Why aren’t we all dead ?

Anslyn && Dougherty is even more fun than Clayden et. al.  It’s far more advanced, and I’m certainly glad I read Clayden first.  On p. 24 they talk about the polarizability of molecules, sonething distinct  from the dipole moment of the molecule.  Polarizability is the ability of the molecule’s electron distribution to distort in the presence of an electric field.  I was suprised to find that the usual suspects (e.g. water) aren’t that polarizable and that the champs are hydrocarbons.   They don’t say how polarizability is measured, but I’ll take them at face value.

We wouldn’t exist without the membranes enclosing our cells which are largely hydrocarbon.  Chemists know that fatty acids have one end (the carboxyl group) which dissolves in water while the rest is pure hydrocarbon.  The classic is stearic acid — 18 carbons in a straight chain with a carboxyl group at one end.  3 molecules of stearic acid are esterified to glycerol in beef tallow (forming a triglyceride).  The pioneers hydrolyzed it to make soap. Saturated fatty acids of 18 carbons or more are solid at body temperature (soap certainly is), but cellular membranes are fairly fluid, and proteins embedded in them move around pretty quickly.  Why?  Because most fatty acids found in biologic membranes over 16 carbons have double bonds in them.  Guess whether they are cis or trans.   Hint:  the isomer used packs less well into crystals — you’ve got it, all the double bonds found in oleic (18 carbons 1 double bond), arachidonic (20 carbons, 4 double bonds) are trans – this keeps membranes fluids as well.   No, they are cis — thanks to PostDoc for pointing this out.  The cis double bond essentially puts a 60 degree kink in the hydrocarbon chain, making it much more difficult to pack in a liquid crystal type structure with all the hydrocarbon chains stretched out.   Then there’s cholesterol which makes up 1/5 or so of membranes by weight — it also breaks up the tendency of fatty acid hydrocarbon chains to align with each other because it doesn’t pack with them very well.  So cholesterol is another fluidizer  of membranes.

How thick is the cellular membrane?  If you figure the hydrocarbon chains of a saturated fatty acid stretched out as far as they can go, you get 1.54 Angstroms * cosine (30 degrees)  = 1.33 Angstroms/carbon — times 16 = 21 Angstroms.  Now double that because cellular membranes are lipid bilayers meaning that they are made of two layers of hydrocarbons facing each other, with the hydrophilic ends (carboxyls, phosphate groups) pointing outward.  So we’re up to 42 Angstroms of thickness for the hydrocarbon part of the membrane.  Add another 10 Angstroms or so for the hydrophilic ends (which include things like serine, choline etc. etc.) and you’re up to about 60 Angstroms thickness for the membrane (which is usually cited as 70 Angstroms — I don’t know why).

Neurologists and neurophysiologists spent a lot of time thinking about membranes, particularly those of neurons.  In all these years, I’ve never hear anyone talk about hydrocarbon polarizability.  It ought to be a huge factor in membrane function.  Why?  Because of the enormous electric field across the membranes enclosing all our cells (not just our neurons).  The potential across the membranes is usually given as 70 milliVolts (inside negatively charged, outside positively charged).  Why is this a big deal?

Because the electric field across our membranes is huge.  70 x 10^-3 volts is 70 milliVolts.  70 Angstroms is 7 nanoMeters (7 x 10^-9) meters.  Divide 7 x 10^-3 volts by 7 x 10^-9 and you get a field of 10,000,000 Volts/meter.   If hydrocarbons are ever going to polarize they should in this environment.  The college physics book I bought for the Quantum Mechanics course a while ago — “Physics for Scientists and Engineers” 4th edition p. 662 talks about lightning.  The potential difference leading to the discharge is the same; 10,000,000 Volts.  This results in a much smaller electric field (probably by a factor of 1,000) because clouds aren’t 1 meter off the ground.

So why don’t our cells collapse and we die?  I don’t know.

Here are a few Physics 102 questions for the cognoscenti out there.

l. Potential difference is due to charge separation.  Assume a flat membrane 1 micron square and 70 Angstroms thick.  How much charge must be separated to account for a potential of 70 milliVolts.  Answer in number of charges rather than Coulombs.

2. Now let’s get real.  We’re talking about neuronal processes here.  So lets talk about a cylindrical membrane 1 micron long (remember that some neuronal processes — such as those going from your spinal cord to your big toe are a million times longer than this).  Diameters of our nerve fiber range from 1 micron to 25 microns.  Ignoring the complication of the myelin sheath, how much charge must be separated to produce a potential across the membrane of the neuronal process of 70 milliVolts.

The more you think about life, the more remarkable it becomes.

