Biocurious

/ a biophysics blog

Cell Biophysics in Current Biology

Posted 27 September 2009 by Andre under

The current issue of Current Biology has a special section on Cell Form and Physics that starts with a nice editorial by Florian Maderspacher. I wrote a review with my PhD advisor, Dennis Discher, for the issue that you can find here (or here [pdf] if that doesn’t work). Best of all, the articles seem to be freely available, at least for now.

The main point of our review is that for all the work identifying molecules that are associated with stiffness and force sensing, there has been relatively little progress towards understanding the actual force sensitive steps. That is, although it’s known that many proteins are recruited to focal adhesions when cells are stretched, and that others are phosphorylated and play a role in various signaling cascades, these processes themselves are not directly regulated by force—they are secondary players in mechanotransduction.

Recently there have been some interesting results showing that forced protein unfolding in several different contexts could be critical. We review some of this work and related work that points towards unfolding even in cases where it hasn’t been definitively demonstrated. Ultimately, it looks like there will not be a single cellular “mechanosensor” but instead a whole host of different mechanosensitive processes that contribute in different ways. There’s lots of room here for more work by physicists and I hope people continue to get interested.

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Across the Sea in England

Posted 26 September 2009 by Andre under

Having defended my thesis, I set off to England about a month ago to start a postdoc at the Medical Research Council Laboratory of Molecular Biology in Cambridge. I’m going to be working in Bill Schafer’s lab studying neuroscience using C. elegans as a model system. This is a pretty big switch for me, but it’s exciting to try to orient myself in a new field and identify some interesting and tractable problems. It can also be frustrating when you can’t follow a lot of what people discuss in talks, but I’m trying to take advantage of my naivety to start something a bit original. It’s great to be a scientist.

Cambridge itself has been beautiful so far. It’s certainly colder than Philly, but it hasn’t rained much at all, despite everyone’s warnings. We’ve even tried some punting (that’s me trying to steer).

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David Griffiths Educates us on Physics Education

Posted 6 September 2009 by Andre under &

David Griffiths is best known as the author a fantastic series of textbooks. His book on electrodynamics is a classic in North American undergraduate education, although I’ve been disappointed to learn that it’s not as well known in Europe. Since I enjoyed reading his texts so much, it was nice to see that he has an article in the latest edition of Physics World and even nicer to read it. Now that he’s retired, I get the impression that he’s just calling it like he sees it and it makes for a good read.

My parents were professors (history and zoology), and they firmly believed that the purpose of education is to show students “how to think”. When I began teaching, I quickly discovered that many of my students could think much better – or at any rate much faster – than I could. What distinguished me from them was that I knew things that they did not, things they had been led to believe they ought to want to learn. I adopted a less-exalted goal: I think the purpose of education is to pass along to the next generation the accumulated knowledge and wisdom of humankind, and my role as a teacher is to make that process as efficient and palatable as possible.
I have known people who are in some sense too smart to be clear; they cannot remember what it was like not to understand something, because, I suppose, they never had this experience. They may be outstanding physicists, but they do not belong in the classroom. (There are exceptions: the most brilliant physicist I ever encountered, the late Sidney Coleman, was also – by far – the best and clearest teacher.)

Interestingly, another of Sidney Coleman’s graduate students, Phil Nelson, also has a knack for clear and engaging textbook writing and lecturing. Apparently something of Coleman rubbed off on them both.

Read the rest of Griffiths’ polemic for the full story. I can’t resist one more quotation:

I can explain the conservation of momentum in 15 minutes, but three hours in the lab would only convince an honest student that the law is false.

