Assistant Professor of Physics
Ph.D., University of Chicago
B.A., UC Berkeley
Member of: Institute of Molecular Biology
174 Willamette Hall
Lab: 171 Willamette Hall
Research Interests
We construct experiments to explore a variety of topics in Biophysics and Soft Condensed Matter Physics. Throughout these fields, we encounter systems in which individually simple molecular components interact to give rise to complex, dynamic phenomena.
Membrane Biophysics membrane
Cellular membranes are remarkable materials -- flexible, two-dimensional fluids at which mobile, nanometer-scale proteins play reactive and structural roles (see illustration). How do the material properties of membranes -- their rigidity, the mobility of lipids and proteins, their various phase transitions -- contribute to their function and their ability to spatially organize? How do the unusual structures and compositions of the membranes of various organisms contribute to their survival? 
The biophysics of tuberculosis -- Mycobacterial membrane mimics
Tuberculosis infects about one-third of the human population and kills two million people every year. It is a remarkably robust organism, capable for example of surviving for months under conditions of extreme dehydration. Mycobacteria, which include the species that cause tuberculosis and leprosy, have membranes that are unusual in both their structure and their composition. To examine the role the membrane may play in conferring to the bacteria their remarkable physical properties, we have created artificial solid-supported membranes that mimic these mycobacterial envelopes (see schematic, below). These mimics allow new sorts of quantitative examinations of their physical properties by enabling control of membrane composition and quantitative assays of membrane behavior. We have recently discovered that a certain glycolipid present in all the mycobacteria has the ability to make membranes resistant to dehydration. Moreover, even as a minority component, this mycobacterial lipid protects membranes against desiccation. This is the first dehydration-resistant lipid ever discovered. For details, see our recent paper (Harland et al., 2008) .
Present work involves the development of still more sophisticated mycobacterial mimics as well as the creation of new materials that mimic the mycobacterial envelope for technological ends.
Membrane fluidity and membrane rigidity
We are developing new methods to probe the basic mechanical properties of membranes: their two-dimensional fluidity and their bending rigidity. Our approaches are based on new optical techniques, involving interferometry to measure nanometer-scale membrane deformations, and microrheological tools to measure molecular mobility. Though 2D mobility is a fundamentally important attribute of biological membranes, its physical underpinnings are remarkably poorly understood.
Membrane-membrane interactions
Inspired by striking examples of spatial organization found at certain cell-cell junctions, we construct bilayer-bilayer junctions to unravel some of the relevant mechanics. For example, the picture above is from a fluorescence image of antibodies bound to a lipid membrane, after a second membrane comes into contact. Before the membrane-membrane junction is formed by the introduction of the second bilayer, the antibodies are uniformly distributed. When the junction forms, remarkable patterns emerge. The antibodies form "leopard spots" of high and low density (bright and dark in the image below). These protein patterns can be used to extract structural information about the proteins and the lipid bilayers themselves, as well as serving as a reminder that even simple situations can produce complex patterns.
False-color fluorescence micrograph of antibodies at a membrane-membrane junction. The length-scale of the high- and low- density zones is related to the membrane rigidity and the protein mobility. Image width = 50 microns.
Curvature and lipid phase transitions
Despite being fluid, cellular membranes are spatially non-uniform, an attribute of importance for the functioning of cell-signaling networks. Phase separation into chemically distinct domains (e.g. of "white" and "black" lipids in the sketch below) is believed to play a large role in driving membrane heterogeneity, but the means by which phase separation is controlled remain unclear. We have recently shown, using microfabricated materials to impart specific curvature profiles onto lipid membranes, that curvature is sufficient to control the spatial organization of phase-separated domains. phase separation
Macromolecular structure
We are developing new methods for examining the mechanical properties of proteins and other macromolecules. These include investigations of the role of glycosylation (the presence of sugar groups) on molecular rigidity, the mobility of protein domains about "hinge" regions, and the orientation of surface-anchored DNA.
Colloidal assemblies + optical traps
Can bio-membranes be used to create new, non-biological materials? We're interesting in using membrane-functionalization of microparticles (see illustration) as a means of controlling interparticle interactions and generating complex self-organized assemblies.
membrane-functionalized particle.
To reach these aims, we have invented new types of optical traps (see papers, Tietjen et al., 2008) that facilitate measurements of colloidal interactions and are developing additional approaches that will allow these composite particles to self-assemble into crystalline lattices.
We are also interested other types of soft condensed matter, such as polymer gels, colloidal dispersions, and emulsions -- especially in contexts in which their structural properties can influence and be influenced by various bio-molecules. To explore the above-mentioned topics, we use and also develop a variety of advanced optical microscopy techniques. These include methods based on optical interference that provide nanometer-scale probes of system structure. (See papers, Groves et al., 2008, for a recent review.)
