Why I’ve Switched to Biophysics

Along with moving to a new institution for my Ph.D., I have decided to switch fields, moving from hard condensed matter/ nanoscience to soft condensed matter/biological physics. This decision was totally unplanned - even when applying to and visiting graduate schools, I thought I wanted to do some variant of what I did as an undergrad. The thing is, as I visited more and more schools and learned about different people’s work, I found that what really captured my interest and got me excited was the biological side of things. Things tend to be messier and less well understood, but this just means that there’s more to learn and quantify, and I think physicists are well-positioned to bring something new and useful to the table.

Two months later, I’m spending all my time either reading about, talking to people about, or working on biology/biophysics experiments. It’s a lot of fun. Research-wise, I’m currently interested in the mechanics of cells and aggregates of cells (like biofilms); broadly speaking, I want to learn more about how they interact with each other and with their environment.

While in one sense my interest in soft condensed matter and biological physics has been steadily increasing over the past few years due to some really great classes I took as an undergrad, there are three key experiments or ideas that I’ve come across in the past two or three months that solidified my falling in love with this field.

1. Tensegrity and the structure of biological systems
Tensegrity is a mechanical design principle pioneered by Kenneth Snelson and Buckminster Fuller in the 1960’s, in which structures are designed such that the competition between forces - tension versus compression - throughout has a self-stabilizing effect. (A well-known example of this is the geodesic dome.) Among others, Don Ingber has spent a lot of time exploring the application of this idea to the structure of cells. Basically, the idea is that the cytoskeleton of the cell is composed of a network of interconnected units - the microfilaments, microtubules, and intermediate filaments - under tension and compression; that is, it is structured according to the principle of tensegrity. Many groups have explored this idea since it was first proposed, and other theories exist for understanding cellular structure; indeed, many groups, including the one I’m in, currently spend a lot of time trying to better understand the structure and physical properties of cells. (You can read more about this here.) I just thought the idea was so darn cool when I first came across it in this very nice Scientific American article written over a decade ago (look at the cell on page 54!). What’s more, this idea could be used to understand the structure of other assemblies at the micro- or nano-scale, such as buckyballs or nanotubes (e.g. see the chapter by Yakobson on “Carbon Nanotubes: Supramolecular Machines” in the Dekker Encyclopedia of Nanoscience and Nanotechnology), actuated nanocolumns, and even…

2. Viruses from a materials perspective
Yep - reading about tensegrity led to me to Caspar and Klug’s classical work in the 1960’s, in which they attempted to understand the structure of ’spherical’ viral capsids within a tensegrity-inspired framework. Since then, a number of physicists and engineers have spent a good deal of time trying to understand the structure of viral capsids. One framework in particular, developed by David Nelson and co-workers, really appeals to me: I think it’s an elegant combination of ideas from crystallography and continuum mechanics (what they call “spherical crystallography”). Basically, the idea is that if you try to pack a number of particles - be they beads, or the protein subunits of a viral capsid - on the surface of a sphere, the resulting assembly necessarily possesses crystallographic defects resulting from geometrical frustration. I wrote a small review of viral structure and mechanics focused on this work for a nanomechanics class not too long ago, which you can read here, if you want to explore this further. And this is just the tip of the iceberg - people are doing all sorts of crazy things with viruses: playing tug of war with them, watching them spit out their DNA, poking on them, shocking them, and filling them with various cargoes, among other things. Pretty cool stuff.

3. Hitting worms with laser pulses
Again, this is a very broad field in which a lot of great work has been (and continues to be) done. I don’t know enough about it. What first got me excited about biological neural networks and c. elegans was learning about this experiment by Mehmet Fatih Yanik. Basically, Yanik et al. used femtosecond laser pulses to cut single axons in c. elegans worms, observed the resulting phenotypic effects, and watched them grow back within 24 hours. This is pretty neat - after all, being able to perturb these affords researchers quite a lot of control, and could be used to study nerve regeneration processes one axon at a time, among other things. c. elegans is quite the model system, and I’m sure there’s a lot of other cool work going on trying to understand various processes and mechanisms in these worms. For example, in addition to Yanik’s work, my very little reading of research in this field has exposed me to some very interesting papers from Richard Morimoto’s, Ikue Mori’s, Aravi Samuel’s and William Bialek/William Ryu’s groups, to name a few off the top of my head. I still need to learn more about this field, particularly of what the biologists are doing - but again, this femtosecond laser stuff really got my attention when I first came across it.

