Supplemental Lecture (98/03/28 update) by Stephen T. Abedon (abedon.1@osu.edu)

  1. Chapter title: Membranes
    1. A list of vocabulary words is found toward the end of this document
    2. Unbroken sheets of membranes surround and, in fact, define the external boundaries of cells. They are also found within eucaryotic cells, surrounding a number of cell components termed "membrane-bound organelles." Membranes are so important to life that all of cellular metabolism may legitimately be divided into that which occurs within the boundaries of a membrane (i.e., inside of cells), that which occurs outside of cells (i.e., extracellulary), and that which occurs across membranes.
    3. In fact, intracellular conditions and extracellular conditions often do not resemble each other because of the controlled movement of materials from one side of a membrane to the other. "Understanding how these movements occur is essential to understanding how a cell functions." (p. 96, Black, 1996)
    4. At its simplest a cell membrane consists of just self-assembling sheets of amphipathic lipid molecules, arranged in parallel: lipid bilayers. In this lecture we will consider the structure of lipid bilayers. In a subsequent lecture we will consider mechanisms of transport across lipid bilayers.
  2. Lipid bilayer [unit membrane]
    1. The lipid bilayer is the basic structural component of cell membranes.
    2. Lipid bilayers consist of two layers of predominantly phospholipids or other amphipathic, organic compounds arranged in sheets.
    3. Lipid bilayers self form because the hydrophobic ends of their constituent molecules face inward, packed together away from water, while the hydrophilic ends face outward, toward the water solvent (see micelles).
    4. The van der Waals interactions between the hydrophobic ends further stabilize lipid bilayeras well as help define the temperature-dependent fluidity of lipid bilayer.
    5. See text figure 1050.1 and the illustration below.
  3. Illustration, lipid bilayer
  4. Semipermeability
    1. Lipid bilayers are referred to as semipermeable because, while some substances can readily pass from one side of a lipid bilayers to the other, others do so only with great difficulty, if at all.
    2. For example:
      1. Small and/or hydrophobic substances pass through lipid bilayers with ease.
      2. Large and/or hydrophilic substances show minimal potential for crossing lipid bilayers.
      3. Lipid bilayers tend to be impermeable to such things as proteins and amino acids, nucleic acids, and carbohydrates.
      4. Lipid bilayers are permeable to many lipids, lipid-like substances, and gasses such as molecular oxygen.
    3. Water is exception:
      1. An apparent exception to these rules is that lipid bilayers tend to be very permeable to water.
      2. Water's small size apparently makes up for it's polarity.
  5. Illustration, semipermeable membrane
  6. Plasma (cytoplasmic, cell) membrane
    1. A cell, plasma, or cytoplasmic membrane is the semipermeable unit membrane surrounding, and defining the physical limits of a cell.
    2. Both procaryotes and eucaryotes have plasma membranes.
  7. Extracellular
    1. Extracellular is everything in the universe not including the inside of the cell in question.
    2. Practically speaking, the extracellular environment is that immediately surrounding a cell.
  8. Intracellular
    1. Intracellular is the volume within a cell membrane.
  9. Semipermeable cell membrane
    1. Selective holes or gates:
      1. Many substances are able to pass through semipermeable cell membranes that are not able to pass through lipid bilayers.
      2. This is because semipermeable cell membranes tend to have either selective or non-selective protein holes in them (in gram-negative bacteria, for example, plasma membranes have selective holes while outer membranes tend to have non-selective holes).
    2. Substances the cell needs inside may be readily passed through the cell's membranes (often at the cost of energy--especially if the substance is being transported against a concentration gradient) and waste products may be passed out of the cell. (See illustration below.)
  10. Illustration, cell (biological) membrane
  11. Membrane proteins
    1. In addition to amphipathic lipid-based molecules (such as phospholipids), cell membranes have associated proteins.
    2. These proteins attach to membranes in a variety of ways, which basically fall into two general categories:
      1. integral membrane proteins
      2. peripheral membrane proteins
    3. Integral membrane proteins:
      1. Integral membrane proteins are those spanning the membrane in some manner, thus attached in the same manner as the amphipathic, lipid-based molecules within the membrane.
      2. Usually about 70 to 80% of membrane proteins are integral membrane proteins.
      3. These membrane proteins tend to be not easily extracted from membranes and also tend to be insoluble in aqueous solutions absent, for example, the presence of detergents.
      4. These are the proteins which are particularly involved in transport across membranes.
      5. (see simplistic illustration of a membrane spanning protein above).
    4. Peripheral membrane proteins:
      1. Peripheral membrane proteins are those that do not span the membrane but instead are bound either to amphipathic lipids-based molecules or proteins that span the membrane.
      2. Usually about 20 to 30% of membrane proteins are peripheral membrane proteins.
    5. Membrane proteins supply the means by which various substances, that would otherwise demonstrate minimal permeability, may cross lipid bilayers.