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Comments

  • Adolfo  On March 7, 2011 at 2:45 pm

    Interesting question. Perhaps it has some influence on cell death, have you checked this paper?

    http://www.springerlink.com/content/g030573221011gn5/

    But I think it is unfair to compare it with lightnings that way. The scale is completely different. One of the major problems moving chemical processes from the lab to the industry is the scale up. In order to compare processes in different scales we use adimensional numbers. Although I dont know which number could be used in this case, if there is actually one that exists.

  • Postdoc  On March 10, 2011 at 11:33 am

    Point of note: I believe the double bonds in the fatty acids you listed are cis, not trans.

  • luysii  On March 10, 2011 at 11:47 am

    You are quite right. How embarrassing. The cis double bond puts what is basically a 60 degree kink in the hydrocarbon chain, making it more difficult to pack into a liquid crystal type structure. I’ll change this.

    Thanks

  • Curious Wavefunction  On March 13, 2011 at 11:15 pm

    How much is the energy in a 10^6 field. Is it more than 100 kcal/mol?

  • Curious Wavefunction  On April 5, 2011 at 11:30 am

    Retread, recently I had a discussion with a physics professor of mine who has studied the breakage of covalent bonds in electric fields. I told him about your question and he said that based on their observations, it would take a field at least a thousand time stronger than the one you indicated to break the bonds in the membrane hydrocarbons.

  • luysii  On April 6, 2011 at 5:59 pm

    Interesting ! Hopefully you’ll be able to ask your old physics prof about the effects of this intense electric field on the molecules which actually comprise the plasma membrane. Forget the fact that 20 – 50% of the mass of the membrane is taken up by proteins and just concentrate on the lipids. Phospholipids account for at least half the plasma membrane lipids. All of them have a negative charge on their phosphate moiety. That’s it for phosphatidyl ethanolamine and phosphatidyl serine, but phosphatidyl choline is a zwitterion, with the negative charge on the phosphate and the positive charge on the NM3 group.

    Things become even more complicated when you realize that biologic membranes are bilayers, so any orientation of molecule A in the outer leaf due to the electric field should be exactly the reverse of molecule A in the inner leaf. This why there is good evidence that the lipids in the inner leaflet aren’t the same as those in the outer leaflet.

    Do the counterions associated with the phosphate screen the large electric field ?

    See if you can ask him about this.

    Here’s just a hint of the complexity involved

    [ Proc. Natl. Acad. Sci. vol. 99 pp. 1943 – 1948 ’02 ] Lipid asymmetry between the leaflets of the plasma membranes is found in ‘many’ eukaryotic cells. The amino phospholipids (phosphatidylserine, phosphatidylethanolamine) are found in the inner leaflet, while the choline phospholipids (phosphatidylcholine and sphingomyelin) are found mostly in the outer leaflet. This is true for the red blood cell. The only charged lipid in this group is phosphatidyl serine (which is negative). This makes the inner leaflet negatively charged.

    MBOTC4 p. 590 — Phosphatidylinositol is concentrated in the cytosolic monolayer. A variety of enzymes add phosphate (notably phosphatidylinositol 3 kinase ).

    3 distinct activities are involved in the regulation of membrane lipid asymmetry.

    (1) flippase — a MgATPdependent aminophospholipid translocase. It localizes phosphatidylserine and phosphatidylethanolamine to the inner membrane leaflet by rapidly translocating them from the outer to the inner leaflet against an electrochemical gradient. The stoichiometry between amino phospholipid translocation and ATP hydrolysis is close to one (how will the cell have enough ATP to do anything else? The flippase is inhibited by high calcium, and by pseudosubstrates such as vanadate, acetylphosphate and para-nitrophenyl phosphate, and by SH reactive reagents such as N-ethylmaleimide and pyridyldithioethylamine (PDA) a specific inhibitor of phospholipid translocation

    (2) floppase — moves phospholipids from inner to outer leaflet. It is less specific and much slower than flippase

    (3) scramblase — ATP independent. This enzyme facilitates bidirectional translayer movement of all phospholipids, resulting in a collapse of asymmetry. High calcium activates scramblase, and also inhibits flippase.

    What is the use of this membrane asymmetry — lack of it might be a symbol that a cell is in trouble and should be destroyed. Given the ATP requirements of flippase, maintaining the asymmetry takes a lot of metabolic energy. Appearance of phosphatidylserine on the outer surface of the plasma membrane serves as a trigger for macrophage recognition of apoptotic cells.

    Another possibility is that several regulatory and structural proteins including protein kinase C, annexin and membrane skeletal proteins (spectrin) are localized to the cytoplasmic face of the membrane through their interaction with phosphatidylserine.

    Disruption of lipid asymmetry leading to phosphatidylserine on the outer surface of the plasma membrane, creates a procoagulant surface on platelets.

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