Shu-Ping Lin, Ph.D.
Institute of Biomedical Engineering E-mail: [email protected]
Website: http://web.nchu.edu.tw/pweb/users/splin/
Cells and Their Housekeeping Functions –
Cell Membrane & Membrane Potential
* Cell membrane, also called plasma membrane, separates cell interior from surroundings
Thin barrier = 7~10 nm thick
Controls traffic in & out of
the cell
Selectively permeable
* Made of phospholipids, proteins, carbohydrates & other macromolecules
*Phospholipids arrange as a bilayer:
Hydrophobic fatty acid tails
Hydrophilic phosphate group head
http://en.wikipedia.org/wiki/Cell_membrane#Lipid_bilayer
Phospholipid Bilayer
polar hydrophilic heads
nonpolar hydrophobic tails
polar hydrophilic heads
http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
Several important functions:
*A. Allow nutrients to enter cell, *B. Keep out unwanted molecules and particles, *C. Transport waste out into extracellular fluid, *D. Prevent needed metabolites and ions from leaving cell
Inherently amphipathic nature: possess both hydrophilic & hydrophobic structures
More Than Lipids…
In 1972, S.J. Singer & G. Nicolson proposed that membrane proteins are inserted into the phospholipid bilayer
It’s like a fluid… It’s like a mosaic… It’s the Fluid Mosaic Model!
http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
Cell membrane is composed of a double layer of phospholipid molecules (called phospholipid or lipid bilayer), protein molecules associated with lipid bilayer, and carbohydrate-containing cell coat called glycocalyx.
Extracellular fluid
Cholesterol
Cytoplasm
Glycolipid
Transmembrane proteins
Filaments of cytoskeleton
Peripheral protein
Glycoprotein
Phospholipids
http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
Membrane Fat Composition Varies
Fat composition affects flexibility
membrane must be fluid & flexible
about as fluid as thick salad oil
% unsaturated fatty acids in phospholipids
keep membrane less viscous
cold-adapted organisms, like winter wheat
increase % in autumn
cholesterol in membrane
http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
Membrane Proteins Proteins determine membrane’s specific functions
Cell membrane & organelle membranes each have unique
collections of proteins
Membrane proteins:
Peripheral proteins
Loosely bound to surface of membrane
Cell surface identity marker (antigens)
Integral proteins
Penetrate lipid bilayer, usually across whole membrane
Transmembrane protein
Transport proteins
channels, pumps
http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
Why are proteins the perfect molecule to build structures in the cell membrane?
http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
Classes of Amino Acids
What do these amino acids have in common?
nonpolar & hydrophobic http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
Classes of Amino Acids What do these amino acids have in common?
polar & hydrophilic I like the polar ones the best!
http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
Proteins Domains Anchor Molecule
Within membrane Nonpolar amino acids
Hydrophobic
Anchors protein into membrane
On outer surfaces of membrane
Polar amino acids
Hydrophilic
Extend into extracellular fluid & into cytosol
Polar areas of protein
Nonpolar areas of protein http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
Many Functions of Membrane Proteins
Outside
Plasma membrane
Inside
Transporter Cell surface receptor
Enzyme activity
Cell surface identity marker
Attachment to the cytoskeleton
Cell adhesion
http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
Membrane Carbohydrates
The carbohydrates are not inserted into the membrane -- they are too hydrophilic for that. They are attached to embedded proteins -- glycoproteins.
Play a key role in cell-cell recognition
Ability of a cell to distinguish one cell from another
Antigens
Important in organ & tissue development
Basis for rejection of foreign cells by immune system
http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
Movement Across the Cell Membrane
http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
What molecules can get through directly?
Small nonpolar molecules such as carbon dioxide, nitrogen, and oxygen diffuse freely across the bilayer.
Lipid bilayer is also permeable to small and uncharged polar molecules such as urea and ethanol.
Other small hydrophobic molecules: fats and other lipids
NOT get through directly? Ions: salts, ammonia (NH3)
Large uncharged or charged polar molecules: starches, proteins
H2O molecule has 2 pathways: Lipid pathway
Water channel-protein pathway (polar molecules)
Selectively Permeable
Diffusion Across Cell Membrane
Cell membrane is the boundary between inside & outside…
Separates cell from its environment
IN food carbohydrates sugars, proteins amino acids lipids salts, O2, H2O
OUT waste ammonia salts CO2
H2O products
cell needs materials in & products or waste out
IN
OUT
Can it be an impenetrable boundary? NO!
http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
Diffusion
2nd Law of Thermodynamics governs biological systems universe tends towards disorder (entropy)
Diffusion
movement from high low concentration
http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
Diffusion Move from HIGH to LOW concentration
“passive transport”
no energy needed
diffusion
osmosis
movement of water
Osmotic pressure: the pressure is required to stop the net flow of water across a membrane separating solutions of different particulate concentration
Zero flux http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
2007-2008
The Special Case of Water: Movement of water across the cell membrane
http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
Osmosis
Osmosis is diffusion of water
Diffusion of water from high concentration of water to low concentration of water
across a semi-permeable membrane
http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
Concentration of Water
Direction of osmosis is determined by comparing total solute concentrations
Hypertonic - more solute, less water
Hypotonic - less solute, more water
Isotonic - equal solute, equal water
hypotonic hypertonic
water
net movement of water
http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
Effect of Osmotic Pressure Suppose an animal or a plant cell is placed in a solution of sugar or salt in
water.
