again;
the cycle repeats.
3. Phosphorylation causes the
protein to change its conformation,
expelling Na+ to the outside.
Na+
K+
P
K+
5. Loss of the phosphate
restores the protein’s
original conformation.
K+
4. Extracellular K+ binds to the
protein, triggering release of the
Phosphate group.
K+
K+
K+
Pi
o
Pi
Bulk Transport
o Allows small particles, or groups of molecules to enter or leave a cell without actually passing
through the membrane.
o 2 mechanisms of bulk transport: endocytosis and exocytosis.
10
Endocytosis
o The plasma membrane envelops small particles or fluid, then seals on itself to form a
vesicle or vacuole which enters the cell:
 Phagocytosis: The substance engulfed is a solid particle

Pinocytosis: The substance engulfed is a liquid
Process of Phagocytosis
11
Exocytosis
o The reverse of endocytosis
o During this process, the membrane of a vesicle fuses with the plasma membrane and its
contents are released outside the cell:
Cells Communication
o Direct contact
 Cells touch each other and signal molecules travel through special connections called
communicating junctions
 Communicating Junctions link the cytoplasms of 2 cells together, permitting the controlled
passage of small molecules or ions between them.
Adjacent connexons
form a gap junction
o
o
o
Paracrine signaling
Endocrine signaling
Synaptic signaling
Local and long-distance cell communication in animals
Local signaling
Long-distance signaling
Target cell
Secreting
cell
Electrical signal
along nerve cell
triggers release of
neurotransmitter
Neurotransmitter
diffuses across
synapse
Secretory
vesicle
Local regulator
diffuses through
extracellular fluid
(a) Paracrine signaling. A secreting cell acts
on nearby target cells by discharging
molecules of a local regulator (a growth
factor, for example) into the extracellular
fluid.
Endocrine cell
Target cell
is stimulated
Blood
vessel
Hormone travels
in bloodstream
to target cells
Target
cell
(b) Synaptic signaling. A nerve cell
releases neurotransmitter molecules
into a synapse, stimulating the
target cell.
(c) Hormonal signaling. Specialized
endocrine cells secrete hormones
into body fluids, often the blood.
Hormones may reach virtually all
body cells.
12
Cell Signaling
o The cells of a organism communicate with each other by releasing signal molecules that bind to
receptor proteins located either on or inside of target cells.
EXTRACELLULAR
FLUID
1 Reception
Plasma membrane
CYTOPLASM
2 Transduction
3 Response
Receptor
Activation
of cellular
response
Relay molecules in a signal transduction pathway
Signal
molecule
Three stages of cell signaling:
o Reception - each target cell has receptors that detect a specific signal molecule and binds to it
 A signal molecule binds to a receptor protein, causing it to change shape
 The binding between signal molecule (ligand) and receptor is highly specific
 A conformational change in a receptor
 Often the initial transduction of the signal
Transduction – binding of the signal molecule changes the receptor protein in some way that
initiates transduction or conversion of the signal to a form that can bring about a specific cellular
response
o Response – transduced signal triggers a specific cellular response, any cell activity
o
Cell Receptors
1. Cell surface receptors - Signal molecules that cannot pass through the plasma membrane
bind to receptors located on the surface of the membrane
 Chemical or ligand-gated ion channels
 Enzymatic receptors
 G-protein-linked receptors
2. Intracellular receptors –
 Some signal molecules that are small or hydrophobic can pass through the plasma
membrane and bind to receptors located inside the cell
 Intracellular receptors are cytoplasmic or nuclear proteins
13
o
Intracellular Receptors
1. Gene Regulators –
 Signal molecule joins to the receptor, the receptor changes shape and a DNA binding
site is exposed.
 The DNA binding site joins to a specific segment of DNA and activates (or
suppresses) a particular gene
2. Enzyme Receptor –


These receptors function as enzymes – proteins that catalyze (speed up) specific
chemical reactions.
When a signal molecule joins to the receptor, the receptor’s catalytic domain is
activated (or deactivated).
Steroid hormone interacting with an intracellular receptor
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
The steroid
hormone testosterone
passes through the
plasma membrane.
2 Testosterone binds
to a receptor protein
in the cytoplasm,
activating it.
3 The hormonereceptor complex
enters the nucleus
and binds to specific
genes.
DNA
mRNA
NUCLEUS
1
4 The bound protein
stimulates the
transcription of
the gene into mRNA.
New protein
5 The mRNA is
translated into a
specific protein.
CYTOPLASM
14
Signal Pathways: Membrane Receptors
o
Chemically Gated Ion Channels - Open or close when the signal molecule binds to the
channel. Typically allow ions in or out of the cell.
Gate
Gate
close
Closed
Signal
molecule
(ligand)
Ions
Plasma
Membrane
Ligand-gated
ion channel receptor
Gate open
Cellular
response
Gate close
o
Enzymatic Receptors - Embedded in the plasma membrane, with their catalytic site exposed
inside the cell. Catalytic site activated when the signal molecule joins to the receptor. Function as
protein kinases (enzymes that phosphorylate proteins.)
Signal-binding site
Signal
molecule
 Helix in the
Membrane
Tyr
Tyr
Tyr
Tyrosines
Tyr
Tyr
Tyr
Signal
molecule
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosine
kinase proteins
(inactive monomers)
CYTOPLASM
Tyr
Tyr
Tyr
Dimer
Activated
relay proteins
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
6
ATP
Activated tyrosinekinase regions
(unphosphorylated
dimer)
6 ADP
P Tyr
P Tyr
P Tyr
Tyr P
Tyr P
Tyr P
Fully activated receptor
tyrosine-kinase
(phosphorylated
dimer)
P Tyr
P Tyr
P Tyr
Tyr P
Tyr P
Tyr P
Cellular
response 1
Cellular
response 2
Inactive
relay proteins
15

