1. CHAPTER 7
MEMBRANE STUCTURE
AND FUNCTION

2. Learning Objectives
How the cell membrane is an effective border for the cell allowing for transport
What are the different modes of transport
What define the particulars of what is transported

3. Introduction Plasma membranes enclose all living cells
Boundary that separates the cell from the non-living surroundings
Selectively permeable-constant exchange between cell and environment
Internal membranes have same types of functions-regulate passage of material

4. Hydrophobic region of protein
Most current model of membrane structure
Fluid mosaic model
Proposed by Singer and G. Nicolson in 1972
Membranes composed primarily of two types of macromolecules: lipids and proteins
Most abundant lipids are phospholipids
Mosaic of proteins molecules suspended (or embedded) in a fluid bilayer of phospholipids
Animation:
Hydrophobic region
of protein
Phospholipid
bilayer
Hydrophobic region of protein
Figure 7.3

5. LIPIDS: form matrix of membrane
Three types of lipids in membranes
Phospholipids
Structure?
Amphipathic molecules
DEF: have both hydrophilic and hydrophobic regions
Not just phospholipids but other membrane lipids and proteins

6. Behavior of phospholipids in water
Bilayer is basic membrane structure
Two monolayers thick
Orient with heads out and tails in--forming hydrophobic center
WATER
Hydrophilic head
Hydrophobic center
monolayer
WATER
Hydrophilic head
Figure 7.2

7. (c) Cholesterol within the animal cell membrane
Orientation in membrane
Amphipathic molecule: rings are hydrophobic and -OH is hydrophilic
Figure 7.5
(c) Cholesterol within the animal cell membrane
Cholesterol

8. Glycolipids Sugar chain attached to two fatty acid tails
Orientation in bilayer
Always oriented to external environment
Figure 7.7
Glycoprotein
Carbohydrate
Microfilaments
of cytoskeleton
Cholesterol
Peripheral
protein
Integral
CYTOPLASMIC SIDE
OF MEMBRANE
EXTRACELLULAR
SIDE OF
MEMBRANE
Glycolipid

9. (a) Movement of phospholipids
MEMBRANES ARE FLUID
Fluidity
Phospholipids are held in place by many many weak hydrophobic interactions
Can move laterally in plane of membrane
Rarely flip-flop from one layer to other
Figure 7.5 A
Lateral movement
(~107 times per second)
Flip-flop
(~ once per month)
(a) Movement of phospholipids

10. Temperature and Membrane Fluidity
Membranes remain fluid as temperature decreases to a certain point
Then it solidifies
Temperature at which it solidifies depends upon lipid composition of membrane

11. Factors That Affect Membrane Fluidity
Fatty acid saturation
Type of hydrocarbon tail affects fluidity
Unsaturated fatty acids cause more fluidity because prevent tight packing of tails
Saturated fatty acids allow tails to pack tightly
Fluid
Viscous
Figure 7.5 B
Unsaturated hydrocarbon
tails with kinks
Saturated hydro-
Carbon tails
(b) Membrane fluidity

12. Membrane fluidity Cholesterol
Different effects at different temperatures
Warm temperatures, restrains movement of phospholipids - makes membranes less fluid
Cool temperatures, prevents tight packing & makes membranes more fluid
Fig. 7.5c
Cells can alter membrane lipids to compensate for changes in temp

13. Membrane Proteins
A membrane is a collage of different proteins embedded in the fluid matrix of the lipid bilayer
Fibers of
extracellular
matrix (ECM)
Glyco-
protein
Microfilaments
of cytoskeleton
Cholesterol
Peripheral
proteins
Integral
CYTOPLASMIC SIDE
OF MEMBRANE
Glycolipid
Carbohydrate
EXTRACELLULAR
SIDE OF
MEMBRANE

14. MEMBRANE PROTEINS
Membrane proteins also fluid--move more slowly but do drift in phospholipid sea
EXPERIMENT
Researchers labeled the plasma membrane proteins of a mouse
cell and a human cell with two different markers and fused the cells. Using a microscope,
they observed the markers on the hybrid cell.
RESULTS
Membrane proteins
Mouse cell
Mixed proteins after 1 hour
Human cell
Hybrid cell
CONCLUSION
The mixing of the mouse and human membrane proteins indicates that at least some membrane proteins move sideways within the plane of the plasma membrane.

