Lec 16: Membrane Structure and transport Flashcards
Important features of the cell membrane
5nm thick
Proteins embedded in it facilitate the exchange of proteins and waste products
Other proteins can act as sensors or receptors that allow the cell to respond to the environment in the appropriate way
Impermeable to most water-soluble molecules
Mechanical properties:
- grows with the cell
- can deform without tearing
- quickly reseals if pierced
amphipathic
a molelcule that has both hydrophilic and hydrophobic parts
movement of individual molecules in the membrane
They can freely move about and round each other and change places, which makes the membrane act somewhat as a two dimensional liquid
This allows for proteins embedded in the membrane to diffuse rapidly around the membrane and interact with each other, which is important for signalling
Allows proteins to move from where they were formed, to all around the cell surface
Ensures even splits of proteins during meiosis
Allows membranes to fuse together a mix their proteins
How are cell membranes assembled?
New phospolipids are manufactured by enzymes attached to the endoplasmic reticulum
They are added to the inside layer of the membrane (the cytosolic side), then randomly flipped to the other orientation by scramblase, a transporter protein to ensure that both sides grow evenly
Asymmetry of cell membranes
Most cell membranes are asymetric in that certain types of phospholipid are only on the cytosolic side, and others are only on the other side. This helps with the directionality of proteins
This is accomplished by flippases
B: it represents the phosphate group, which is always negatively charged
All of the carbohydrates in the plasma membrane face the cell exterior. Which direction do the carbohydrates on internal cell membranes face?
the lumen of the vesicle or organelle: there is the cytosolic and non-cytosolic side.
How do polypeptide chains cross the lipid bilayer?
Typically as an alpha helix: the amino acids in this region usually have hydrophobic side chains, while the polypeptide backbone is hydrophilic, so it will usually form hydrogen bonds with itself, making a helix
Multiple amphipathic alpha helixes will cross the lipid billayer to form a small channel that small hydrophilic molecules can diffuse through
Beta folds can also form into a beta barrel, which also creates a channel through the cell
What helps reinforce the plasma membrane?
In plants, yeasts, and bacteria, the membrane is reinforced by a rigid cell wall (a fibrous layer of proteins, sugars, and other macromolecules that encases the plasma membrane
In animal cells, it’s stabilized by a meshwork of filamentous proteins called the cell cortex that is attached to the underside of the membrane
Membrane domains
some proteins need to be confined to a certain area of the membrane (ie the cells that line the gut need certain proteins only on the side that faces the gut). So some cells will confine certain proteins to localized areas within the bilayer. This is accomplished by proteins that forma continuous junction with neighboring cells, called a tight junction, that don’t let other molecules past them in the cell membrane.
Glycocalyx
protective layer of carbohydrates on the outside surface of the plasma membrane formed by the sugar residues of membrane glycoproteins, proteoglycans, and glycolipids
It helps protect the cell from mechanical damage
Cells can use distinctive features in the glycocalyx to recognize each other
If the backbone of a polypeptide is hydrophilic, how can a transmembrane alpha helix span the hydrophobic portion of the lipid bilayer?
The hydrophobic amino acid side chains in a transmembrane alpha helix interact with the hydrophobic portion of the lipid bilayer
In a patch of animal cell membrane about 10um2 in area, which will be true?
There will be more lipids than proteins. Proteins make up about half the mass of the lipid bilayer, but not half the molecules
When scientists were first studying the fluidity of cell membranes, they did an experiment in which they created hybrid cells. Certain member proteins in a human cell and a mouse cell were labelled using antibodies coupled with different fluorescent tags. The two cells were then coaxed into fusing, resulting the the formation of a single, double-sized hybrid cell. Using fluorescence microscopy, the scientists then tracked the distrubution of the labelled proteins in the hybrid cell.
What best describes the results they saw?
Initially the proteins were confined to their own sides, but over time they mixed and distributed evenly. This suggests that proteins can move freely through the cell surface.
What molecules can naturally diffuse across the lipid bilayer?
CO2, O2, etc (small, non polar molecules)
Two main classes of membrane proteins
transporters: shift small organic molecules or inorganic ions from one side of the membrane to the other by changing shape. Transporters are highly specific, just like enzymes are.
Channels: for tiny hydrophilic pores across the membrane through which substances can pass by diffusion. Most channels only permit the passages of ions, and are called ion channels. Channels discriminate mainly on the basis of size and electric charge.
