1
Q
Generalized Cells
A
- All cells have some common structures and functions
- Human cells have three basic parts: Plasma membrane, Cytoplasm, Nucleus
2
Q
Plasma Membrane
A
- Lipid bilayer and proteins in constantly changing fluid mosaic
- Players dynamic role in cellular activity
- Separates intercellular fluid (ICF) from extracellular fluid (ECF)
- Cells surrounded by interstitial fluid (IF)
- Plasma membrane allows cells to:
- obtain from IF exactly what it needs, exactly ehrn it is needed
- keep out what it does not need
3
Q
Membrane Lipids
A
- 75% phospholipids:
- phosphate head: polar and hydrophilic
- fatty acid tails: nonpolar and hydrophobic
- 5% glycolipids: Lipids with polar sugar groups on outer membrane surface
- 20% Cholesterol: increase membrane stability
4
Q
Membrane Proteins
A
- Allow communication with environment
- 1/2 mass of plasma membrane
- Most specialized membrane function
- some float freely
- Some tethered to intracellular structures
two types: Integral proteins, peripheral proteins
5
Q
Integral Proteins
A
- Firmly inserted into membrane
- Have hydrophobic and hydrophilic regions
- function as transport proteins, enzymes, or receptors
6
Q
Peripheral Proteins
A
- loosely attached to integral proteins
- Include filaments on the intracellular surface for membrane support
- Function as enzymes; motor proteins for shape change during cell division and muscle contraction; cell-to-cell connections
7
Q
Six Functions of Membrane Proteins
A
1: Transport
2: Receptors for signal transduction
3: Attachment to the cytoskeleton and extracellular matrix
4: Enzymatic activity
5: Intracellular joining
6: Cell-Cell recognition
8
Q
Types of Membrane Transport
A
- Plasma membranes are selectively permeable: some molecules pass through easily; some do not
- Passive Processes: No cellular Energy(ATP) required, substance moves down its concentration gradient
- Osmosis
- Active Processes: Energy(ATP) required, Occurs only in living cell membranes
9
Q
Passive transport
A
- Diffusion
*Facilitieted transport - Osmosis
10
Q
Diffusion
A
- Describes the spread of particles (which can also be atoms or molecules) through random motion from regions of higher concentration to regions of lower concentration
- Diffusion can still occur when there is no concentration gradient (but there will be no net flux)
- Driven by a decrease in Gibbs free energy
11
Q
Macroscopic theory of diffusion
A
- Fick’s first law of diffusion: Net flux is proportional to the spatial gradient of the concentration function
- Proposed in an analogy to Fourier’s law of heat transfer J = -D(dC/dx) Fick’s first law, where:
- J = Diffusion flux, amount of substance per unit area per unit time
- D = Diffusion coefficient, length/time
- C = Concentration, amount of substance per unit volume
- x = position, length
- Fick’s second law of diffusion: The time rate of change in concentration is proportional to the curvature of the concentration function
- Follows from continuity equation and Fick’s first law
- Can be derived from the one-dimensional random walk
- Predicts how diffusion causes the concentration to change with time
(dC/dx)= D(d^2 C/ dx^2) Fick’s second law
12
Q
Liquid diffusion coefficient
A
- Stokes showed that for a spherical particle, the drag force is related to size and solvent viscosity
- Liquid diffusion coefficients from the Stokes-Einstein equation: D = (kb*T)/f = kbT/(6π µr)
13
Q
Permeability vs. Diffusion
A
- permeability(filtration) = The rate of flow of a liquid or gas through a porous material
- Diffusion = The passive movement of molecules or particles along a concentration gradient
- Permeability depends on:
- diffusion coefficient (D)- P increases when D increases
- Membrane thickness (∆x) - P decreases when ∆x increases
- Partition coefficient (K) - P increases when K increases
- P = (KD/∆x)
14
Q
diffusion across the lipid bilayer
A
- Any molecules will eventually diffuse across a protein-free lipid bilayer down a concentration gradient
- The rate of diffusion depends on the size of the molecule and its hydrophobicity
- Small nonpolar molecules (O2, CO2) diffuse rapidly
- Small polar molecules (water, urea) diffuse slowly
- Lipid bilayer is highly impermeable to charged ions
- Membrane transport proteins are needed to allow essential molecules to pass through the lipid bilayer
- Ions, sugars, amino acids, nucleotides, cell metabolites
- Transporters: Bind a specific solute and undergo conformational changes to transfer the solute across the membrane
- Channels: Form aqueous pores that extend across the lipid bilayer, for example: aquaporins
- Much faster transport than transport via proteins
15
Q
Passive process: Diffusion
A
- Collisions cause molecules to move down or with their concentration gradient
- Difference I concentration between two areas
- Speed influenced by molecule size and temperature
- Nonpolar lipid-soluble substances diffuse directly phospholipid bilayer
- Certain lipophilic molecules are transported passively by: binding to protein carriers, Moving through water-filled channels
16
Q
Carrier-Mediated facilitated diffusion
A
- Transmembrane integral proteins are carriers
- Transport specific polar molecules (e.g., sugars and amino acids) too large for channels
- Binding of the substrate causes shape change in the carrier and then passage across the membrane
- Limited by the number of carriers present
- Carriers saturated when all engaged
