biological membranes - genetics and bioengineering · however, there were 2 problems 1....
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Biological membranes
Life at the Edge
The plasma membrane
Is the boundary that separates the living cell from its nonliving
surroundings
About 8 nm thick
Controls traffic into and out of the cell
The plasma membrane exhibits selective permeability
It allows some substances to cross it more easily than others
Figure 7.1
Transport Across Membranes:
Overcoming the Permeability Barrier
•Overcoming the permeability barrier of cell membranes is
crucial to proper functioning of the cell.
•Specific molecules and ions need to be selectively moved
into and out of the cell or organelle .
•Membranes are selectively permeable.
Definitions
•Solution – mixture of dissolved molecules in a liquid
•Solute – the substance that is dissolved
•Solvent – the liquid
Ion Concentrations
•The maintenance of solutes on both sides of the membrane is critical to the cell
–Helps to keep the cell from rupturing
•Concentration of ions on either side varies widely
–Na+ and Cl- are higher outside the cell
–K+ is higher inside the cell
–Must balance the number of positive and negative charges, both inside and outside cell
•Ions and hydrophilic
molecules cannot easily
pass trough the
hydrophobic membrane
•Small and hydrophobic
molecules can
•Must know the list to the
left
Cells and Transport Processes
Cells and cellular compartments - accumulate a variety of
substances
concentrations -very different from those of the surroundings
substances that move across membranes - dissolved gases,
ions, and small organic molecules; solutes
Transport is central to cell function
A central aspect of cell function - selective transport
movement of ions or small organic molecules (metabolites)
Cellular membranes are fluid mosaics of lipids and
proteins
Phospholipids
Are the most abundant lipid in the plasma membrane
Are amphipathic, containing both hydrophobic and hydrophilic regions
For those who forgot…
HYDROPHOBIC SUBSTANCE cannot be dissolved in water
because they do not have affinity to water. Example is oil
HYDROPHILIC SUBSTANCE can be dissolved in water because
they have affinity to it.
How are phospholipids and proteins arranged in the
membranes of the cell?
• The fluid mosaic model of membrane structure
– States that a membrane is a fluid structure with a “mosaic”
of various proteins embedded in it
– Or attached to a double layer of phospholipids
Membrane Models: Scientific Inquiry
Membranes have been chemically analyzed
And found to be composed of proteins and lipids
Scientists studying the plasma membrane
Reasoned that it must be a phospholipid bilayer
This bilayer of molecules exists as stable boundary between two
aqueous compartments
Hydrophilic
head Hydrophobic
tail
WATER
WATER
The Davson-Danielli sandwich model of membrane structure
Stated that the membrane was made up of a phospholipid bilayer
sandwiched between two protein layers
Was supported by electron microscope pictures of membranes
However, there were 2 problems
1. generalization that all membranes of the cell are identical was
challenged
Plasma membrane is 7/8 nm thick and has three layered structure, and inner
mitochondrial membrane is 6 nm thick and looks like a row of beads
2. placement of the proteins since membrane proteins are not very
soluble in water
Membrane proteins have hydrophobic and hydrophilic regions.
If placed on the surface, hydrophobic parts would be in an aqueous environment…
In 1972, Singer and Nicolson
Proposed that membrane proteins are dispersed and individually
inserted into the phospholipid bilayer
Only their hydrophilic regions protrude far enough from the bilayer to
be exposed to water
According to this, the membrane is a mosaic of protein molecules
bobbing in a fluid bilayer of phospholipids
Phospholipid
bilayer
Hydrophilic region
of protein
Hydrophobic region of protein
The Fluidity of Membranes
Membranes are not static sheets of molecules !
