PHYSICAL FORCES ORGANIZING BIOMOLECULES
, Head, Section on Molecular Biophysics
Daniel Harries, PhD, Visiting Fellow1
Jason DeRouchey, PhD, Postdoctoral Fellow
Horia I. Petrache, PhD, Postdoctoral Fellow2
Xiangyun Qiu, PhD, Postdoctoral Fellow
Rudi Podgornik, PhD, Visiting Scientist
With a long-term goal to build a practical physics of biological material, we measure, characterize, and codify the interactions that govern the organization and self-assembly of different types of biological molecules. In part as a result of 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 with regard to their assembly but also, and more important, with respect to their suitability 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 different types 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; with polypeptides and polysaccharides in suspension; and with lipid/water liquid crystals. In all these systems, we observe the structure of packing and measure intermolecular interaction energies.
Van der Waals forces
While we recognize that van der Waals forces are the dominant interaction that coheres membranes and proteins, we are now systematically studying—in a collaboration with quantum physicists and biophysicists—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. This year, using the quantum-mechanical density functional theory solved for several carbon nanotubes, we computed the forces that cause the nanotubes to cohere and to serve as a substrate for many materials. It is remarkable that quantum chemistry combined with our expertise in macromolecular interactions is allowing us to see properties such as torque and the force between carbon nanotubes. We began our investigations by focusing on the elements of physical theory that relate the polarizability of materials to the fluctuations of charges within them. We have thus been able to design experiments that show how macromolecular organization responds to deliberate changes in solution properties. We demonstrated a tight coupling of the modern quantum theory of structured materials with experiments and measurements that revealed electromagnetic properties.
By teaming with other groups that measure absorption spectra, we formulated and computed van der Waals forces involving lipids, water, ions, and synthetic structures such as carbon nanotubes. The results have shown how charge fluctuation forces conferred by ions in solution can modify forces between lipid membranes. We measured those forces and computed van der Waals charge fluctuation forces in the same systems.
We also extended the Lifshitz theory of van der Waals interactions in stratified media such as lipid multilamellar systems, thereby enabling us to compute forces between bodies with extended interfaces ranging from the practical—the composite media of electric insulators—to the biological—the action of extended polymer layers on biological membranes.
Parsegian VA. Van der Waals Forces: a Handbook for Biologists, Chemists, Engineers, and Physicists. Cambridge University Press, 2006.
Podgornik R, French RH, Parsegian VA. Nonadditivity in van der Waals interactions within multilayers. J Chem Phys 2006;124:044709.
Rajter RF, Podgornik R, Parsegian VA, French RH, Ching WY. van der Waals-London dispersion interactions for optically anisotropic cylinders: metallic and semiconducting single-wall carbon nanotubes. Phys Rev B 2007;76:045417.
Veble G, Podgornik R. Comparison of density functional theory and field approaches to van der Waals interactions in plan parallel geometry. Phys Rev B 2007;75:155102.
Veble G, Podgornik R. The boundary element approach to Van der Waals interactions. Eur Phys J E Soft Matter 2007;23:275-9.
Molecular assembly in vitro and in vivo
We have developed new theories and new methods of macromolecular organization by 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. In particular, we observed DNA under the osmotic stress of large polymers or confined within the hard walls of a virus capsid.
The osmotic action of small solutes controls a remarkable number of cellular processes, including the gating of ionic channels and specific versus non-specific DNA–protein interactions regulating gene expression. Osmotic sensing at the molecular level can probe the forces acting between and within macromolecules. By varying the salt or neutral “osmolyte” concentration in the bathing solution, we control osmotic pressure.
Most recently, we observed the ejection of DNA from capsids subjected to different salt conditions. Expansive pressures, which are responsible for the initial ejection of DNA, can vary up to many tens of atmospheres. Ionic conditions, in turn, may vary these pressures. An unrecognized feature of many viruses is that ionic conditions can penetrate a virus and even modify the expansive force within it. At one extreme, DNA in simple salts is under great pressure to expand and be ejected from the capsid; under other conditions, where DNA-condensing ions can enter the capsid, DNA may be under no expansive pressure. We have started to measure the motion of DNA within capsids subjected to different ionic conditions to see how ionic surroundings might control ejection. Whether these manipulations ultimately affect viral infectivity is a worthwhile and exciting question for investigation.