17
Q
Channel-mediated facilitated diffusion
A
*Aqueous channels formed by transmembrane proteins
* Selectively transport ions or water
* Two types:
- Leakage channels: Always open
- Gated channels: Controlled by chemical or electrical
signals
18
Q
Passive Processes: Osmosis
A
- water concentration varies with the number of solute particles because solute particles displace water molecules
- Osmolarity: Measure of the total concentration of solute particles
- Water moves by osmosis until hydrostatic pressure and osmotic pressure equalize
- When solutions of different osmolarity are separated by a membrane permeable to all molecules, both solutes and water cross the membrane until equilibrium reached
- When solutions of different osmolarity are separated by a membrane impermeable to solute, osmosis occurs until equilibrium reached
- Osmosis causes cells to swell and shrink
- Change in cell volume disrupts cell function, especially in neurons
19
Q
Tonicity
A
- Tonicity: the ability of a solution to alter a cell’s water volume
- Isotonic: solution with the same non-penetrating solute concentration as cytosol
- Hypertonic: Solution with higher non-penetrating solute concentration than the cytosol
- Hypotonic: Solution with lower non-penetrating solute concentration than the cytosol
20
Q
Osmolarity
A
- Osmolarity: Measure of solute concentration
- Osmosis: Movement of water into or out of cells down a concentration gradient
- Sources of intracellular osmolarity:
- Macromolecules: Contribute very little to the osmolarity of the cell (few of them compared to small molecules)
- Charged, which attracts oppositely charged inorganic ions
- Counter ions make a major contribution to osmolarity
- Small organic molecules (sugars, amino acids, nucleotides):
- Both charged small molecules and their counterions contribute to osmolarity
- Osmolarity is mainly due to small organic ions
- Cell must control osmolarity or water will continuously move into the cell by osmosis
- Special case: Red blood cells
- No nucleus
- Plasma membrane with a high permeability to water
- High number of Na+ - K+ pumps for controlling cell volume
- If placed in a hypotonic solution (low solute, high water concentration):
- Water rushes into cell
- Cells burst
- If placed in a hypertonic solution (high solute, low water concentration)
- Water leaves cell
- Cells shrink
21
Q
Passive and active transport
A
- Passive transport (facilitated diffusion) allows solutes to pass the membrane inactively
- Uncharged molecule: Transport must be driven by concentration gradient
- Charged molecule: Transport drive by concentration gradient and electrical gradient
- Mostplasmamembraneshaveanelectricalpotential difference, inside is negative with respect to the outside
- Entryofpositivelychargedionsfavored
- Active transport: Transporter-mediated solute transport against an electrochemical gradient
- Requires energy input
22
Q
Membrane transport and channels
A
- Membrane channels allow passive transmembrane movement
- Membrane transporters can create large differences in intra- and extracellular concentrations
23
Q
transporter-mediated solute movement
A
- Uniporters: Mediate the movement of a single solute from one side of the membrane to the other at a rate determined by their Vmax and Km
- Coupled transporters: Transfer of one solute depends on the transport of a second
- Symporters (co-transporters): Simultaneously transport a second solute in the same direction
0 Antiporters (exchangers): Transfers a second solute in the opposite direction
24
Q
Membrane transport: active processes
A
- Two types of active processes: Active transport, Vesicular transport
- Both require ATP to move solutes across a living plasma membrane because
- Solute too large for channels
- Solute not lipid soluble
- Solute not able to move down a concentration gradient
25
Active membrane transport
* process by which a transporter transfers absolute across the lipid bilayer resembling an enzyme-substrate reaction
* each transporter has one or more binding sites for its solute
* cells link transporters to an energy source in three ways: coupled transport, ATP-driven pumps, Light-driven pumps
26
Active transport
* requires carrier proteins
- bind specifical;y and reversibly with substrate
* Moves solutes against a concentration gradient
- requires energy
* Two types:
- Primary active transport: NEED ATP HYDROLYSIS
- Secondary active transport: INDIRECTLY from ionic gradient created by primary active transport
27
Primary active transport
* energy from hydrolysis of ATP causes shape change in transport protein that "pumps" solutes(ions) across the membrane
* Sodium-potassium pump:
- carrier called Na, K ATPase
- located in the plasma membrane
- involved in primary and secondary active transport of nutrients and ions
28
Sodium-potassium pump
* Na and K channels allow slow leakage down a concentration gradient
* Na-K pump works as antiporter
29
Secondary active transport
* depends on ion gradient created by primary active transport
* energy stored in ionic gradients used indirectly to drive transport of other solues
* Cotransport- always transports more than one substance at a time
- symport system: substance transported in same direction
- Antiport system: substances transported in opposite direction
30
Ion gradient active transport
* the transfer of two solutes allows the coupled transporters to harvest energy stored in the electrochemical gradient