Held together by hydrophobic interactions which are weaker than
covalent bonds
Most of the lipids and some of the proteins can drift about laterally
That is in the plane of the membrane
Movement is rapid
However, proteins are larger than lipids and they move slower
The Fluidity of Membranes
Membrane remains fluid as temperature decreases
Phospholipids settle into closely packed arrangement and the membrane
solidifies
The solidification temperature depends on the types of lipids it is made of
The membrane remains fluid at lower temperatures if it is rich in
phospholipids with unsaturated hydrocarbon tails
Those hydrocarbons have kinks in the tails where the double bonds are
located so they cannot pack closely as saturated hydrocarbons
The type of hydrocarbon tails in phospholipids
Affects the fluidity of the plasma membrane
Fluid Viscous
Unsaturated hydrocarbon
tails with kinks Saturated hydro-
Carbon tails
(b) Membrane fluidity
The Fluidity of Membranes
Phospholipids in the plasma membrane
Can move within the bilayer
Lateral movement
(~107 times per second) Flip-flop
(~ once per month)
(a) Movement of phospholipids
Lateral movement
Within the same membrane surface
Fast process
Flip-flop
Or transverse diffusion
From one membrane surface to another
Slow process
The Fluidity of Membranes
The membranes must be fluid to work properly
Fluid as salad oil
When solid it changes its permeability and enzymatic proteins in
the membrane become inactive
Solutes Cross Membranes
Simple Diffusion, Facilitated Diffusion, and Active
Transport
•Three quite different mechanisms are involved in moving
solutes across membranes
•A few molecules cross membranes by simple diffusion, the
direct unaided movement dictated by differences in
concentration of the solute on the two sides of the membrane
•However, most solutes cannot cross the membrane this way
The Role of Membrane Carbohydrates in
Cell-Cell Recognition
Cell-cell recognition
Is a cell’s ability to distinguish one type of neighboring cell from
another
Important for organisms functioning
Basis for the rejection of foreign cells by immune system
The way cells recognize other cells is by binding to surface
molecules
Usually carbohydrates
Membrane carbohydrates Interact with the surface molecules of other cells, facilitating cell-cell recognition
Usually short
Some are covalently bonded to lipids forming molecules called glycolipids
Most of them are bonded to proteins forming glycoproteins
Synthesis and Sidedness of
Membranes
Membranes have distinct inside and outside faces
This affects the movement of proteins synthesized in the
endomembrane system
Membrane proteins and lipids
ER
Transmembrane
glycoproteins
Secretory
protein
Glycolipid
Golgi
apparatus
Vesicle
Transmembrane
glycoprotein
Membrane glycolipid
Plasma membrane:
Cytoplasmic face
Extracellular face
Secreted
protein
4
1
2
3
•Synthesis of membrane proteins and
lipids in the ER. Carbohydrates are
added to the proteins making them
glycoproteins
•Inside Golgi they undergo
carbohydrate modifications becoming
glycolipids
•Proteins are transported in vesicles to
the plasma membrane
•The vesicles fuse with the membrane
releasing secretory proteins form the
cell
Membrane structure results in selective permeability
A cell must exchange materials with its surroundings, a process
controlled by the plasma membrane
A steady traffic of small molecules and ions moves across the
membrane in both directions
Sugars, amino acids and other nutrients enter the cell while waste
products leave the cell
The cell takes in oxygen for cellular respiration and expels CO2
It also regulates concentration of inorganic ions
The Permeability of the Lipid Bilayer
Hydrophobic molecules
Are lipid soluble and can pass through the membrane rapidly
Examples are oxygen, hydrocarbons and CO2
Polar molecules
Do not cross the membrane rapidly
Examples are glucose and other sugars, water
Charged atom or molecule and its surrounding shell of water penetrate
the membrane even more difficult
Transport Proteins
Transport proteins
Allow passage of hydrophilic substances across the membrane
Some of them act as channel proteins where they have hydrophilic
channel that certain molecules use as a tunnel
Others act as carrier proteins which hold onto their passengers and
change shape in a way that shuttles them across the membrane
In both cases the transport protein is specific for the substance it
translocates
Active transport
In other cases, transport proteins move solutes against the
concentration gradient; this is called active transport.
Active transport requires energy such as that released by the
hydrolysis of ATP or by the simultaneous transport of
another solute down an energy gradient.