If the medium is hypotonic — a dilute solution, with a higher water concentration than the cell The cell will gain water and wilt through
osmosis.
If the medium is isotonic — a solution with exactly the same water concentration as the cell There will be no net movement of water
across the cell membrane.
If the medium is hypertonic — a concentrated solution, with a lower water concentration than the cell The cell will lose water and shrink by osmosis.
http://en.wikipedia.org/wiki/Osmosis
freshwater balanced saltwater
Managing Water Balance Cell survival depends on balancing water uptake & loss
Animal cells culture: must maintain in isotonic cell culture medium (concentration of solutes is close to cell cytoplasm)
http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
Aquaporins Cores of these channel proteins are hydrophilic
Water moves rapidly into & out of cells
Multiple water molecules pass through membrane at a rate of 108 molecules/sec
Evidence that there were water channels
1991 | 2003
Peter Agre John Hopkins
Roderick MacKinnon Rockefeller
http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
Channels Through Cell Membrane
Membrane becomes semi-permeable with protein channels
specific channels allow specific material across cell membrane
inside cell
outside cell
sugar aa H2O
salt NH3
http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
Facilitated Diffusion Diffusion through protein channels
Channels move specific molecules across cell membrane
No energy needed
“The Bouncer”
open channel = fast transport
facilitated = with help
high
low
http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
Active Transport
“The Doorman”
conformational change
Cells may need to move molecules against concentration gradient
Shape change transports solute from one side of membrane to other
Protein “pump”
“Costs” energy = ATP
ATP
low
high
http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
Many Models & Mechanisms of Active Transport
Ions and polar molecules across cell membranes include:
ATP-powered pumps
Transporter proteins
Ion channels
The arrows indicate the direction from high to low concentration of the ion or polar molecule across membrane
high
low
low low
high high
Getting through cell membrane
Passive Transport
Simple diffusion diffusion of nonpolar, hydrophobic molecules
lipids
high low concentration gradient
Facilitated transport diffusion of polar, hydrophilic molecules
through a protein channel high low concentration gradient
Active transport
diffusion against concentration gradient low high
uses a protein pump
requires ATP
ATP
Transport Summary
simple diffusion
facilitated diffusion
active transport
ATP
http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg
Active Transport- Na+-K+ Pump Sodium ion binds to transport protein in configuration 1 ATP
molecule associates with transport protein After ATP
hydrolysis, phosphate group is transferred to transport protein Causing to switch of configuration 2 Sodium ion is released to the outside of cell Potassium ion is bound to attachment site of transport protein Binding of potassium ion Result in the release of phosphate group Protein goes back to configuration 1 Potassium ion is released into cell
Cycle is completed with the attachment of sodium ion into cavity of transport protein
Proton pumps, in a lysosomal membrane, are used by plants, bacteria, and fungi to create
electrochemical gradients (sodium-potassium pumps are employed by animals for the same purpose)
www.mansfield.ohio-state.edu/~sabedon/lectures/.../campbl08.ppt
Active Transport- Proton Pump
NH2
H+
COOH
Cytoplasm
Retinal chromophore
Nonpolar (hydrophobic) a-helices in the cell membrane H+
Porin monomer
b-pleated sheets
Bacterial outer membrane
proton pump channel in photosynthetic bacteria
Water channel in bacteria
function through conformational change = shape change
Examples
Membrane Electrical Potential Membrane potential: The electrical charge across a cell membrane; the
difference in electrical potential inside and outside the cell.
Axons have two basic electrical potentials:
1. Resting membrane potential: The membrane potential of a neuron when it is not being altered by excitatory or inhibitory postsynaptic potentials.
2. Action potential: The brief electrical impulse that provides the basis for conduction of information along an axon.
www.psych.yorku.ca/desouza/PSYC3250/M/class2/Lecture2.../Lecture2.ppt
Electrochemical Gradient • An Electrochemical Gradient is a Concentration Gradient with Ions:
- These ions want to move down their concentration gradient
- These ions (particularly) also want to move towards the opposite charge found on the other side of the membrane
- This attraction for the other side of membranes (membrane potential) can be harnessed to do work
- Electrochemical gradients essentially are batteries, i.e., means of physically storing electrical energy
www.mansfield.ohio-state.edu/~sabedon/lectures/.../campbl08.ppt