Presented by The California Institute for Quantitative Biosciences (QB3) and the New York Academy of Sciences
Molecular Machines: Single-Molecule Tests of Nanoscale Cellular Functions
Posted December 14, 2007
Packed into every living cell is a factory's worth of molecular machines. Just billionths of a meter in size, these tiny devices perform the most basic and essential functions of life. Among their many duties is contraction of muscles; powering flagella; and reading and replicating genes.Molecular machines have been known to exist for many decades, but their small size has been a major barrier to their study. Recently, however, researchers have begun to gain the ability to manipulate the machines' individual components. Using single-molecule manipulation methods and techniques at the interface of mathematics, physics, and biology, they are beginning to understand the biomechanical principles that make nanomachines tick.
To provide an overview of these new approaches, and the natural nanodevices they are describing, the California Institute for Quantitative Biosciences (QB3) and the New York Academy of Sciences sponsored a symposium at the University of California, Berkeley, on October 20, 2007.
California Institute for Quantitative Biosciences (QB3)
A cooperative effort among UC Berkeley, UC Santa Cruz, and UC San Francisco dedicated to bringing quantitative sciences—mathematics, physics, chemistry, and engineering—to bear on biology.
International Society for Complexity, Information, and Design
See this entry in the ISCID encyclopedia for more background information on molecular machines.
Molecular Information Theory and the Theory of Molecular Machines
A site of lectures and resources curated by Tom Schneider at the NIH Center for Cancer Research Nanobiology Program.
Balzani V, Credi A, Venturi M. 2003. Molecular Devices and Machines: A Journey into the Nanoworld. Wiley-VCH, Weinheim, Germany.
Berg HC. 2003. E. coli in Motion. Springer-Verlag, New York.
Schliwa M, ed. 2003. Molecular Motors. Wiley-VCH, Weinheim, Germany.
Browne WR, Feringa BL. 2006. Making molecular machines work. Nature Nanotechnology 1: 25-35. Full Text
Altman DA, Sweeney HL, Spudich JA. 2004. The mechanism of myosin VI translocation and its load-induced anchoring. Cell 116: 737-749.
Ökten Z, Churchman LS, Rock RS, Spudich JA. 2004. Myosin VI walks hand-over-hand along actin. Nat. Struct. Mol. Biol. 11: 884-887.
Purcell TJ, Morris C, Spudich JA, Sweeney HL. 2002. Role of the lever arm in the progressive stepping of myosin V. Proc. Natl. Acad. Sci. USA 22: 14159-14164. Full Text
Rice SE, Purcell TJ, Spudich JA. 2003. Building and using optical traps to study properties of molecular motors. Methods Enzymol. 361: 112-133.
Gennerich A, Carter AP, Reck-Peterson SL, Vale RD. 2007. Force-induced bidirectional stepping of cytoplasmic dynein. Cell 131: 952-965.
Revyakin A, Ebright RH, Strick TR, Roberts JW. 2004. Promoter unwinding and promoter clearance by RNA polymerase: detection by single-molecule DNA nanomanipulation. Proc. Natl. Acad. Sci. USA 101: 4776-4780. Full Text
Antes I, Chandler D, Wang H, Oster G. 2003. The unbinding of ATP from F1-ATPase. Biophys. J. 85: 695–706. Full Text
Eide J, Chakraborty A, Oster G. 2006. Simple models for extracting mechanical work from the ATP hydrolysis cycle. Biophys. J. 90: 4281-4294. Full Text
Mogilner A, Wang H, Elston T, Oster G. 2002. Molecular motors: theory & experiment. In Fall C, Marland E, Wagner J, Tyson J, eds. Computational Cell Biology. Springer-Verlag, New York.
Oster G. 2002. Darwin's motors. Nature 417: 25.
Oster G, Wang H. 2003. Rotary protein motors. Trends Cell Biol. 13: 114-121.
Sun S, Dinner A, Chandler D, Oster G. 2003. Elastic energy storage in b-sheets with application to F1 ATPase. Eur. Biophys. J. 32: 676-683.