    6. Membrane proteins may also exert control over the direction of travel of these substances.
    7. This is done particularly by expending energy to force solutes to move against concentration gradients.
    8. Membrane proteins thus play important roles in the concentrating of solutes on one side of a membrane relative to the other.
    9. Note that concentrating solutes, with or without the use of membranes, is an energy requiring task.
    10. Cell membranes also serve as anchor points for a variety of proteins whose functions have little to do with the cross-membrane transport of substances.
  12. Membrane asymmetry
    1. Different composition inside and out:
      1. It is important when thinking about membranes to keep in mind that a typical cell membrane tends to have a different composition on one side (a.k.a., leaflet; say, the inside, or inner leaflet) than on the other (the outside, or outer leaflet).
      2. Differences tend to include different ratios or types of amphipathic lipid-based molecules found in each leaflet, different kinds of proteins facing in or facing out, or fixed orientations of proteins spanning the membrane.
    2. Automatically adjusts solute concentrations:
      1. This asymmetry allows the cell to automatically differ its intracellular environment from that existing extracellularly.
      2. As might therefore be expected, asymmetries tend to be rigidly maintained.
  13. Fluid mosaic model
    1. More liquid than solid:
      1. Our discussion of lipid bilayers so far has considered them only as flexible but otherwise unchanging sheets of molecules. In fact, like the water in which they are contained, and as alluded to in our discussion of oils, cell membranes are more a kin to liquids than to solids.
      2. "The emerging picture of the cell membrane is one of a highly organized and assymetric system, which also is flexible and dynamic." (p. 44, Prescott et al., 1996)
    2. Lateral movement:
      1. Phospholipids generally show a significant ability to move laterally within phospholipid sheets.
      2. Proteins, too, unless anchored in place, can move laterally in membranes (though with less speed owing to their larger size).
    3. Minimal flipping:
      1. Spontaneous flipping of phospholipids and membrane proteins from one leaflet of a membrane to the other tends to be a very unlikely occurrence.
      2. Cell membranes (lipid bilayers), thus rigidly maintain their approximately two-dimensional (plane-like) structure while allowing significant movement within layers.
  14. Links ---
    1. Membrane Biophysics
  15. Vocabulary
    1. Cell membrane
    2. cell (biological) membrane, illustration
    3. Cytoplasmic membrane
    4. Extracellular
    5. Fluid mozaic model
    6. Intracellular
    7. Lipid bilayer
    8. Lipid bilayer, illustration
    9. Membrane asymmetry
    10. Membrane proteins
    11. Plasma membrane
    12. Semipermeable membrane
    13. Semipermeable membrane, illustration
    14. Unit membrane
  16. Practice questions
    1. Which of the following are lipid bilayers permeable to? (circle correct answer) [PEEK]
      1. proteins
      2. molecular oxygen
      3. amino acids
      4. nucleic acids
      5. carbohydrates
      6. ions
      7. all of the above
      8. none of the above
    2. What aspect of water renders lipid bilayers permeable to it? [PEEK]
    3. An organic compound with which of the following properties would you expect to be able to cross a lipid bilayer? [PEEK]
      1. size of glucose, lipid soluble
      2. size of glucose, positive charge
      3. glucose
      4. size of glucose, fatty acid salt
      5. starch
      6. sodium ions
    4. Neatly draw a lipid bilayer (i.e., no proteins) making sure to convince me that you understand how the properties of phospholipids contribute to its structure. [PEEK]
    5. True or False, semipermeable lipid bilayers are permeable to water molecules as a consequence of the water molecule's hydrophilicity (circle correct answer). [PEEK]
    6. What aspect of cell membranes supplies the means by which "various substances may cross lipid bilayers that would otherwise demonstrate minimal permeability?" ([PEEK]
    7. What aspect of a semipermeable, membrane protein containing, lipid bilayers (such as that serving as a bacterial plasma membrane) assures that the environment on one side of this membrane differs from that on the other side? ([PEEK]
    8. Why is it so relevant to the biology of cells that membrane proteins display extremely minimal "flipping" from one orientation (e.g., inside to out orientation) to the other (e.g., outside to in). ([PEEK]
    9. In how many dimensions are lipid bilayers typically fluid? (circle best answer) [PEEK]
      1. 0
      2. 1
      3. 2
      4. 3
      5. 4
      6. more than 4
    10. Given a continuous bag (no leaks) whose walls consist of pure lipid bilayer (i.e., phospholipids are the only component). The bag was created in pure water (to which only phospholipid was added and recalling that phospholipids are capable of forming such bags spontaneously; furthermore, assume that all of the phospholipids became incorporated into lipid bilayers). Therefore the bag initially displayed an interior environment which was chemically identical to the exterior environment. Sugar (e.g., glucose) was subsequently added to the exterior environment (i.e., after rather than prior to or during bag formation). Describe the interior chemical environment (its volume, not its walls) of the "bag" following sugar addition. [PEEK]