15. Proteins in membranes
Proteins in lipid bilayer determine the specific functions of a membrane
Proteins in each membrane vary in structure and thus function
EX: plasma membrane and internal membranes of same cell have different compositions of proteins thus the membranes themselves have different functions
Membrane movie :

16. Two populations of membrane proteins
1. Integral proteins
Penetrate hydrophobic core of lipid bilayer, often completely spanning the membrane
Also called transmembrane proteins
Amphipathic:
Coiled into alpha helices
Hydrophobic regions of amino acids in contact with hydrophobic core of bilayer
Hydrophilic regions of amino acids toward center of helix which created a hydrophilic area across the membrane
EXTRACELLULAR
SIDE
N-terminus
C-terminus
CYTOPLASMIC
SIDE
a Helix
Figure 7.8

17. Which of the following best describes the structure of a biological membrane?
two layers of phospholipids with proteins embedded between the two layers
a mixture of covalently linked phospholipids and proteins that determines which solutes can cross the membrane and which cannot
two layers of phospholipids with proteins either crossing the layers or on the surface of the layers
a fluid structure in which phospholipids and proteins move freely between sides of the membrane
two layers of phospholipids (with opposite orientations of the phospholipids in each layer) with each layer covered on the outside with proteins
Answer: c

18. 2. Peripheral proteins Not embedded in lipid bilayer at all
Usually attached loosely to membrane surface through integral proteins
Cytoplasmic side: part of cytoskeleton
External side: part of ECM

19. MEMBRANE CARBOHYDRATES
Glycoproteins: proteins with sugars attached
usually branched oligosaccharides (fewer than 15 sugar monomers)
Found only on external side of plasma membrane or on cisternal side of endomembranes
Vary from species to species, individual to individual, and even from cell type to cell type within the same individual

20. Functions of membrane carbohydrates
Glycoprotein variation marks each cell type as distinct
EX: A, B, AB, and O blood groups
differ in external carbohydrates on red blood cells

21. Cell-cell recognition
Ability of a cell to distinguish one type of neighboring cell from another
Interact with surface molecules of other cells, facilitating cell-cell recognition
EX: cells recognize each other by keying in on surface molecules, which are usually carbohydrates attached to glycoproteins embedded in plasma membrane

22. Membrane Sidedness Membranes have distinct inside and outside faces
Two lipid monolayers may differ in lipid composition
Integral proteins oriented in a specific direction
Outer surface also has carbohydrates
Asymmetrical orientation begins during synthesis of new membrane--where?
endoplasmic reticulum
Fig. 7.10

24. Traffic Across Membranes

25. Basic functions of membranes
Physical boundaries
Interfaces
Selectively permeable
Optimum environment for chemical reactions
Six major functions of membrane proteins
Signaling molecule
Enzymes
Receptor
ATP
Signal transduction
(a) Transport
(b) Enzymatic activity
(c) Signal transduction

26. (d) Cell-cell recognition (e) Intercellular joining (f) Attachment to
Glyco-
protein
(d) Cell-cell recognition
(e) Intercellular joining
(f) Attachment to
the cytoskeleton
and extracellular
matrix (ECM)
Fig. 7-9df

27. Permeability of membranes
Membranes are selectively permeable
Permeability determined in two ways:
solubility characteristics of phospholipid bilayer
presence of specific transport proteins

28. Solubility characteristics of bilayer
Nonpolar (hydrophobic) molecules
Hydrophobic molecules are lipid soluble and easily cross membranes
EX: hydrocarbons and O2
[Overhead]

29. Polar (hydrophilic) molecules
Very small uncharged polar molecules
Can cross rapidly due to size (CO2)
Ions (small charged) and polar molecules pass with difficulty
EX: small molecules, like water, can usually cross but with difficulty
EX: larger critical molecules, like glucose and other sugars cannot cross by themselves
EX: Ions, whether atoms or molecules, and their surrounding shell of water cannot penetrate the hydrophobic core of most membranes
REM: lipid solubility only part of permeability of membranes

30. Transport Proteins
Proteins embedded in bilayer have key roles on regulating movement across membranes
Transmembrane proteins
Can act as hydrophilic channels that certain molecules or ions can use as a tunnel
Others bind to molecules and physically carry solutes across membrane
Each is specific as to what it will translocate
EX: glucose transport protein in the liver will carry glucose from blood to cytoplasm, but not fructose, its structural isomer

31. Now know that selectivity is determined by both lipid bilayer and transport proteins
Next need to understand what determines the direction of traffic across a membrane

32. Two Types of transport across membranes
Passive transport
Requires no energy
May require transport proteins but not always
Active transport
Requires both energy and transport proteins
Moves small molecules with transport proteins
Vesicle movement of substances into cell is also active transport

33. Passive transport is diffusion across a membrane
Diffusion = tendency of molecules of any substance to spread out in the available space
driven by kinetic energy (thermal motion or heat) of molecules
Molecules move randomly, however, movement of a population of molecules may be directional
Molecules of dye
Membrane (cross section)
Net diffusion
Net diffusion
Equilibrium
Figure 7.11 A

