Tag Archives: Trigger warning

Faulkner

Nothing exciting enough scientifically to post about this week, so enjoy this. “We have enough neurologists in the Air Force, please resign your commission as you will be assigned to the Army.” This was followed in May 1968 by an Army preference for assignment form so out of date, that if I extended my two year tour to four I could take my family with me to Vietnam. This at a time when we had 500,000 troops over there.

What to do? What I did was residency by day, and Scotch and Faulkner by night, while looking at my widow to be and two orphans to be.

If the world has you down, and if you think your life is hard, it’s time to read about Yoknapatawpha county, and life when it was really hard. It’s practically biblical. I’d start with “The Hamlet”, and continue through the trilogy. Well over half of Faulkner’s work takes place here, so the rest will make sense.

I don’t read novels anymore having seen far more of life as a doc than some pup half my age. Faulkner is different. It has the ring of truth.

He had eyes the color of stagnant water, and other such delights await you.

Trigger warning — the N word appears prominently. Even so after reading him, you’ll never be upset by microaggressions again.

Here’s how Faulkner introduces the place.

“The people .. came from the northeast, through the Tennessee mountains by stages marked by the bearing and raising of a generation of children. They came from the Atlantic seaboard and before that from England and the Scottish and Welsh Marches … They brought no slaves and no Phyfe and Chippendale highboys; indeed, what they did bring most of them could (and did) carry in their hands. They took up land and built one- and two-room cabins and never painted them, and married on another and produced children and added other rooms one by one to the original cabins and did not paint them either, but that was all. Their descendants still planted cotton in the bottom land and corn along the edge of the hills and in the secret coves in the hills made whiskey of the corn and sold what they did not drink. Federal officers went into the country and vanished. … County officers did not bother them at all save in the heel of election years. They supported their own churches and schools, they married committed infrequent adulteries and more frequent homicides among themselves and were their own courts, judges and executioners. They were Protestants and Democrats and prolific; there was not one Negro landowner in the entire section. Strange Negroes would absolutely refuse to pass through it after dark.”

Exactly the way I felt that September driving through Meridian Mississippi with Pennsylvania plates on my car on my way into the Air Force and I’m not Black.

https://en.wikipedia.org/wiki/Mississippi_civil_rights_workers%27_murders

How one membrane protein senses mechanical stress

Chemists (particularly organic chemists) think they’re pretty smart. So see if you can figure out how a membrane embedded ion channel opens due to mechanical stress. The answer is to be found in last week’s Nature (vol. 516 pp. 126 – 130 4 Dec ’14).

As you probably know, membrane embedded proteins get stuck there because they contain multiple alpha helices with mostly hydrophobic amino acids allowing them to snuggle up to the hydrocarbon tails of the lipids making up the lipid bilayer of the biological membrane.

The channel in question is called TRAAK, known to open in response to membrane tension. It conducts potassium ions. The voltage sensitive potassium channels have 24 transmembrane alpha helices, 6 in each of the tetramer proteins comprising it. TRAAK has only 8. As is typical of all ion channels, the helices act like staves on a barrel, shifting slightly to open the pore.

In this case, with little membrane tension, the helices separate slightly permitting a a 10 carbon tail ( CH3 – [ CH2 – CH2 – CH2 ]3 – ) to enter the barrel occluding the pore. Tension on the membrane tends decrease the packing of hydrocarbon tails of the membrane, pulling the plug out of the pore. Neat !! ! ! This is a completely different mechanism than the voltage sensing helix in the 24 transmembrane voltage sensitive potassium channels, and one that no one has predicted despite all their intelligence.

Trigger warning. This paper is by MacKinnon who won the Nobel for his work on potassium channels. He used antibodies to stabilize ion channels so they could be studied by crystallography. Take them out of the membrane and they denature. Why the warning? In his Nobel work he postulated an alpha helical hairpin paddle extending outward from the channel core into the membrane’s lipid interior. It was both hydrophobic and charged, and could move in response to transmembrane voltage changes.

This received vigorous criticism from others, who felt it was an artifact produced by the use of the antibody to stabilize the protein for crystallography.

Why the warning? Because MacKinnnon also used an antibody to stabilize TRAAK.

The whole idea of membrane tension brings up the question of just how strong van der Waals forces really are. Biochemists and molecular biologists tend to think of hydrophobic forces as primarily entropic, pushing hydrophobic parts of a protein together so water would have to exquisitely structure itself to solvate them (e.g. lowering the entropy greatly). Here however, the ‘pull’ if you wish, is due to the mutual attraction of the hydrophobic lipid side chains to each other, which I would imagine is pretty week.

I’m sure that these forces have been measured, and years ago I enjoyed reading about Langmuir’s work putting what was basically soap on a substrate, and forming a two dimensional gas which actually followed something resembling P * Area = n * R * T. So the van der Waals forces have been measured, I just don’t know what they are. Does anyone out there?

Nonetheless, some very slick (physical and organic) chemistry.