Cool Papers 1: General

I’ve come across a number of pretty cool papers in the past few months. Some of them deal with particular phenomena (stay tuned for possible upcoming posts on molecules at surfaces, biomimetics, phononics, crystallization, nanoparticles, wetting phenomena, computational physics, etc. etc. - at some point), and so are probably better off getting their own blog posts. Here are a few papers that didn’t fall into specific categories…

1. Frictional Anisotropy on a Quasicrystal Surface
Along with ~10 other things, a subject that I’ve recently become interested in is nanoscale mechanics, broadly defined. A key experimental tool in this field is the use of local probes to push or pull on things controllably. Miquel Salmeron’s STM group at Berkeley does work on this and related subjects, and I finally got around to reading this paper of theirs from a few years back.

The idea is conceptually very simple: while friction unsurprisingly depends on commensurability (that is, if two surfaces in contact are structurally ‘complementary’, they will ‘lock in’ to each other and hence have high friction between them - an idea that apparently dates back to da Vinci), trying to think about friction using just this notion is unrealistic. For starters, most contacting surfaces are probably incommensurate, and other factors - such as periodicity(?) - contribute, as well.

This paper nicely singles out the role of periodicity by looking at different directions along Al-Ni-Co quasicrystal surfaces using STM (to image the surface and hence distinguish the periodic and aperiodic directions of atom ordering) and AFM (to measure the probe tip-surface friction along these directions) in ultra-high vacuum. The AFM friction data can be modeled using a classical model relevant to the experimental situation (the Derjaguin-Muller-Toporov or DMT model, which I need to learn more about), enabling key parameters to be derived from the measurements.

In particular, the authors find a larger friction force (8x) along the periodic direction than along the aperiodic direction. Unsurprisingly, they ascribe this to differences in energy dissipation via electron or phonon excitation+propagation along the different directions, although it is unclear to what extent each kind of excitation plays a role. Perhaps similar local-probe measurements of a different kind (e.g. ones sensitive to electrical versus mechanical properties) might be useful… At the end of the day, I like this paper because it is an elegant example of using a unique microstructure, in which just one variable (here periodicity) changes in ways that are well understood, to study something interesting as a function of just that variable.

2. Liquid Crystals and the Origins of Life
Noel Clark gave a great talk about this work here at Penn not too long ago. I won’t write too much about this since Randy has a nice description of it over at the condmat journal club.

Here’s the executive summary: according to extensions of Onsager’s rigid-rod model for the formation of liquid crystal phases, individual molecules must be sufficiently anisotropic (i.e. the aspect ratio has to be above a certain minimum) to form a liquid crystal (LC). Surprisingly, the authors of this paper observed LC phases consisting of single-stranded (ss) DNA molecules too short to satisfy this criterion. Optical and x-ray measurements indicate that this results from end-to-end stacking of duplexes of complementary short ss-DNA molecules (known as ‘living polymerization’) into larger rods that satisfy the Onsager criterion, even at low temperatures (in concentrated phases of duplexes separated from the isotropic phase of unpaired ss-DNA molecules).

This autocatalytic behavior is like positive feedback, in a sense, and is why this work is so interesting from a biological point of view: it provides a mechanism by which the right molecules can be ’selected’ out from a ’soup’, and ‘evolve’ into larger ones as part of an RNA world. It’s an interesting idea - definitely one that’s gotten a lot of press, it seems - and while this work doesn’t provide much hard evidence for it, I’ll be interested to see what it stimulates.

3. Suprafroth!
This is a very interesting paper out recently on the arxiv, I think to be published in Nature Physics. While I don’t understand all the details, I like this particularly because it’s a nice combination of ideas from soft- and hard-condensed matter physics, like electronic liquid crystals.

The authors used magneto-optical imaging, which I need to learn more about, to image the flux pattern of superconducting lead (a type-I superconductor). Turns out that the magnetic field on the edge of a disc-shaped sample of lead is larger than the actual applied field, and for large enough magnetic field some flux can penetrate the sample. This leads to a phase intermediate between the normal and superconducting phases, possessing a froth-like magnetic structure - specifically, the froth cell boundaries are superconducting, while the interiors are normal metal. This shows up very clearly in the magneto-optical images (see figures in the paper).

The nice thing is that, unlike ‘conventional’ froths, mass-transport processes like drying or drainage are not present here (as the authors point out, “this superconducting froth involves only electrons”). This means that the froth structure can be tuned reversibly using the applied magnetic field or temperature, and the nice magneto-optical images allow for quantitative analysis of the froth structure as a function of just these parameters.