Wang H, Oster G. 2002. Ratchets, power strokes, and molecular motors. Applied Physics A 75: 315-323. (PDF, 314 KB) Full Text
Xing J, Liao J-C, Oster G. 2005. Making ATP. Proc. Natl. Acad. Sci. USA 102: 16539-16546. Full Text
Xing J, Wang H, Dimroth P, et al. 2004. Torque generation by the Fo motor of the sodium ATPase. Biophys. J. 87: 2148-2163. Full Text
Nakayama Y, Pauzauskie PJ, Radenovic A, et al. 2007. Tunable nanowire nonlinear optical probe. Nature 447: 1098-1101.
Pauzauskie PJ, Radenovic A, Trepagnier E, et al. 2006. Optical trapping and integration of semiconductor nanowire assemblies in water. Nat. Mater. 5: 97–101.
Reinhard B, Sheikholeslami S, Mastroianni A, et al. 2007. Use of plasmon coupling to reveal the dynamics of DNA bending and cleavage by single EcoRV restriction enzymes. Proc. Natl. Acad. Sci. USA 104: 2667-2672. Full Text
Sönnichsen C, Reinhard B, Liphardt J, Alivisatos AP. 2005. A molecular ruler based on plasmon coupling of single gold and silver nanoparticles. Nat. Biotechnol. 23: 741-745.
Walter JM, Greenfield D, Bustamante C, Liphardt J. 2007. Light-powering Escherichia coli with proteorhodopsin. Proc. Natl. Acad. Sci. USA 104: 2408–2412. Full Text
Berg HC. 2003. The rotary motor of bacterial flagella. Annu. Rev. Biochem. 72: 19-54.
Berg HC. 2000. Motile behavior of bacteria. Phys. Today 53: 24-29.
Turner L, Ryu WS, Berg HC. 2000. Real-time imaging of fluorescent flagellar filaments. J. Bacteriol. 182: 2793-2801. Full Text
James A. Spudich, PhD
James Spudich is professor of biochemistry and developmental biology at Stanford University School of Medicine. He is also cofounder and first director of Bio-X, an interdisciplinary program at Stanford. He is the Douglass M. and Nola Leishman Professor of Cardiovascular Disease, a member of the National Academy of Sciences, and cofounder of the Cytokinetics, Inc. The general research interest of his laboratory is the molecular basis of cell motility.
Arne Gennerich, PhD
Arne Gennerich is a postdoctoral fellow in the laboratory of Ron Vale at the University of California, Berkeley.
Andrey Revyakin, PhD
Andrey Revyakin is a postdoctoral fellow affiliated with the QB3 program at the University of California, Berkeley.
George Oster, PhD
George Oster is a professor in the Department of Molecular & Cellular Biology and the College of Natural Resources at the University of California, Berkeley. His research involves construction and testing of theoretical models of molecular, cellular, and developmental processes. Current projects include investigations into the basic physics and chemistry of protein motors, eukaryotic and prokaryotic cell motility, spatial pattern formation in eukaryotic and prokaryotic cells, and membrane geometry and protein organization.
Oster has been awarded numerous honors including election to the National Academy of Sciences and the American Academy of Arts and Sciences. He was a MacArthur Foundation Fellow and received the Weldon Memorial Prize from Oxford University. He received his PhD from Columbia University.
Howard Berg, PhD
Howard Berg is the Herchel Smith Professor of Physics and Professor of Molecular and Cellular Biology at Harvard University. His research group is trying to learn how the motor operating the bacterial flagellum works, the nature of the signal that controls the motor's direction of rotation, and how this signal is processed by the chemical sensory system. Berg received a PhD in physics from Harvard University.
Jan T. Liphardt, PhD
Jan Liphardt received a BA degree from Reed College in 1996, and a PhD from Cambridge University in 1999. After two years of postdoctoral work in the Physics and Chemistry Departments of UC Berkeley, he became the divisional fellow of the Physical Biosciences Division at Lawrence Berkeley Lab. He joined the physics faculty at Berkeley in 2004.
Liphardt's lab is developing novel instruments and probes for single molecule research, using nanopores fabricated in silicon nitride membranes to characterize biopolymers, and trying to build biobots, small (~100–300 nm) objects designed to exhibit interesting mechanical and biological properties.
Kathleen M. Wong
Kathleen M. Wong is a biologist and freelance science writer based in Oakland, California.