Selected Publications
Gregory T. Tietjen, Yupeng Kong, and Raghuveer Parthasarathy "An efficient method for the creation of tunable optical line traps via control of gradient and scattering forces," Opt. Express 16: 10341-10348 (2008) [Link]
Christopher W. Harland, David Rabuka, Carolyn R. Bertozzi, and Raghuveer Parthasarathy. The M. tuberculosis virulence factor trehalose dimycolate imparts desiccation resistance to model mycobacterial membranes. Biophys. J. 94: 4718-4724 (2008). [Link]
Jay T. Groves, Raghuveer Parthasarathy, and Martin B. Forstner,"Fluorescence Imaging of Membrane Dynamics," Annu. Rev. Biomed. Eng. 10: 311-338 (2008). [Link]
Raghuveer Parthasarathy, David Rabuka, Carolyn Bertozzi, and Jay T. Groves,"Molecular Orientation of Membrane-Anchored Mucin Glycoprotein Mimics, J. Phys. Chem. B, 111: 12133-12135 (2007). [ACS]
David Rabuka, Raghuveer Parthasarathy, Goo Soo Lee, Xing Chen, Jay T. Groves, and Carolyn Bertozzi,"Hierarchical Assembly of Model Cell Surfaces: Synthesis of Mucin Mimetic Polymers and Their Display on Supported Bilayers," J. Amer. Chem. Soc., 129: 5462-5471 (2007). [ACS]
Raghuveer Parthasarathy and Jay T. Groves,"Curvature and spatial organization in biological membranes,” Soft Matter, 3: 24-33 (2007). [Link to Soft Matter] [ Journal Cover ]
Raghuveer Parthasarathy, Cheng-han Yu, and Jay T. Groves, “Curvature modulated phase separation in lipid bilayer membranes,” Langmuir, 22: 5095-5099 (2006). [ACS]
Raghuveer Parthasarathy and Jay T. Groves, “Coupled membrane fluctuations and protein mobility in supported intermembrane junctions,” J. Phys. Chem. B, 110: 8513-8516 (2006). [ACS]
Raghuveer Parthasarathy, Paul A. Cripe, and Jay T. Groves, “Electrostatically Driven Spatial Patterns in Lipid Membrane Composition,” Phys. Rev. Lett. 95: 048101 (2005). [PubMed]
Raghuveer Parthasarathy and Jay T. Groves, “Protein Patterns at Lipid Bilayer Junctions,” Proc. Natl. Acad. Sci. 101: 12798-12803 (2004). [PubMed]
Raghuveer Parthasarathy and Jay T. Groves, “Optical techniques for imaging membrane topography,” Cell Biochem. Biophys. 41: 391-414 (2004). [PubMed]
Raghuveer Parthasarathy, Bryan L. Jackson, Thomas J. Lowery, Amy P. Wong, and Jay T. Groves, “Nonequilibrium Adhesion Patterns at Lipid Bilayer Junctions,” J. Phys. Chem. B 108: 649-657 (2004). [ACS]
Raghuveer Parthasarathy, Xiao-Min Lin, Klara Elteto, T. F. Rosenbaum, and Heinrich M. Jaeger, “Percolating through Networks of Random Thresholds: Finite Temperature Electron Tunneling in Metal Nanocrystal Arrays,” Phys. Rev. Lett. 92: 076801 (2004).
Xiao-Min Lin, Raghuveer Parthasarathy, and Heinrich M. Jaeger, “Nanocrystal Arrays: Self-assembly and physical properties,” in the Dekker Encoclyopedia of Nanoscience and Nanotechnology, ed. J.A. Schwarz, C.I. Contescu, K. Putyera (Dekker, 2004).
Thomas Scheibel, Raghuveer Parthasarathy, George Sawicki, Xiao-Min Lin, Heinrich Jaeger, and Susan L. Lindquist, “Conducting nanowires built by controlled self-assembly of amyloid fibers and selective metal deposition,” Proc. Natl. Acad. Sci. 100: 4527-4532 (2003). [PNAS]
Raghuveer Parthasarathy, Xiao-Min Lin, and Heinrich M. Jaeger,
“Electronic transport in metal
nanocrystal arrays: the effect of structural disorder on scaling behavior,”
Phys. Rev. Lett. 87: 186807 (2001).
Xiao-Min Lin, Raghuveer Parthasarathy, and Heinrich M. Jaeger, “Direct patterning of self-assembled nanocrystal monolayers by electron beams,” Appl. Phys. Lett. 78: 1915-1917 (2001). [Link]
H. M. Rønnow, R. Parthasarathy, J. Jensen, G. Aeppli, T. F. Rosenbaum, and D. F. McMorrow, “Quantum phase transition of a magnet in a spin bath,” Science 308: 389-392 (2005). [Link]
S. Ghosh, R. Parthasarathy, T. F. Rosenbaum, and G. Aeppli, “Coherent spin oscillations in a disordered magnet,” Science 296: 2195-2198 (2002). [Link]
S. Anders, R. Parthasarathy, H. M. Jaeger, P. Guptasarma, D. G. Hinks, and R. van Veen, “Dynamics of the second peak in the magnetization of Bi2Sr2CaCu2O8 crystals,” Phys. Rev. B 58: 6639-6644 (1998).
D. H. Cobden, G. Pilling, R. Parthasarathy, P. L. McEuen, I. M. Castleton, E. H. Linfield, D. A. Ritchie, and G. A. C. Jones, “Current flow past an etched barrier: field emission from a two-dimensional electron gas,” Europhys. Lett. 41: 327-332 (1998).
R. Parthasarathy, C. Franck, R. Treffers,
D. Cudaback, C. Heiles, C. Hancox, and R. Millan, “A rooftop radio
observatory: an undergraduate telescope system at the University of
California at Berkeley,” Am. J. Phys. 66: 768-771 (1998).
297 Klamath Hall Hall