This is philosophically similar (loosely speaking) to paper #1 - the friction measurements of quasicrystals: again, it is a very nice example of using a unique microstructure (here, a froth structure that doesn’t suffer from irreversible processes, and can be controlled by magnetic field or temperature) to study something interesting (here, the structure and dynamics of froths) as a function of just the variables that you can control.

4. Universality in Conference Registration
This is a cute correspondence recently sent to Nature Physics describing an intriguing social application of statistical mechanics.

The authors used registration data from two physics conferences (# of registrants as a function of time to the deadline), saw that they matched up remarkably well (after rescaling), and came up with a simple model to capture the observed phenomenon in which the ‘pressure’ felt by potential attendees to register varies inversely with respect to the time to the deadline. Also, incorporating a Boltzmann-like factor (instead of uniform probability to register over the period of time) leads to a prediction that agrees well with # of payments as a function of time to the deadline data.

Of course, there are a number of assumptions and fitting parameters floating around here, and I’m not entirely sure this work will change the world of physics, but I always find things like this fun.

PC to Mac

Yup, I’ve caved. I’ve been a PC user all my life, but the one I’ve had for the past several years has been slowly and steadily grinding to a halt, while my digital work load has equally been consistently rising, so it was time for a change. While I get the impression that switching to Mac is the new ‘in’ thing these days - IP has noted that new converts often favor style over functionality (and Macs are pretty, without a doubt) - my main reason was much more simple: it’s true, Macs generally do tend to be more stable, secure, and easy to use, and now with Boot Camp, I’m running Windows as well. There’s nothing to lose and a whole lot to gain, and for people like me who treat life as one giant optimization problem, that’s a big deal. Indeed, making the transition, transferring data, getting comfortable with (mostly) everything, &c. took under a week. Here’s how I do my ‘basic’ tasks…

• Presentations/Word Processing: MS Powerpoint & MS Word 2004. while I’ve heard good things about iWork, I went with MS Office simply because, at the end of the day, most of the files I work with (e.g. in collaborations) are Office files, and I wanted to make sure that I was 100% compatible (even though from what I hear, there aren’t too many major compatibility issues). I’m slightly regretting this now on the Word front (Powerpoint I can live with) - it’s notoriously slow at times. I’m trying to wait it out until Office 2008 for Mac comes out, but I may end up shelling out some more and get Pages (or something free, like OpenOffice).

• E-mail/Calendar: Apple Mail/iCal. Like everything else that came along with this machine, these are wonderful. Plus I can sync the iCal to my iPod, which is great (although I really do hate all these ‘i-’ prefixes).

• RSS reader: Vienna. Open-source, freeware, sleek, built-in browser, and tons of functionality. Works great.

• Plotting data: OriginLab/Plot/Apple Grapher. I’ve always used OriginLab for data analysis, making figures, &c. so I decided to install it on my Windows partition (sadly, no Mac version). However, I recently discovered Plot (a freeware program) and the built-in Grapher app, both of which are wonderful for making high-quality figures, both 2d and 3d. They’re very bare bones, which is great for what I use them for (I fought with Origin for a half hour the other day trying to format a polar plot correctly, whereas Grapher took five minutes to do the same thing).

• General data analysis: OriginLab/Igor Pro. Our lab has a license for Origin, and it’s what I’ve always used, so I installed it - but I wanted something I could run on my Mac as well, without having to switch to the Windows partition. I’ve hear some good things about Igor, and their amazing student personal purchase deal made it economical enough to buy. Haven’t had much chance to play around with it, though.

• AFM/SPM image analysis: Gwyddion, sometimes Image SXM. I do a lot of AFM/SPM image processing and analysis, and have so far tended to use Veeco’s Nanoscope software (again, which isn’t supported on Mac). I’m happy about that though, because I don’t think I would’ve ever bothered to try out Gwyddion, which is a wonderful piece of software. It’s freeware, has just about every kind of functionality imaginable, and best of all: it tells you what it’s doing (with excellent supporting documentation). Installing it is somewhat involved, but not too difficult. (The only major point to note is that Gwyddion for Mac OS X needs X11, which comes on the Mac installer disk). Oh, and before I installed Gwyddion I played around with Image SXM a bit, too - pretty nice as well, but I’m far more impressed with Gwyddion.

• Graphics: GIMP (the GNU image manipulation program). I used to use Adobe Photoshop for all my graphics needs, but it’s ridiculously expensive. This program does, as far as I can tell, pretty much everything Photoshop does - for free. (Again, like Gwyddion, it uses X11, which is a tool OS X uses to run certain open source programs). The only issue is that it’s not that great with certain very simple tasks, like - of all things - drawing a circle.

