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.

‘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.

Silicon Brains, Photonics, etc.

The semester is officially over, which is exciting: I finally get to get back into the swing of research (with the occasional GRE study break, of course). As such, blogging will tend to be lighter; but before I lock myself in the lab, here are a few things that came to pass while I was busy finishing up the semester…

Building Brains in Silicon
Among other things, I wrote a paper for my computational neuroscience class on – you guessed it – some really cool work coming out of Kwabena Boahen’s group (formerly here at Penn, now at Stanford) on silicon-based artifical neural systems. This is sometimes classed as ‘neuromorphic engineering’, a term (coined by Carver Mead in the 1980’s) which has come to refer to a relatively recent interdisciplinary paradigm dealing with the development and study of artificial neural systems, drawing on principles from such fields as physics, biology, and computer/electrical engineering to design electronic-based analogues of biological systems. A number of people are using this to try to design new VLSI-based systems based on biological systems.

Some others are trying to reverse this scenario: while ‘real’ neural systems are experimentally studied by neurobiologists while grossly simplified ones are modeled by computational neuroscientists, groups like Boahen’s are trying to bridge these modes of inquiry by exploiting similarities between electronic and neural circuits. Mahowald and Douglas wrote a seminal paper in 1991 describing the first ‘silicon neuron’, and a good deal of work has gone on since then. For example, a number of ‘thermodynamic’ models of ion channels have been developed, building on concepts like Hodgkin/Huxley-type models. Anyway, by exploiting the beautiful similarity between ion channels and metal-oxide-semiconductor (MOS) transistors as two-state systems (simplistically, ion channels are either open or closed, with the energy barrier – and hence the transition rate – between the two states being modulated via, for example, a voltage; on the other hand, a voltage applied across the source and the drain of a MOSFET causes charges to diffuse through the ‘conduction channel’, with the effective barrier to this diffusion being modulated by a gate voltage), Boahen and his graduate student Kai Hynna have recently taken an important step toward ‘building a brain in silicon’. Using an approach that combines the advantages of experiment and artificial modeling, they have developed a simple electronic circuit that replicates the nonlinear dynamics of the gating particles of voltage-dependent ion channels.

References:
- Hynna and Boahen’s recent paper: K. M. Hynna and K. Boahen, Neural Computation 19, 327 (2007).
- 1991 silicon neuron paper: M. Mahowald and R. Douglas, Nature 354, 515 (1991).
- Thermodynamic models of ion channels: A. Destexhe and J. R. Huguenard, J. Comput. Neurosci. 9, 259 (2000).

Update: I guess Tech Review thought this stuff is cool, too: the latest issue has an article on Boahen’s work. It takes a broader view of his work than I have above - I just focused on one particular aspect.

Quasicrystals and Complex Materials as 3D Photonic Structures
I wrote another paper for my modern optics class, based on this recent experimental paper by Man, Megens, Steinhardt and Chaikin on three-dimensional quasicrystals as complete photonic bandgap materials. Here’s the deal: since Schrödinger’s wave equation and the electromagnetic wave equation are formally similar (neglecting spin statistics), it isn’t all that surprising that a number of analogies exist between electronic waves and light. In particular, electromagnetic waves can propagate in structures of periodic dielectric constant, and interference due to multiple Bragg reflections from these interfaces leads to directional-dependent energy band gaps. A major goal is to try to develop artificial structures to act as complete, omnidirectional photonic bandgap (PBG) crystals with bandgaps in the visible regime (wavelength ~ 400-700nm), and a lot of effort has gone into this. Interestingly, recent innovations in materials science and the study of complex materials – such as quasicrystals (QC), liquid crystals (LCs), and colloidal self-assembly – have breathed new life into this quest.

References:
- Experimental confirmation of the almost-spherical effective Brillouin zone (and hence the potential of developing a 3D PBG structure) of a macroscopic 3D icosahedral photonic QC: W. Man, M. Megens, P. J. Steinhardt and P. M. Chaikin, Nature 436, 993 (2005).
- Experimental approach towards assembling 3D analogues of the QC structures studied by Man et al. on a smaller scale using holographic optical trapping: Y. Roichman and D. G. Grier, Opt. Exp. 13, 5434 (2005).
- Another experimental approach, using a novel 7-beam optical interference holography technique: W. Y. Tam, Appl. Phys. Lett. 89, 251111 (2006).
- Using nematic liquid crystals in ‘inverse opal’ structures as PBG materials (tuned by parameters such as an external electric field) – for example, since liquid crystals are birefringent, modulating their orientational order using a field can influence their optical properties (a principle on which liquid crystal displays are based): K. Busch and S. John, Phys. Rev. Lett. 83, 967 (1998).
- Recent computational work has indicated a feasible method of fabricating 3D visible PBG crystals with two different types of lattice structure using self-assembly of a mixture of colloidal spheres of two different sizes: A. P. Hynninen, J. H. Thijssen, E. C. Vermolen, M. Dijkstra, and A. van Blaaderen, Nature Mater. 6, 202 (2007).

Talks Part 3: Biomaterials

Another talk that was particularly interesting was Angela Belcher’s Grace Hopper lecture on “Genetic Control of the Synthesis and Assembly of Materials for Electronics and Energy”. I’m not going to post much on it save for a number of references, because I’ve been aware of a lot of her group’s work for a good deal of time now. In general, what they do is try to combine man-made fabrication tools and the specificity inherent in living systems (via millions of years of evolution) to figure out easy, controllable, environmentally-friendly ways to make new materials for a variety of purposes. I was particularly struck by her emphasis on the simplicity of everything they do - if it can’t be transferred to industry or undergrad labs within several years, they won’t do it, which is an interesting philosophy. Anyway, one of the particularly cool things Prof. Belcher’s group has come up with recently is the use of viruses to direct the formation of nanowires, and they’ve been working to use them to make things like self-assembling, cheap and efficient Li-ion batteries. This kind of work definitely appeals to the part of me that likes science because of all the neat things that it enables us to make. Anyway, here are some of her publications that I’ve found most useful:

- B. D. Reiss et al., “Biological Routes to Metal Alloy Ferromagnetic Nanostructures“, Nano Lett. 4 1127 (2004).
- S. Jaffar et al., “Layer-by-Layer Surface Modification and Patterned Electrostatic Deposition of Quantum Dots“, Nano Lett. 4 1421 (2004).
- P. J. Yoo et al., “Spontaneous assembly of viruses on multilayered polymer surfaces“, Nature Materials 5 234 (2006).
- K. T. Nam et al., “Virus-Enabled Synthesis and Assembly of Nanowires for Lithium Ion Battery Electrodes“, Science 312 885 (2006).
- Y. Huang et al., “Programmable Assembly of Nanoarchitectures Using Genetically Engineered Viruses“, Nano Lett. 5 1429 (2005).
- C. Mao et al., “Viral assembly of oriented quantum dot nanowires“, PNAS 100 6946 (2003).