31
ABC Transport
* Cancer:
- multidrug resistance protein
- Able to pump hydrophobic drugs out of the cytosol
- Overexpressed in cancer cells
* Malaria:
- p.falciparum overexpress the ABC transporter that pumps out chloroquine
* Cystic fibrosis:
- Caused by a mutation in the gene encoding CTFR
- CFTR functions as a Cl- -channel in epithelial cells
- Irregular ion concentrations in the extracellular fluid
32
Vascular Transport
* Transport of large particles, macromolecules, and fluids across the membrane in membranous sacs called vesicles
* Requires cellular energy (e.g., ATP)
* Functions:
- Exocytosis—transport out of cell
- Endocytosis—transport into cell
* Phagocytosis, pinocytosis, receptor-mediated
endocytosis
- Transcytosis—transport into, across, and then out
of cell
- Vesicular trafficking—transport from one area or organelle in cell to another
33
Endocytosis and transcytosis
* Involve formation of protein-coated vesicles
* Often receptor-mediated, therefore very selective
* Some pathogens also hijack for transport into cell
* Once the vesicle is inside the cell it may
- Fuse with lysosome
- Undergo transcytosis
34
Endocytosis
* Receptor-mediated endocytosis
- allows specific endocytosis and transcytosis
- Clathrin-coated pits provide the main route for endocytosis and transcytosis
- different coat proteins:
- caveolae: captures specific molecules and use transcytosis
- Coatomer: Function in vascular trafficking
35
Exocytosis
* usaually actiavted by cell-surface signal or change in membrane voltage
* Substacne enclosed in Secetory vesicle
* v-SNAREs("v" = vesicle) on vesicle find
* t-SNAREs("t"= target) on membrane and bind
* function: hormone secretion, neurotransmitter release, mucus secretion, ejection of wastes
36
The Glyconcalux
* "sugar coating" at cell surface
* every cell type has a different pattern of sugars: which allows the immune system to recognize "self" and "non-self"
37
Cell junctions
* co
38
Tight junction
* Adjacent internal proteins fuse -> form impermeable junction encircling cell
* Where might this be useful? - endothelial cells, skin
39
Desomosomes
* "Rivets" or "spot-welds" that anchor cells together at plaques: linker proteins between cells connect plaques
* Where might these be useful? -tendons, ligaments
40
Gap junctions
* transmembrane proteins form pores that allow small molecules to pass from cell to cell
- for the spread of ions, simple sugars, and other small molecules between cardiac or smooth muscle cells
41
Cell environment interactions
* Cells interact directly or indirectly by responding to extracellular signals
* always involves glycocalyx
42
Roles of Cell Adhesion Molecules
* Thousands on approximately every cell in the body
* Anchor to extracellular matrix or each other
* Assist in the movement of cells past one another
* Attract WBCs to injured or infected areas
* Stimulate synthesis or degradation of adhesive membrane junctions
* Transmit intracellular signals to direct cell migration, proliferation, and specialization
43
Roles of Plasma Membrane Receptors
* Contacts Signaling: toughing and recognition of cells
* Chemical Signaling: interaction between receptors and ligands to alter the activity of cell proteins
44
Chemical signaling
* Ligand binding -> receptor structural change -> protein alteration
- Catalytic receptor proteins become activated enzymes
- Chemically gated channel-linked receptors open and close ion gates -> changes in excitability
- G protein-linked receptors activate G protein, affecting an ion channel or enzyme, or causing the release of internal second messenger, such as cyclic AMP
45
Membrane proteins
* integral proteins
- Firmly inserted into the membrane (most are
transmembrane)
- Have hydrophobic and hydrophilic regions
- Can interact with lipid tails and water
- Function as transport proteins (channels and carriers), enzymes, or receptors
46
Transport
* A protein that spans the membrane may provide a hydrophilic channel across the membrane that is selective for a particular solute
* Some transport proteins hydrolyze ATP as an energy source to actively pump substances across the membrane
47
Signal Transduction
* A membrane protein exposed to the outside of the cell may have a binding site that fits the shape of a specific chemical messenger, such as hormones
* When bound, the chemical messenger may cause a change in shape in the protein that initiates a chain of chemical reactions in the cell
48
Attachment
* elements of the cytoskeleton and the extracellular matrix may anchor to membrane proteins, which help maintain. cell shape and fix the location of certain membrane proteins
* Others play a role in cell movement or bind adjacent cells together
49
Enzyme activity
* a membrane protein may be an enzyme with its activation site exposed to substances in the adjacent solution
* a team of several enzymes in a membrane may catalyze sequential steps of a metabolic pathway as indicated
50
Cell-Cell junctions
* membrane proteins of adjacent cels may be hooked together in various kinds of intracellular junctions
* some membrane proteins of this group provide temporary binding sites that guide cell migration and other cell-to-cell interactions
51
Recognition
* some glycoproteins serve as identification tags that are specifically recognized by other cells
BME 533
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