Evilevitch A, Fang LT, Yoffe A, Castelnovo M, Rau D, Parsegian VA, Knobler CM, Gelbart WM. Effects of salt concentration and bending energy on the extent of ejection of phage genomes. Biophys J 2007 [E-pub ahead of print].
Manna F, Lorman V, Podgornik R, Žekš B. Screwlike order, macroscopic chirality, and elastic distortions in high-density DNA mesophases. Phys Rev E 2007;75:030901R.
Podgornik R. Interactions and conformational fluctuations in DNA arrays. In: Poon V, Wilson CK, Andelman D, eds. Soft Condensed Matter Physics in Molecular and Cell Biology. Taylor & Francis, 2006;181-99.
Tomic S, Dolanski-Babic S, Krca S, Ivanovic D, Griparic L, Podgornik R. Dielectric relaxation of DNA aqueous solutions. Phys Rev E 2007;75:021905.
Tomic S, Vuletic T, Dolanski Babic S, Krca S, Ivankovic D, Griparic L, Podgornik R. Screening and fundamental length scales in semidilute Na-DNA aqueous solutions. Phys Rev Letts 2006;97:098303.
Publications Related to Other Work
Gondre-Lewis MC, Petrache HI, Wassif CA, Harries D, Parsegian A, Porter FD, Loh YP. Abnormal sterols in cholesterol-deficiency diseases cause secretory granule malformation and decreased membrane curvature. J Cell Sci 2006;119:1876-85.
Harries D, Podgornik R, Parsegian VA, Mar-Or E, Andelman D. Ion induced lamellar-lamellar phase transition in charged surfactant systems. J Chem Phys 2006;124:224702.
Holecek N, Sirok B, Hocevar M, Podgornik R, Grudnik R. Reducing the noise emitted from a domestic clothes-drying machine. Noise Control Eng J 2006;54:137-45.
Kanduč M, Podgornik R. Electrostatic image effects for counterions between charged planar walls. Eur Phys J E Soft Matter 2007;23:265-74.
Petrache HI, Tristram-Nagle S, Harries D, Kucerka N, Nagle JF, Parsegian VA. Swelling of phospholipids by monovalent salt. J Lipid Res 2006;47:302-9.
Petrache HI, Zemb T, Belloni L, Parsegian VA. Salt screening and specific ion adsorption determine neutral-lipid membrane interactions. Proc Natl Acad Sci USA 2006;103:7982-7.
Podgornik R. DNA off the Hooke. Nat Nanotechnol 2006;1:100-1.
Podgornik R, Licer M. Polyelectrolyte bridging interactions between charged macromolecules. Curr Op Coll Interf Sci 2006;11:273-9.
Podgornik R, Najii A. Electrostatic disorder-induced interactions in inhomogeneous dielectrics. Europhys Letts 2006;74:712-8.
Slosar A, Podgornik R. On the connected-charges Thomson problem. Europhys Letts 2006;75:631-7.
van Benthem K, Tan G, French RH, DeNoyer LK, Podgornik R, Parsegian VA. Graded Interface Models for more accurate determination of van-der-Waals ? London Dispersion interactions across grain boundaries. Phys Rev B 2006;74:205110.
1 now Hebrew University, Jerusalem
2 now Purdue University, Indianapolis
COLLABORATORS
David Andelman, PhD, Tel Aviv University, Tel Aviv, Israel
Sergey Bezrukov, PhD, Program in Physical Biology, NICHD, Bethesda, MD
W. Craig Carter, PhD, Massachusetts Institute of Technology, 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 Gurnev, PhD, Program in Physical Biology, NICHD, Bethesda, MD
Per Lyngs Hansen, PhD, Syddansk Universitet, Odense, Denmark
Charles Knobler, PhD, University of California Los Angeles, Los Angeles, CA
Jenya Mamasaklisov, PhD, Yerevan State University, Yerevan, Armenia
Vanik Mkrtchian, PhD, Institute of Physics, National Academy of Sciences, Ashtarak, Armenia
John F. Nagle, PhD, Carnegie-Mellon University, Pittsburgh, PA
Richard Rajter, BSc, Massachusetts Institute of Technology, Cambridge, MA
Donald Rau, PhD, Program in Physical Biology, NICHD, Bethesda, MD
Jonathan Sachs, PhD, NIST, Gaithersburg, 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
For further information, contact parsegi@mail.nih.gov.