Concentration gradient or
Electrochemical Potential
The movement of a molecule that has no net charge is
determined by its concentration gradient
Simple or facilitated diffusion involve exergonic movement
“down” the concentration gradient (negative ΔG)
Active transport involves endergonic movement “up” the
concentration gradient (positive ΔG)
The electrochemical potential
The movement of an ion is determined by its
electrochemical potential
the combined effect of its concentration gradient and the
charge gradient across the membrane
The active transport of ions across a membrane creates a
charge gradient or membrane potential (Vm)
Active transport of ions
Most cells have an excess of negatively charged solutes inside
the cell
This charge difference favors the inward movement of cations
such as Na+ and outward movement of anions such as Cl–
In all organisms, active transport of ions across the plasma
membrane results in asymmetric distribution of ions inside
and outside the cell
Functions of active transport
Active transport couples endergonic transport to an
exergonic process, usually ATP hydrolysis
•Active transport performs three important cellular functions
-Uptake of essential nutrients
-Removal of wastes
-Maintenance of nonequilibrium concentrations of certain ions
Direct active transport
accumulation of solute molecules on one side of the
membrane is coupled directly to an exergonic chemical reaction
This is usually hydrolysis of ATP
•Transport proteins driven by ATP hydrolysis are called
transport ATPases or ATPase pumps
Indirect active transport
Indirect active transport depends on the simultaneous
transport of two solutes.
•Favorable movement of one solute down its gradient - drives the
unfavorable movement of the other up its gradient.
•symport or an antiport, depending on whether the two
molecules are transported in the same or different directions.
Direct Active Transport Depends on Four Types of Transport
ATPases
Four types of transport ATPases have been identified
-P-type
-V-type
-F-type
-ABC-type
•They differ in structure, mechanism, location, and roles
P-type ATPases
members of a large family
reversibly phosphorylated by ATP on a specific aspartic acid
residue
8-10 transmembrane segments in a single polypeptide
crosses the membrane multiple times
5 subfamilies (P1-P5)
V-type ATPases
pump protons into organelles
vacuoles, vesicles, lysosomes, endosomes, and the Golgi
complex
two multisubunit components:
integral component embedded in the membrane
peripheral component that juts out from the membrane
surface
F-type ATPases
found in bacteria, mitochondria and chloroplasts
They transport protons and have two components:
–a transmembrane pore (Fo) and
–a peripheral membrane component (F1) that contains the ATP
binding site.
•Both are multisubunit components
ABC-type ATPases
(ATP binding cassette) transporters
cassette describes the catalytic domain that binds ATP as part
of the transport process
comprise a very large family of transport proteins found in
all organisms
Medical significance of ABC-type
ATPases
some of them pump antibiotics or drugs out of cells,
rendering the cell resistant to the drug
Some human tumors are resistant to drugs that normally
inhibit growth of tumors
resistant cells have high concentrations of an ABC transporter
called MDR (multidrug resistance) transport protein
MDR transport protein
pumps hydrophobic drugs out of cells
reducing the cytoplasmic concentration and hence their
effectiveness
transports a wide range of chemically dissimilar drugs
Indirect Active Transport Is Driven by
Ion Gradients
not powered by ATP hydrolysis
inward transport of molecules up their electrochemical
gradients - coupled to and driven by simultaneous inward
movement of Na+ (animals) or protons (plant, fungi,
bacteria) down their gradients
Summary
Structure of plasma membrane
Transport across the membrane
Fluid mosaic model
Fluidity
Crossing membranes
Active transport
Transport ATPases
Simple Diffusion
Unassisted Movement Down the Gradient
movement of a solute from high to lower concentration
only possible for gases, nonpolar molecules, or small polar
molecules
Oxygen and the function of
erythrocytes
Oxygen gas transfers the lipid bilayer readily by simple
diffusion
Erythrocytes take up oxygen in the lungs, where oxygen
concentration is high
release it in the body tissues, where oxygen concentration is
low
Diffusion Always Moves Solutes Toward
Equilibrium
tends to create a random solution in which the concentration
is the same everywhere
Solutes will move toward regions of lower
concentration until the concentrations are equal
Thus diffusion is always movement toward equilibrium !!!!
Osmosis
Diffusion of Water Across a Selectively Permeable
Membrane
Water molecules are polar and so are not affected by the
membrane potential
Water concentration is not appreciably different on opposite
sides of a membrane
Osmosis
If two solutions are separated by a selectively permeable
membrane, permeable to the water but not the solutes, the water will
move toward the region of higher solute concentration.
Osmosis
For most cells, water tends to move inward
Water Balance of Cells Without Walls
Tonicity
Is the ability of a solution to cause a cell to gain or lose water
Has a great impact on cells without walls
Depends in part on its concentration of solutes that cannot cross the
membrane relative to that in the cell itself.