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How Blood Clots Stretch

Posted 5 September 2009 by Andre under

If you cut yourself, a blood clot can save your life: platelets aggregate and fibrin fibers form a mesh that catches red cells and prevents you from bleeding out. If you have heart problems, a clot can also take your life: heart attacks are often the result of clots in the coronary artery. Just such a clot is shown below. This is a colorized electron microscope image of a thrombus that was removed from a heart attack patient. You can see the mesh of straight fibrin fibers in brown, activated platelets in gray, red cells in red, and a leukocyte in green.

colorized electron microscope image of a thrombus or blood clot

To do their job effectively, blood clots must have an open structure so that enzymes can diffuse in to break the clot down when it is no longer needed. This can be achieved with a stiff scaffold with lots of spaces between the structural elements. A scaffold of stiff structural elements would normally be stiff itself and probably also quite brittle, but one of the first things you’ll notice if you take a blood clot in your fingers is that it’s squishy and stretchy, something like a water-logged rubber (or hydrogel). The thing is, rubber is made of highly flexible, thermally oscillating chains that provide extensibility but they have very small pores that wouldn’t allow enzymes to diffuse through effectively. So how does fibrin balance the large pore sizes with high extensibility?

We argue in our paper in Science that protein unfolding gives fibrin’s stiff fibers an intrinsic extensibility. In other words, it is the unravelling of compact protein structures, possibly fibrin’s coiled-coils, that allow blood clots to stretch so far. We hypothesized that this would be the case when we published our single molecule study of fibrinogen mechanics a couple of years ago, but to nail it down, we had to look at several structural levels from the macroscopic (centimeter level), through the microscopic network structure, to the nanometer molecular level.

It seems then that fibrin has evolved a molecular structure that enables it to play its amazing role. It self-assembles in clots into an open network that stops blood flow but can also be broken down and avoids being brittle by having structural elements that unfold under force. It’s an amazing material, and you make it and break it all the time.

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Thesis Defended

Posted 22 July 2009 by Andre under

Commemorative graphic courtesy Marcel Brown (my brother):
The Chronic album cover, slightly modified

See original here.

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Dead tree scrolls

Posted 1 July 2009 by PhilipJ under

I have long wondered who, exactly, still reads the dead tree copies of journals. I don’t know a soul who wanders over to a library to get the latest journal articles. The library is now where you go for only those journal articles that have (annoyingly) not yet found their way into a digital format that is Internet-accessible. I also don’t know many people who have subscriptions to dead tree copies of most journals. I’ll see the odd Science and Nature sitting around the coffee tables in various departments, but I don’t know many who prefer to read their favourite journals that way. Besides, Science and Nature are filled with enough news articles and op-eds that they really are science magazines with a more general appeal. Something like the Journal of the American Chemical Society? Definitely not.

Which is why I was quite happy to hear that the American Chemical Society is gradually moving to an entirely online distribution method. As per Nature News,

In 2010, ACS members will no longer be able to buy print subscriptions of journals, and the publications division will monitor print renewals from institutional subscribers. In general, Susan King [senior vice-president of the ACS’s journals publishing division] foresees a “move beyond print to an electronic-only scientific publishing environment”.

Not only is printing a dead tree version of a journal an incredible waste of money (which is obviously the real reason for the change by the ACS), it’s also an incredible waste of paper. Most journal articles are not interesting to most people. Online browsing of Tables of Contents and only printing out the articles you find interesting is a much better (from every perspective!) way of reading the scientific literature.

Of course, there will be a few dissenters. In this week’s Nature, Francois Diederich argues for the print editions of journals. As member of the German chemical society and a senior editor for Angewandte Chemie, he claims “there is a risk that the quality of these prestigious journals [Angewandte, JACS, etc] could gradually decline to the standard of many of today’s web-only journals.”

I’m having a lot of trouble coming up with a rational reason why this might be the case. How does the application of ink to paper by people and machines unrelated to the actual writing, editing, and production of the articles have anything to do with the quality of the science presented in a journal? In fact, abandoning the inconvenient medium of paper will allow for more informative Materials and Methods sections and (hopefully) a reduction in Supplemental Information. A return to well-described and documented methodology is one of the distinct advantages of moving to paperless scientific publishing.

I suspect the reason Diederich is so opposed to the idea is more his initial claim of convenience: “[printed journals] provide distinct advantages in letting me browse their content (during breakfast at home, for example) and readily take in information, without the lengthy opening of individual web pages, article by article.”

In an age of wireless Internet connections and mobile computing, this is not a compelling argument for the continual waste of both money and trees.

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