34. Diffusion
In absence of other forces, a substance will diffuse from area of greater concentration to area of lesser concentration, down gradient
Spontaneous process: free energy and entropy by creating a randomized mixture
Each substance diffuses down its own concentration gradient, independent of other substances
Figure 7.11 B
Net diffusion
Equilibrium

35. Cell membranes are selectively permeable
Diffusion across a biological membrane requires no energy from the cell
concentration gradient represents potential energy and drives diffusion
EX: O2 freely diffuses across membrane, since cell is always using O2, [O2] is always lower inside cell
So concentration gradient causes net movement of O2 into cell

36. Osmosis Which of the following statements about osmosis is correct?
If a cell is placed in an isotonic solution, more water will enter the cell than leaves the cell.
Osmotic movement of water into a cell would likely occur if the cell accumulates water from its environment.
The presence of aquaporins (proteins that form water channels in the membrane) should speed up the process of osmosis.
If a solution outside the cell is hypertonic compared to the cytoplasm, water will move into the cell by osmosis.
Osmosis is the diffusion of water from a region of lower water concentration to a region of higher water concentration.
Answer: c

37. OSMOSIS - PASSIVE TRANSPORT OF WATER
Water will diffuse across membranes in response to solute concentrations
Tonicity = measure of of [solute]
solutions with equal [solute] are isotonic
solution with lower concentration of solutes is hypotonic
solution with higher concentration of solutes is hypertonic
REM: these are comparative terms-always think of comparing solutions inside and outside of cell

38. When two solutions are isotonic
Direction of osmosis is determined by a difference in total solute concentration
kinds of solutes in the solutions do not matter
When two solutions are isotonic
water still diffuses but molecules move at equal rates from one solution to the other
with no net osmosis

40. Lower concentration of solute (sugar) Higher concentration of sugar
Fig. 7-12
Lower
concentration
of solute (sugar)
Higher concentration
of sugar
Same concentration
of sugar
10%
50%
H2O
Selectively
permeable
membrane
Figure 7.12 Osmosis
Osmosis

41. Effects of tonicity on cells
Figure 7.13
H2O
Lysed
Normal
Shriveled

42. Osmoregulation = water balance
For a cell living in an isotonic environment osmosis is not a problem
EX: marine invertebrates-live in salt water that is isotonic to them
Similarly, cells of most land animals are bathed in an extracellular fluid that is isotonic to cells
Organisms without rigid walls have osmotic problems in either a hypertonic or hypotonic environment and must have adaptations for osmoregulation to maintain their internal environment

43. EX: Paramecium, a protist, is hypertonic when compared to the pond water in which it lives
In spite of a cell membrane that is less permeable to water than other cells, water still continually enters Paramecium cell
To solve this problem, Paramecium have a specialized organelle, contractile vacuole, that functions as a bilge pump to force water out of the cell

44. PASSIVE TRANSPORT requires no energy two types of passive transport
Simple Diffusion
Hydrophobic (nonpolar) & small uncharged molecules move across membranes this way
Concentration gradient determines direction of movement : molecules always move down gradient
Also some small molecules cross the membrane through channel proteins

45. Simple diffusion through channel proteins
Channel proteins allow for fast transport of those small molecules that have difficulty
EX: water channel proteins, aquaprorins, facilitate massive amounts of osmosis
Figure 7.15
EXTRACELLULAR
FLUID
Channel protein
Solute
CYTOPLASM

46. 2. Facilitated diffusion
Transport proteins help many polar molecules and ions that are normally impeded by lipid bilayer of membranes to passively diffuse across membrane
Facilitated diffusion = passive movement of molecules down its concentration gradient via a transport or carrier protein

47. Mechanism of facilitated diffusion: Ping-pong!
Carrier (transport) protein has two conformations:
binding of solute to sites exposed to outside cause 3D conformation change that exposes those sites to inside
some classes of amino acids, choline, and glucose translocated by facilitated diffusion
Figure 7.15
Carrier protein
Solute

48. ACTIVE TRANSPORT Movement of solutes against concentration gradient
Requires transport or carrier proteins that are specific for solute
sometimes several proteins work as a molecular machine to accomplish this transport
Requires energy
Usually called “pumps” because moving solutes “uphill”

49. ATP as energy source
ATP supplies energy for most active transport pumps
Often works by shifting a phosphate group from ATP (forming ADP) to transport protein = process called ???
Causes a conformational change in transport protein that translocates (moves) the solute across membrane

50. EX: Sodium-potassium pump
Actively maintains gradient of sodium (Na+) and potassium ions (K+) across the membrane
Normally, higher [K+] inside cell and higher [Na+] outside cell
Na+/ K+ pump uses energy of one ATP to pump three Na+ ions out and two K+ ions in
Against concentration gradient of both K+
Na+
Inside
Outside
Membrane
Inside
Outside
Membrane
3Na+
2K+