If a solution is isotonic
The concentration of solutes is the same as it is inside the cell
There will be no net movement of water
Isotonic solution
H2O H2O
Normal
Animal cell. An
animal cell fares best
in an isotonic environ-
ment unless it has
special adaptations to
offset the osmotic
uptake or loss of
water.
If a solution is hypertonic
The concentration of solutes is greater than it is inside the cell
The cell will lose water
Hypertonic solution
H2O
Shriveled
If a solution is hypotonic
The concentration of solutes is less than it is inside the cell
The cell will gain water
Hypotonic solution
H2O
Lysed
A cell without rigid walls can tolerate neither excessive uptake or
excessive loss of water
This is automatically solved if a cell lives in isotonic surrounding
Animals and other organisms without rigid cell walls living in
hypertonic or hypotonic environment must have special adaptations
for osmoregulation
Control of water balance
Water Balance of Cells with Walls
Cell walls
Help maintain water balance
Example: plant cell
This cell swells as water enters by osmosis
The elastic wall will expand only so much before it exters back
pressure on the cell that opposes further water uptake
At this point, the cell is turgid
If a plant cell is turgid
It is in a hypotonic environment
It is very firm, a healthy state in most plants
Plant cell. Plant cells
are turgid (firm) and
generally healthiest in
a hypotonic environ-
ment, where the
uptake of water is
eventually balanced
by the elastic wall
pushing back on the
cell.
H2O
Turgid (normal)
If a plant cell is flaccid
It is in an isotonic or hypertonic environment
There is not tendency for water to enter
H2O H2O
Flaccid
A wall is of no advantage if the cell is immersed in hypertonic
environment
Plant cell will lose water to its surroundings and shrink
Plasma membrane pulls away from the wall
Plasmolysis
Causing plant to wilt and can be lethal
Plasmolyzed
H2O
Solute Size
lipid bilayers are more permeable to small molecules
without a transporter even these small molecules move more
slowly than in the absence of a membrane
Solute Polarity
Lipid bilayers are more permeable to nonpolar substances than to polar ones
Nonpolar substances dissolve readily into the hydrophobic region of the bilayer
Large nonpolar molecules such as estrogen and testosterone cross membranes easily, despite their large size
Polarity of a solute can be measured by the ratio of its solubility in an organic solvent to its solubility in water
This is called the partition coefficient
In general, the more nonpolar (hydrophobic) a substance is, the higher the partition coefficient is.
Solute Charge and relevance to cell function
The relative impermeability of polar substances, especially ions, is due to their association with water molecules
The molecules of water form a shell of hydration around polar substances
In order for these substances to move into a membrane, the water molecules must be removed, which requires energy
Every cell must maintain an electrochemical potential across its plasma membrane in order to function.
In most cases this potential is a gradient of either sodium ions (animal cells) or protons (other cells).
Membranes must still be able to allow ions to cross the bilayer in a controlled manner.
Facilitated Diffusion
Protein-Mediated Movement Down the Gradient
In facilitated diffusion
Transport proteins speed the movement of molecules across the
plasma membrane
Most transport proteins are very specific
They transport only particular substances but not others
Transport proteins
•Transport proteins assist most solute across membranes.
•These integral membrane proteins recognize the substances
to be transported with great specificity.
•Some move solutes to regions of lower concentration; this
facilitated diffusion (or passive transport) uses no energy.
Figure 7.7
Glycoprotein
Carbohydrate
Microfilaments
of cytoskeleton Cholesterol Peripheral
protein Integral
protein
CYTOPLASMIC SIDE
OF MEMBRANE
EXTRACELLULAR
SIDE OF
MEMBRANE
Glycolipid
Membrane Proteins and Their Functions A membrane
Is a collage of different proteins embedded in the fluid matrix of the
lipid bilayer
Fibers of
extracellular
matrix (ECM)
Membrane Proteins and Their
Functions
Example red blood cells
More than 50 types of proteins have been found in the plasma
membrane of RBC
Phospholipids form the main fabric of the membrane
Proteins determine most of the membrane functions
Different types of cells contain different sets of membrane proteins
Integral proteins
Penetrate the hydrophobic core of the lipid bilayer
Are often transmembrane proteins, completely spanning the
membrane
Usually α helical proteins
EXTRACELLULAR
SIDE N-terminus
C-terminus
a Helix CYTOPLASMIC
SIDE
Peripheral proteins
Are appendages loosely bound to the surface of the membrane
Not embedded in the lipid bilayer
An overview of six major functions of membrane proteins
Figure 7.9
Transport. (left) 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 ssource
to actively pump substances across the membrane.