o
Protein kinases activate other proteins. Creates a cascade-like pathway eventually
leading to a targeted cellular response
G-protein-linked Receptors - Signal molecule joins to a receptor, the receptor activates a G
protein. The activated G protein can then activate an ion channel or enzyme in the plasma
membrane.
Signal-binding site
Segment that
interacts with
G proteins
G-protein-linked
receptor
Plasma Membrane
Activated
receptor
Signal molecule
Inactive
enzyme
GDP
CYTOPLASM
G-protein
(inactive)
Enzyme
GDP
GTP
Activated
enzyme
GTP
GDP
Pi
Cellular response
16
o
Second Messengers –
 Some enzymatic receptors and most G-protein-linked receptors relay their message into the
cell by activating other molecules or ions inside the cell.
 These transducers convert extracellular signals into intracellular messages which create a
response
 These molecules and ions, called second messengers, transmit the message within the
cell.
 The 2 most common second messengers are cAMP and Ca++
o
cAMP Second Messenger - G-protein-signaling pathway
1. Signal molecule binds to surface receptor
2. Surface receptor activates a G protein
3. G protein activates the membrane-bound enzyme, adenylyl cyclase
4. Adenylyl cyclase catalyzes synthesis of cAMP, which binds to a protein kinase
5. Target protein initiates cellular change
First messenger
(signal molecule
such as epinephrine)
G protein
G-protein-linked
receptor
Adenylyl
cyclase
GTP
ATP
Second
cAMP messenger
Protein
kinase A
Cellular responses
17
o
Cyclic AMP - cAMP recycling takes place in the mitochondria as a part of ATP synthesis
NH2
N
N
O
–O
O
O
O
O
O
O
O
P
Pyrophosphate
OH OH
ATP
P Pi
O
HO P O CH2
O
O
N
N
O
Phoshodiesterase
CH2
N
N
N
N
Adenylyl cyclase
P O P O P O Ch2
O
N
N
N
N
NH2
NH2
O
H2O
O
OH
Cyclic AMP
OH OH
AMP
Cyclic AMP Pathway Amplification
o
Calcium and IP3 in signaling pathways
1. Signal molecule binds to surface receptor
2. Surface receptor activates a G protein
3. G protein activates the membrane-bound enzyme, phospholipase C
4. Phospholipase C catalyzes synthesis of inositol triphosphate (IP3), which stimulates release
of Ca++ from ER
5. Released Ca++ initiates cellular change
18
Calcium & IP3 in signaling pathways
1 A signal molecule binds
to a receptor, leading to
activation of phospholipase C.
EXTRACELLULAR
FLUID
Phospholipase C cleaves a
plasma membrane phospholipid
called PIP2 into DAG and IP3.
DAG functions as
a second messenger
in other pathways.
Signal molecule
(first messenger)
G protein
DAG
GTP
PIP2
G-protein-linked
receptor
Phospholipase C
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
Various
proteins
activated
Ca2+
Cellular
responses
Ca2+
(second
messenger)
CYTOSOL
4 IP3 quickly diffuses through
the cytosol and binds to an IP3–
gated calcium channel in the ER
membrane, causing it to open.
5 Calcium ions flow out of
the ER (down their concentration gradient), raising
the Ca2+ level in the cytosol.
6 The calcium ions
activate the next
protein in one or more
signaling pathways.
Signal Pathways: Signal Amplification
o Transducers convert extracellular signals into intracellular messages which create a response
o Signal Amplification - Stimulation of glycogen breakdown in a liver cell by epinephrine
Reception
Binding of epinephrine to G-protein-linked receptor (1 molecule)
Transduction
Inactive G protein
Active G protein (102 molecules)
Inactive adenylyl cyclase
Active adenylyl cyclase (10 2)
ATP
Cyclic AMP (104)
Inactive protein kinase A
Active protein kinase A (10 4)
Inactive phosphorylase kinase
Active phosphorylase kinase (10 5)
Inactive glycogen phosphorylase
Active glycogen phosphorylase (10 6)
Response
Glycogen
Glucose-1-phosphate
(108 molecules)
19
A Phosphorylation Cascade
Signal molecule
Receptor
Activated relay
molecule
Inactive
protein kinase
1
1 A relay molecule
activates protein kinase 1.
ho
sp
ATP
ADP
PP
Inactive
protein kinase
3
e
ad
sc
ca
Pi
3 Active protein kinase 2
then catalyzes the phosphorylation (and activation) of
protein kinase 3.
P
Active
protein
kinase
2
on
ati
ryl
Inactive
protein kinase
2
ATP
ADP
5 Enzymes called protein
phosphatases (PP)
catalyze the removal of
the phosphate groups
from the proteins,
making them inactive
and available for reuse.
o
Ph
2 Active protein kinase 1
transfers a phosphate from ATP
to an inactive molecule of
protein kinase 2, thus activating
this second kinase.
Active
protein
kinase
1
Pi
Active
protein
kinase
3
PP
Inactive
protein
P
4 Finally, active protein
kinase 3 phosphorylates a
protein (pink) that brings
about the cell’s response to
the signal.
ATP
P
ADP
Pi
PP
Active
protein
Cellular
response
20