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Computed and Measured Forces Among Membranes, Nanoparticles, and Macromolecules
- V. Adrian Parsegian, PhD, Head, Section on Molecular Biophysics
- Jason E. DeRouchey, PhD, Postdoctoral Fellow
- Rudolf Podgornik, PhD, Visiting Scientist
- Xiangyun Qiu, PhD, Postdoctoral Fellow
With a long-term goal to build a practical physics of biological material, we in the Section on Molecular Biophysics measure, characterize, and codify the interactions that govern the organization and self-assembly of various of biological molecules. Connected in part with the recent NIH-wide interest in nanotechnology, we are building on our experience with van der Waals fluctuation forces to formulate interactions involving carbon nanotubes not only in their assembly but also, and more important, as substrates for biopolymers such as DNA. Our undertaking is strengthened by its strong connection with physical theory. Through a series of measurements and analyses of the different kinds of interactions as revealed in vivo, in vitro, and in computation, we are working with DNA assemblies such as those seen in viral capsids and in vitro, polypeptides and polysaccharides in suspension, and lipid/water liquid-crystals. In these systems, we simultaneously observe the structure of packing as well as measure intermolecular interaction energies. We have also worked with experimentalists who are able to create repulsive as well as attractive charge fluctuation forces, with implications for nanotechnology.
van der Waals forces
Despite the fact that van der Waals forces are the dominant interaction that coheres membranes and proteins, the source of the powerful surface tension at membrane interfaces, as well as the attraction that creates membrane multilayers or allows membranes to adhere to artificial surfaces, they are only now being studied in a systematic collaboration between quantum physicists and biophysicists. This year, we used the quantum mechanical density functional theory (DFT) solved for several carbon nanotubes to compute the forces that cause them to cohere as well as serve as a substrate for many materials. It is remarkable that quantum chemistry combined with our expertise on macromolecular interactions is allowing us to see properties such as torque as well as force between carbon nanotubes.
The key has been to begin with the elements of physical theory that relate the polarizability of materials to the fluctuations of charges within them. From this, we were able to design experiments that show how macromolecular organization responds to deliberate changes in solution properties. Progress is thus through a tight coupling of modern quantum theory of structured materials with experiments and measurements that reveal electromagnetic properties.
To formulate and to compute van der Waals forces involving lipids, water, and ions, as well as synthetic structures such as carbon nanotubes, we teamed with groups that measure absorption spectra. The results showed how charge fluctuation forces conferred by ions in solution can modify forces between lipid membranes. We measured those forces as well as computed van der Waals charge fluctuation forces in those same systems.
We also progressed in extending the Lifshitz theory of van der Waals interactions to stratified media such as lipid multilamellar systems, permitting us to compute forces between bodies with extended interfaces. These can range from the practical—the composite media of electric insulators—to the biological—the action of extended polymer layers on biological membranes.
We have been able to measure repulsive van der Waals forces in systems in which the properties of the medium are intermediate between those of the interacting bodies. The resultant ability to create switchable systems has exciting implications for nanotechnology.
Molecular assembly in vitro and in viruses
Beginning with direct measurements of forces between large molecules, proceeding with observations of molecules under confinement, and building on the statistical physics of molecular organization under the action of organizing forces, we have developed new theories and new methods of macromolecular organization. Among these are the observations of DNA under the osmotic stress of large polymers or confined within the hard walls of a virus capsid.
Our most recent work has been to observe the ejection of DNA from capsids subjected to varying salt conditions. Expansive pressures can vary up to many tens of atmospheres, a pressure that is responsible for initial ejection of DNA. These forces can be varied by ionic conditions. An unrecognized feature of many viruses is that these conditions can penetrate the virus and, in fact, modify the expansive force within. At one extreme, DNA in simple salts will be under great pressure to expand and be ejected from the capsid; but, under other conditions—under which DNA-condensing ions can enter the capsid—DNA can be under no expansive pressure. We have begun to measure the motion of DNA within capsids subject to differing ionic conditions and to see how ejection might be controlled by ionic surroundings, with the goal of determining whether these manipulations ultimately affect viral infectivity.
To see the connections between DNA pressure and ejection, we have been growing viruses of various lengths to be placed within the same-size capsid. Using X-ray diffraction, we are able to follow the packing and the pressure of DNA within the capsid. We have also succeeded in following the condensation of triple-helical DNA, implicated in the behavior of telomeres. The response to various divalent ions in different tsDNA constructs revealed differences in packing and liquid crystalline tendencies.
Publications
- Rajter RF, French RH, Podgornik R, Ching WY, Parsegian VA. Spectral mixing formulations for van der Waals London interactions between multicomponent carbon nanotubes. J Appl Phys 2008 104:053513.
- Evilevitch A, Fang LT , Yoffe AM, Castelnovo M, Rau DC, Parsegian VA, Gelbart WM, Knobler CM. Effects of salt concentrations and bending energy on the extent of ejection of phage genomes. Biophys J 2008 94:1110-1120.
- Cohen JA, Podgornik R, Hansen PL, Parsegian VA. A phenomenological one-parameter equation of state for osmotic pressures of PEG and other neutral flexible polymers in good solvents. J Phys Chem B 2009 113:3709-14.
- Gurnev PA, Harries D, Parsegian VA, Bezrukov SM. The dynamic side of the Hofmeister effect: a single-molecule nanopore study of specific complex formation. Chemphyschem 2009 10:1445-9.
- Munday JN, Capasso F, Parsegian VA. Measured long-range repulsive Casimir-Lifshitz forces. Nature 2009 457:170-3.
Collaborators
- David Andelman, PhD, Tel Aviv University, Tel Aviv, Israel
- Sergey M. Bezrukov, PhD, Program in Physical Biology, NICHD, Bethesda, MD
- Federico Capasso, PhD, Harvard University, Cambridge, MA
- Wai-Yim Ching, PhD, University of Missouri, Kansas City, MO
- Joel Cohen, PhD, University of the Pacific, San Francisco, CA
- Roger French, PhD, University of Pennsylvania, Philadelphia, PA
- William Gelbart, PhD, University of California Los Angeles, Los Angeles, CA
- Philip A. Gurnev, PhD, Program in Physical Biology, NICHD, Bethesda, MD
- Per Lyngs Hansen, PhD, Syddnask Universitet, Odense, Denmark
- Charles Knobler, PhD, University of California Los Angeles, Los Angeles, CA
- Jenya Mamasakhlisov, PhD, Yerevan State University, Yerevan, Armenia
- Vanik Mkrtchian, PhD, Institute of Physics, National Academy of Sciences, Ashtarak, Armenia
- Jeremy Munday, PhD, California Institute of Technology, Pasadena, CA
- John F. Nagle, PhD, Carnegie-Mellon University, Pittsburgh, PA
- Richard Ratjer, BSc, Massachusetts Institute of Technology, Cambridge, MA
- Donald C. Rau, PhD, Program in Physical Biology, NICHD, Bethesda, MD
- Christopher Stanley, PhD, Center for Neutron Studies, NIST, Gaithersburg, MD
- Brian Todd, PhD, Program in Physical Biology, NICHD, Bethesda, MD
- Stephanie Tristram-Nagle, PhD, Carnegie-Mellon University, Pittsburgh, PA
- Thomas Zemb, PhD, CEA Saclay, Gif-sur-Yvette, France