51. How Na+/K+ pump works-most current model
Na+ binding stimulates
phosphorylation by ATP. 2
Na+
Cytoplasmic Na+ binds
to sodium-potassium
pump. 1
K+ is released and Na+
sites are receptive again;
the cycle repeats.
Phosphorylation causes the protein to change its conformation, expelling Na+ to the outside. 3
Extracellular K+ binds to the
protein, triggering release of the
Phosphate group.
Loss of the phosphate
restores the protein’s
original conformation. 5
CYTOPLASM
[Na+] low
[K+] high P
ATP
ADP K+
[Na+] high
[K+] low 6 4 4

52. Some pumps generate voltage across membranes
Voltage = electrical potential energy generated by a separation of opposite charges
Each cell has different concentrations of positively and negatively charged ions and other molecules on either side of plasma membrane
EX: More negative charges in cytoplasm compared to extracellular fluid
All cells maintain a voltage across their plasma membranes
called Membrane potential
ranges from -50 to -200 millivolts

53. Electrochemical Gradient
Since membranes have different charges inside and outside, there is not only a concentration gradient but there is also an electrical gradient = electrochemical gradient
a chemical force based in an ion’s concentration gradient
an electrical force based on effect of membrane potential on ion’s movement
So ions do not simple diffuse down their concentration gradient, but diffuse down their electrochemical gradient

54. Review passive transport active transport movie Other good animations:

55. Electrogenic Pumps
DEF: Special transport proteins that generate voltage gradients across a membrane
Store energy which can be used for work
Sodium-potassium (Na+/K+) pump in animals

56. Proton (H+) pumps Found in plants, bacteria and fungi
Intermembrane space
Thylakoid space
Found in plants, bacteria and fungi
In plasma membrane, actively transport H+ out of cell
In mitochondria cristae and thylaloids of chloroplasts, concentrate H+ behind membranes

57. Cotransport
Process where an ATP-powered pump that transports one solute can indirectly drive active transport of several other solutes using a different transport protein
solute that was actively transported will passively diffuse back through a different transport protein
its movement is coupled with active transport of another substance against its concentration gradient

58. Cotransport of sucrose driven by H+ gradient
Fig. 7-19
Cotransport of sucrose driven by H+ gradient – + – + H+
ATP H+ H+ H+
Proton pump + –
Diffusion
of H+ H+ – H+ + H+
Sucrose-H+
cotransporter
Figure 7.19 Cotransport: active transport driven by a concentration gradient H+ – +
Sucrose – +
Sucrose

59. LARGE MOLECULES AND VESICULAR TRANSPORT
Large molecules and particles cross the membrane via vesicles
Vesicles are formed:
As two lipid bilayers rearrange themselves and phospholipids fuse so that the two membranes become continuous
Or a localized region of membrane can sort of sink in to form a pocket that deepens and pinches off into the cytoplasm --and thus forms a vesicle

60. Types of vesicular transport
DEF: Exocytosis = Process of exporting material from cell by vesicles
Transport vesicle buds from Golgi apparatus and moved by cytoskeleton to plasma membrane
When the vesicle and plasma membranes membranes come in contact, the bilayers of each fuse and that releases the contents of the vesicle to the outside of cell

61. DEF: Endocytosis = Process of cell engulfing materials into cell by forming new vesicles from plasma membrane
A small area of plasma membrane sinks inward to form a pocket
As pocket deepens into plasma membrane deepens, it pinches in, forming a vesicle containing material that had been outside cell
Endocytosis is a reversal of exocytosis
Three types of endocytosis

62. 1. Phagocytosis
“cellular eating”; cell engulfs a particle by extending membrane (pseudopodia) around it and packaging it in a food vacuole
contents are digested when vacuole fuses with what organelle??

63. 2. Pinocytosis
“cellular drinking”, a cell creates a vesicle around a droplet of extracellular fluidnon-specific process
Fig. 8.19b

64. Receptor-mediated endocytosis
Very specific
Triggered when extracellular substances called ligands bind to special receptors in the membrane, usually transmembrane proteins
Membrane folds into cell and forms coated pit that ultimately pinches in to form a coated vesicle

65. Review of passive and active transport
Passive transport. Substances diffuse spontaneously
down their concentration gradients, crossing a
membrane with no expenditure of energy by the cell.
The rate of diffusion can be greatly increased by transport
proteins in the membrane.
Active transport. Some transport proteins act as pumps, moving substances across a membrane against their concentration gradients. Energy for this work is usually supplied by ATP.
Diffusion. Hydrophobic
molecules and (at a slow
rate) very small uncharged
polar molecules can diffuse through the lipid bilayer.
Facilitated diffusion. Many hydrophilic substances diffuse through membranes with the assistance of transport proteins,
either channel or carrier proteins.
ATP
Is receptor-mediated endocytosis passive or active transport?
Bioflix movie as review