Passive transport
The spontaneous movement of a solute down its concentration gradient across a cell membrane via a transport protein, such as a channel or a transporter. Doesn’t require energy, just a concentration gradient and the appropriate channel or transporter
Active transport:
The movement of a solute across a membrane against its electrochemical gradient; requires an input of energy, such as that provided by ATP hydrolysis. Carried out by special types of transporters called pumps
something has to pay for the transport. Can be done by:
1) a gradient-driven pump (symport)
2) ATP-driven pump
3) light-driven pump
Concentration gradient/membrane potential
For an uncharged molecule, only the relative concentrations on either side of the membrane (concentration gradient) matter for passive transport.
For charged molecules the concentration gradient and the relative charges on either side of the membrane matter. Most cells maintain a negative potential on the cytosolic side of the membrane.
Electrochemical gradient
the driving force that determines which way an ion will move across a membrane in passive transport. Consists of the combined influence of the ions concentration gradient and its membrane potential
Aquaporins
channel that facilitates the transport of water, but not ions, across cell membranes.
Osmosis
passive movement of water from a region where the concentration of water is high (because the concentration of solutes is low) to a region where the concentration of water is low (because the concentration of solutes is high).
The concentration of solutes inside the cell is usually higher, so unchecked osmosis can cause the cell to swell. Different cells deal with this in different ways
Which type of membrane transport protein can perform both active and passive transport?
Transporters
When glucose moves across a phospholipid bilayer by passive transport, which factor determines the direction of its transport?
The concentrations of glucose on either side of the membrane
What is true about K+ and Na+?
Na+ is the most plentiful positively charged ion outside the cell, while K+ is the most plentiful inside. Cells expend a great deal of energy to maintain this chemical balance
Pump
a transporter that uses a source of energy, such as ATP hydrolysis or sunlight, to actively move a solute across a membrane against its electrochemical gradient
gradient pumps link the active transport of one solute across a membrane to the downhill transport of another. (ex the Na+ gradient can be used to drive a pump that moves another molecule against its gradient
ATP driven pumps use ATP
light-driven pumps use light (and are found mainly in bacteria cells)
Symport
a transporter that transfers two different solutes across a cell membrane in the same direction (ie Na+ driving glucose pump across the cell membrane)
antiport
type of coupled transporter that transfers two different ions or small molecules across a membrane in opposite directions
The epithelial cells that line the gut have glucose-Na+ symport proteins that actively take up glucose from the lumen of the gut after a meal, creating a high glucose concentration in the cytosol. How do these cells release that glucose for use by other tissues in the body?
The cells have glucose uniports in their cell membranes (passive transport because there is a concentration gradient built up in the cell)
When the glucose-Na+ symport protein is in its outward-open state, which is more likely to occur?
Na+ binds to its binding site (higher concentration). It then has to wait for the rare glucose molecule to bind as well, allowing the transport to happen.
channel
a protein that forms a small hydrophilic pore across the membrane, through which selected small molecules or ions can passively diffuse
ion channels
ion-selective (based on diameter and shape). They are transport proteins that form a pore across a lipid bilayer through which specific inorganic ions can diffuse down their electrochemical gradients.
They are also gated: they are not continuously open. They open only briefly and then close again, triggered by a specific stimulus.
No conformation change is needed for each ion to pass through, so its much faster than transporters. They can cause a rapid change of membrane potential in a cell
resting membrane potential
votalge difference across the plasma membrane when the cell is not stimulated.
the cells typically actively transport Na+ outside the cell, and K+ in, but there is usually an open K+ channel, so Na+ build up outisde the cell, and k+ balances, creating a net positive change outside the cell.
changes in membrane potential are one of the most important signaling systems between cells
To pass through the pore of an ion channel, what must be true of an ion?
It must interact with the polar groups in the narrowest part of the channel
For voltage-gated channels, a change in the membrane potential has what effect on the channel?
It alters the probability that the channel will be found in its open conformation
neuron
an electrically excitable cell that integrates and transports information as part of the nervous system; a nerve cell
axon: long extension that conducts electrical signals away from a nerve cell body towards remote target cells
dendrites: short branching structure that extends from the surface of a nerve cell and receives signals from the other neurons
action potential
traveling wave of electrical excitation caused by rapid, transient, self-propagation depolarization of the plasma membrane in a neuron or other excitable cell; also called a nerve impulse
how action potentials work
when a plasma membrane becomes stimulated, it opens it Na+ channels in a wave that travels down the cell’s axon, which causes the Na+ to rapidly diffuse down its electrochemical gradient, changing the membrane potential from about -60mV to about 40mV. Then the Na+ channels close (transiently, then for real).
In response to this change, the K+ channels open, letting them flow out of the cell, down their electrochemical gradient, bringing the membrane back to its resting potential.