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.
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.
(a)
(b)
(c)
ATP
Enzymes
Signal
Receptor
Cell-cell recognition. Some glyco-proteins serve as
identification tags that are specifically recognized
by other cells.
Intercellular joining. Membrane proteins of adjacent cells
may hook together in various kinds of junctions, such as
gap junctions or tight junctions (see Figure 6.31).
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 (see Figure 6.29).
(d)
(e)
(f)
Glyco-
protein
Figure 7.9
Channel proteins
Facilitate Diffusion by Forming Hydrophilic Transmembrane Channels
allow specific solutes to cross the membrane directly
There are three types of channels:
ion channels, porins, and aquaporins
EXTRACELLULAR
FLUID
Channel protein Solute
CYTOPLASM
A channel protein (purple) has a channel through which
water molecules or a specific solute can pass.
(a)
Ion Channels
Allow Rapid Passage of Specific Ions
Ion channels - lined with hydrophilic atoms
remarkably selective
most allow passage of just one ion
separate proteins needed to transport Na+, K+, Ca2+, and
Cl–, etc.
Selectivity - based on both binding sites involving amino acid
side chains, and a size filter
Gated channels
Most ion channels are gated, meaning that they open and close in
response to some stimulus
-Voltage-gated channels open and close in response to
changes in membrane potential
-Ligand-gated channels are triggered by the binding of
certain substances to the channel protein
-Mechano-sensitive channels respond to mechanical forces
acting on the membrane
Porins
Transmembrane Proteins That Allow Rapid Passage of Various Solutes
Pores on outer membranes of bacteria, mitochondria and chloroplasts are larger and less specific than ion channels
The pores are formed by multipass transmembrane proteins called porins
The transmembrane segments of porins cross the membrane as β barrels
Aquaporins
Transmembrane Channels That Allow Rapid Passage
of Water
through membranes of erythrocytes and kidney cells in
animals
root cells and vacuolar membranes in plants.
discovered only in 1992
Carrier proteins
Undergo a subtle change in shape that translocates the solute-binding
site across the membrane
Carrier protein Solute
A carrier protein alternates between two conformations, moving a
solute across the membrane as the shape of the protein changes.
The protein can transport the solute in either direction, with the net
movement being down the concentration gradient of the solute.
(b)
Carrier Proteins Are Analogous to Enzymes in Their Specificity and Kinetics
Carrier proteins are analogous to enzymes
-Facilitated diffusion involves binding a substrate, on a specific solute binding site
-The carrier protein and solute form an intermediate
-After conformational change, the “product” is released (the transported solute)
-Carrier proteins are regulated by external factors
Competitive inhibition of carrier
proteins
Competitive inhibition of carrier proteins -in the presence of
molecules or ions that are structurally related to the correct
substrate
Example: transport of glucose by glucose carrier proteins
inhibited by the other monosaccharides that the carrier
accepts (mannose and galactose)
Carrier Proteins Transport Either One or
Two Solutes
When a carrier protein transports a single solute across the
membrane - uniport
A carrier protein that transports a single solute uniporter
When two solutes are transported simultaneously, and their
transport is coupled - coupled transport
Coupled transport
If the two solutes are moved across a membrane in the same
direction - symport (or cotransport)
If the solutes are moved in opposite directions-antiport (or
countertransport)
Transporters that mediate these processes are symporters
and antiporters
Endocytosis/Exocytosis
For substances the cell needs to take in (endo = in)
or expel (exo = out) that are too large for passive or
active transport
Exocytosis
Large molecules that are manufactured in the cell are
released through the cell membrane.
Endocytosis
Two types: phagocytosis (“cellular eating” for solids)
and pinocytosis (“cellular drinking” for fluids)
Receptor mediated Endocytosis – ligands bind to
specific receptors on cell surface
Summary 2
Simple diffusion
Osmosis
Facilitated diffusion
Channel and carrier proteins
Coupled transport
Endocytosis
Exocytosis