• Lab Notebook: VoodooPad. Another great free program with a ton of functionality - basically like a personal wiki that I plan to use as a lab notebook, but I haven’t used it enough to pass judgement. Very easy to use, though.

• Organizing Papers: Zotero. I tried the much-raved about Papers for a bit, but soon quit, because they only supported PubMed (which only includes a fraction of the journals I read). Now that they include Web of Science I’d be more inclined to stick with them, but Zotero’s been serving me wonderfully. It’s a simple firefox plug-in that supports pretty much every publisher I’ve encountered. It downloads a paper’s metadata (author list, journal, abstract, etc.) with a click of a button, and lets you store the paper as an attachment, too. Only two issues are (i) integration with Word is poor, but I can easily export my Zotero citations as an endnote file and use endnote to put in citations, as I’ve done before; (ii) data is only stored on this computer, not on some central server somewhere (although they claim to be working on including this, which will be great).

• Windows-in-Mac: None at the moment. A number of programs exist that enable one to use the Windows partition while in conventional Mac mode. I tried CrossOver briefly, but it didn’t work all that great. I plan on giving Parallels Desktop a shot at some point, but frankly, I haven’t really needed Windows all that much. (Which is probably the take-home message from this experience…)

Of course, if anyone has suggestions for good software or simply personal favorites, I’d love to hear about them.

All in all, no complaints so far, except for one, which is a slightly big one that I’m not sure what I’ll do about: it turns out that my laptop doesn’t work with certain kinds of projectors, which sucks when I have to give a talk. Quick googling reveals that this is a problem with many MacBooks, and that not much has been done to acknowledge or fix the problem, which is ridiculous. Particularly since I have to give a talk at a conference in a week or so… I’ll probably have to pdf it and carry it on a USB drive just in case things don’t work out, which stinks (and is definitely not a long-term solution).

Keeping Track of Publications

This is frustrating. While I’m usually pretty good with keeping up with the latest publications and preprints (via journals’ rss feeds), I like to follow the work of particular groups as well. I do this by going to the group’s webpage (which never works - hardly anyone seems to keep an accurate publication list) or searching on ISI Web of Science (which is far too time-consuming). ISI appears to have an option where they email you updates to your latest saved search, but I can’t figure out how to make it do what I want.

Ideally, there would be an online service (which covered all physics, chemistry, materials science etc. journals) which would allow me to input an unlimited number of author names, and would email me (or provide an rss feed) with updates to their citation record as they occurred. For free. Maybe such a thing already exists, but I haven’t found it.

Update: Via an overly complicated combination of stringing together search terms and saving histories, I managed to figure out a solution on ISI (I think - I’ll have to wait until the first email alert to be certain). As psi*psi points out, Yahoo Pipes may be a viable option, but I haven’t had the time to play around with it to figure out what it can and can’t do.

‘Hard’ measurements, ’soft’ materials

So it’s been what, a little less than two months since I last posted? I tend to work on many projects at once - some are ones I’ve been plugging away at for a while, while others are “let’s see what happens” experiments that I work on when I get the time, motivated by some half-brained idea. In particular, I’ve made significant progress on a project of the latter category, and the month-and-a-half has been spent making samples, furiously taking and analyzing data, trying to figure out what it means/delving through the literature, &c. - and of course, effectively disrupting any prospects of sleep or studying for pesky standardized tests. And making headway on my other projects, too. The good news is that I, for one, find the data pretty exciting.

(Oh, and moving to my sweet new apartment, which apparently scores a very respectable 98/100 on the walkability scale. Not too bad, especially given the relatively low rent.)

Anyway, when I haven’t been concentrating on my research, I’ve been reading up on things like organic semiconductors and STM modification of molecules (I suppose what one could call ‘hard’ condensed matter measurements of ’soft’ materials, although admittedly some of my own research falls into this genre). I find people like Paul Chaikin, Heinrich Jaeger and George Gruner particularly fascinating since they seem to be actively doing this kind of research in addition to hard condensed matter physics of the more ‘traditional’ kind (superconductivity/correlated electron systems…). I wonder how many other PIs do this kind of thing?

And of course, two new additions to the reading list: “charge transfer on the nanoscale: current status“, and “electrostatic modification of novel materials” - both hefty reviews of topics relevant to this post.

Also: Heinzel’s book on mesoscopic physics is a new addition to my list of the greatest books of all time - in particular, its clarity is unmatched by many other books I’ve come across on the subject.