Once the action has passed, the Na+ pumps get to work to restore the Na+ and K+ ion gradients to their normal levels
The channels have a transient resting state after opening, called the inactive state. They are closed to ion passage in this state, but this is different from the “closed” state because the closed state means they can react to stimulus. This temporarily keeps it from responding to the action potential again, and back-propagating.
synapses
specialized junction where a nerve cell communicates with another cell (nerve, muscle, gland) usually via a neurotransmitter.
neurotransmitter
small signaling molecule secreted by a nerve cell ant a synapse to transmit information to a post synaptic cell. Examples include acetylcholine, glutamate, GABA, and glycine
can be excitatory or inhibitory
synaptic cleft
the narrow gap between a nerve cell and the cell receiving the signal.
Neurotransmitters cross the synaptic cleft, cause an action in the other cell (if they reach a certain threshold), and are then pumped back in to the cell, or destroyed by enzymes
This is where electrical signals are converted to chemical signals
The depolarization of the nerve-terminal plasma membrane triggers the secretion of neurotransmitters by opening which of the following?
voltage-gated Ca2+ channels in the plasma membrane
When transmitter-gated ion channels in the membrane of a postsynaptic cell open in response to neurotransmitter binding, what happens?
The channels alter the ion permeability of the postsynaptic membrane, which in turn may depolarize the post synaptic membrane.
They open transiently in response to the binding of the neurotransmitter, changing the ion permeability, which causes a change in the membrane potential, and encourages another action potential.
Explain the orientation of membranes in the cell
The cytosolic layer always faces the cytosol, the other layer faces either the outside of the cell, or the inside of a compartment
Which organelles have a double layer?
the mitochondria, the nucleus, and the chloroplasts
What are the basic functions of the plasma membrane?
big role is the fundamental definition of the cell: separating inside from outside. Without that, there would be no living things
communication
import and export
cell growth and motility (flexibility)
What are the three major membrane lipids?
What is different about cholesterol?
It is shorter and has a more rigid membrane structure
How to lipid bilayers form into sealed compartments?
It naturally tries to minimize interactions between water and the fatty acid tails
membrane fluidity: how it happens, what it results in
liposome
How to get things into a cell is one of the most important questions as a biomedical engineer. We rely on liposomes to help deliver them. Dehydrated lipids and the drug are mixed together, then with water, which should form little liposome capsules around the drug. They can be sorted by size using microfluidics. Proteins in the membranes help them fuse with the liposome
water likes each other, but nobody likes lipids, which is why the lipid molecules come together.
If it was the other way around, the membrane would be significantly less fluid
Why is the asymmetry of the lipid bilayer important?
While the membranes are very fluid, it is rare for the phospholipids to flip spontaneously–it takes energy
hybridoma
fuse a b-cell to a cancer cell, and the cancer cell will drive proliferation and the b-cell parts will keep spitting out the antibodies you want
it can only move around fluidly within its layer. The two layers don’t mix except on rare occasions
membrane proteins
- carry out most of the membrane’s functions
- can constitute up to 50% of the mass of plasma membranes
- determine the membrane’s mechanical properties
- provide structural integrity
What are the functions of membrane proteins?
transporters/channels: let things in and out
anchors: provide support and structure (i.e. so your skin doesn’t fall apart when you pinch it)
receptors: transmits a signal (changes conformation in response to a molecule that can’t pass through)
enzymes: like receptors, but catalyze a reaction
Explain why the polypeptide chain of most transmembrane proteins crosses the lipid bilayer as an alpha helix or beta barrel
It has amino acid sequences that can expose hydrophobic side chains on the outside of the structure
What are some mechanisms to restrict the distribution of membrane proteins?
tight junctions:
they also don’t allow anything to sneak in between the cells
active vs passive transport
passive transport moves solutes down and electrochemical gradient
active transport moves solutes against the electrochemical gradient
Na+/K+ pumps
How do cells that line the gut take up glucose and supply it to the other side?
Na+ gradient supplies the energy to bring glucose in (against it’s gradient).
The Na+ then gets pumped back out
Glucose can be passively transported out the other side of the cell because it is at a high concentration in the cell
S(out) + T -> TS -> S(in) + T
A channel doesn’t really bind to solute and thus doesn’t have an intermediate state.
Ways to gate an ion channel
How can ion channels be selectively gated?
They can have just teh right diameter to make the correct bonds to both break the hydrogen bond between water and the ion, and the right diameter to allow the ion to pass through. Just a slightly different size and all the forces won’t balance appropriately. Some of the wrong ones will still get through, this is all just probability
Nothing will happen: acetylcholine only binds to the extracellular side, not the cytosolic side