    11. Describe the consistency (e.g., solid, liquid, gas) that you would expect a functional lipid bilayer to have, at the temperature at which the organism containing them evolved. [PEEK]
    12. Distinguish integral membrane protein from peripheral membrane protein, employing descriptive terms other than "integral" and "peripheral". [PEEK]
    13. Name or describe a role integral membrane proteins play in controlling the internal chemical environment of a cell (e.g., a mechanism which integral membrane proteins effect which is otherwise lacking in protein-less lipid bilayers)? [PEEK]
    14. Give examples of (i) two things (or types of things or properties of things) which can typically cross lipid bilayers, and (ii) another two things (or types of things or properties of things) which typically cannot. [PEEK]
    15. Bio 113-only:
      1. The multisubunit protein hemoglobin plays a significant role in body metabolism since it is the blood carrier of molecular oxygen. Carbon monoxide, a poisonous gas which consists simply of one carbon and one oxygen atom (CO), competitively inhibits hemoglobin's ability to carry oxygen. Once a significant fraction of hemoglobins have been bound by CO, death can ensue as a consequence of oxygen starvation. Given that hemoglobin is found primarily within red blood cells, give me a reason (which is independent of extracellular concentrations) why carbon monoxide may reach hemoglobin to interact with it at a rate which is lower than that accomplished by molecular oxygen (O2, i.e., OO).[PEEK]
  17. Practice question answers
    1. ii, molecular oxygen
    2. small size
    3. i, size of glucose, lipid soluble
    4. lipid bilayer with hydrophilic ends of phospholipids (circles) pointing out on both sides and hydrophobic tails (two) pointing in.
    5. False, it is their small size that makes the difference. Hydrophilic substances tend not to be able to cross lipid bilayers, though the small size of water molecules is able to make up for the definitively high hydrophilicity of water molecules.
    6. membrane proteins
    7. The existence of asymmetry within this membrane, i.e., proteins display a fixed polarity within the membrane, moving each kind of substance only unidirectionally, thus concentrating that substance on one side relative to the other.
    8. Membrane asymmetries (which are defined to a significant extent by fixed membrane protein orientations) coupled with appropriate energy expenditure automatically maintains the internal cell environment at different solute concentrations relative to those found in the extracellular environment.
    9. iii, 2. They are sheets, which, like the sheets that lie on your bed, means that they are essentially planes, which in turn are the two dimensional surfaces you studied in geometry. Another way of saying this is that movement is constrained to two directions, with infinite gradiations in between. Missing is the third dimension: Movement of membrane components out of the plane of the membrane. Hence, movement is constrained to two dimensions.
    10. pure water; if you want to get fancy you might also note that the "bag" displays a reduced volume as a consequence of the creation of a hyperosmotic environment upon sugar addition. The key point is that the sugar is not going to be able to cross the otherwise semipermeable lipid bilayer.
    11. It would be fluid (soft, liquid, etc.) to the touch, i.e., fluid mozaic model (hard, solid, etc. would not be appropriate answers).
    12. An integral membrane protein spans the membrane where a peripheral membrane simply adheres to the membrane's surface
    13. Integral membrane proteins control what crosses membranes; integral membrane proteins serve as channels and effectors of various kinds of across membrane transport (other than simple diffusion across lipid bilayers); some integral membrane proteins are also capable of effecting the concentration of substances on either side of the membrane
    14. (i) small or hydrophobic things generally can cross lipid bilayers (water, uncharged lipds) whereas (ii) large or hydrophilic things (especially charged things) typically cannot (sugars, amino acids, proteins, nucleic acids, etc.)
    15. CO is a more polar molecule than molecular oxygen and hence less able to dissolve in and therefore less able to pass through the red blood cell plasma membrane lipid bilayer.
  18. References
    1. Black, J.G. (1996). Microbiology. Principles and Applications. Third Edition. Prentice Hall. Upper Saddle River, New Jersey. pp. 82-84, 96-98.
    2. Mathews, C.K., van Holde, K.E. (1990). Biochemistry. The Benjamin/Cummings publishing co., inc. Redwood City, CA. pp. 298-332.
    3. Prescott, L.M., Harley, J.P., Klein, D.A. (1996). Microbiology. Third Edition. Wm. C. Brown Publishers, Dubuque, IA. pp. 43-44.
    4. Raven, P.H., Johnson, G.B. (1995). Biology (updated version). Third Edition. Wm. C. Brown publishers, Dubuque, Iowa. pp. 107-118.
    5. Tortora, G.J., Funke, B.R., Case, C.L. (1995). Microbiology. An Introduction. Fifth Edition. The Benjamin/Cummings Publishing, Co., Inc., Redwood City, CA, pp. 82-87.