Yogi Berra once noted that "You can observe a lot just by watching." A similar remark can be made about toys:
you can learn a lot of physics by playing with certain children's toys, and given that physics also applies to life,
you could hope that it would also be possible to learn about the physics of living cells by close observation of toys,
loosely defined. I'll start out with a couple of toys, rubber duckies and something called a soliton machine and
discuss insights (or failures) in how "energy" moves in biological molecules. I'll bring back the rubber duckies
and a toy suggested by one of the eccentrics known to roam the halls of academia to discuss how this lead to
studies how cells move and collective aspects of cell movement. Then I'll talk about mazes and how they lead to
experiments on evolution and cancer. Hopefully this broad range of toys will show how indeed "You can observe
a lot just by watching" about some of the fundamental physics of living cells.
We present, along with theoretical scaling arguments, measurements of the equilibrium and dynamic properties of λ and T2 phage DNA molecules confined in quartz nanochannels. Such measurements serve a two-fold purpose: (1) we hope to assist in the design of future nanofluidic devices by quantifying the behavior of semiflexible
polymers in confined environments and (2) we hope to test existing theories for confined semiflexible polymers.
We present an approach to fabricate an array of elastomer posts in order to dynamically measure the traction forces exerted by living cells on a surface with a micrometer lateral resolution. Arrays of closely spaced vertical microposts are made in silicone elastomer [poly(dimethylsiloxane) (PDMS)] by molding a Silicon substrate that has been machined by deep Si etching after standard photolithography. The surface of the micropillars was modified to allow cell culture. Deflections of the calibrated posts were dynamically followed by direct obervation with an optical microscope. By using this set-up, we could dynamically draw up a cartography of the local traction forces exerted by the cells.
A versatile free electron laser (FEL) user facility has recently come on line at the Thomas Jefferson National Accelerator Facility (Jefferson Lab) providing high average (kilowatt-level) power laser light in the infrared. A planned upgrade of the FEL in this facility will extend the wavelength range through the visible to the deep UV and provide the photobiology community with a unique light source for a variety of studies. Planned and potential applications of this FEL include: IR studies of energy flow in biomolecules, IR and visible imaging of biomedical systems, IR and visible studies of photodynamic effects and UV and near visible studies of DNA photodamage.
We show that myoglobin, which is almost entirely α helix in secondary structure, has an unusually long-lived 12 ps vibrational excited state lifetime generated by optically pumping at the blue side 5.85 microns of the amide I band, indicating the generation of a long-lived trapped soliton- antisoliton breather mode.
We will discuss two recent directions of our work: (1) The influence of submicron length scales on polymer dynamics, (2) Ultra-rapid mixing via sub-micron hydrodynamic focusing. (1) Polymer dynamics at sub-micron length scales. We have explored the changes in the dynamics of long polymers as the thickness of the quasi-2 dimensional space is varied from 0.09 microns to 10 microns. We will show how the thickness of this space, scaled with the persistence length of the polymer, changes the dynamics of the polymer. The consequences of this qualitative change in polymer dynamics is quite important, since it controls the elongation of the polymer at a given force field and hence the ability of he array to fractionate the polymer. (2) Mixing at the sub- micron length scale cannot be tubulent but only diffusive in nature. We will show how it is possible using hydrodynamics to produce liquid jets of width under 20 nanometers which can mix fluids in under 1 microsecond times.
We demonstrate a novel hydrodynamic shear activation of leucocyte adhesion, using physiological flow conditions and a microfabricated array of channels with length scales similar to those of human capillaries. Vital chromosome stains and cell specific fluorochrome labeled antibodies reveal that the eventual adhesion of the leukocytes to the silicon array displays a strong dependence on cell type and nuclear morphology, with granulocytes activating more rapidly with distance and penetrating a smaller distance than lymphocytes. Further, the granulocytes interact with the lymphocytes in a self-exclusionary manner under shearing flow with the eventual separation of the two cell types in the array. Such arrays of microfabricated obstacles thus have an interesting potential for sorting white blood cells by type from a 10 microliter drop of whole blood.
The Compact Infrared Free Electron Laser (CIRFEL) was built as part of a joint collaboration between Northrop Grumman and Princeton University to develop FEL's for use by researchers in the materials, medical and physical sciences. The CIRFEL was designed to laser in the Mid-IR and Far-IR regimes with picosecond pulses, megawatt level peak powers and an average power of a few watts. The CIRFEL utilizes an RF photocathode gun to produce high-brightness time synchronized electron bunches. The micropulse separation is 7 nsec which allows a number of relaxation phenomena to be observed. In addition, the photocathode illumination laser can be used in combination with the FEL IR light for pump- probe experiments. The CIRFEL is presently being commissioned and working towards lasing. The present status of the machine is presented.
There has been a significant financial effort poured into the technology of the Free Electron Laser (FEL) over the last 15 years or so. Much of that money was spent in the hopes that the FEL would be a key element in the Strategic Defense Initiative, but a small fraction of money was allocated for the Medical FEL program. The Medical FELs program was aimed at exploring how the unique capabilities of the FEL could be utilized in medical applications. Part of the Medical FEl effort has been in clinical applications, but some of the effort has also been put into exploring applications of the FEL for fundamental biological physics. It is the purpose of this brief text to outline some of the fundamental biophysics I have done, and some plans we have for the future. Since the FEL is (still) considered to be an avant garde device, the reader should not be surprised to find that much of the work proposed here is also rather radical and avant garde.
We provide a brief summary of current problems in DNA-protein interactions and argue that measurement of the elastic properties of DNA is critical to understanding these problems We discuss the ing1et depletion technique and various improvements we have been able to Achieve. Previous results using this technique are discussed, and we will present our plans for future experiments.