Dynamics of macromolecular function and structure formation, equilibrium and non-equilibrium single molecule dynamics, pointillist and super-resolution nonlinear optical microscopies
University of Chicago, B.S., 1982.
California Institute of Technology, PhD, 1989.
National Science Foundation Postdoctoral Fellow, University of Chicago, 1989-1991; Postdoctoral Associate, 1991-1992.
University of Pennsylvania, Assistant Professor, 1992-1997.
The University of Chicago, Professor, 1997-.
Co-Director, Institute for Biophysical Dynamics, 1998-2002.
2006 John Simon Guggenheim Memorial Foundation fellowship.
2003 Fellow, American Physical Society.
1998 Invited Visiting Scholar, Irvine Materials Institute, University of California, Irvine, 1998.
1997 Alfred P. Sloan Fellow.
1996 Camille and Henry Dreyfus Teacher-Scholar Award.
1994-1996 Arnold and Mabel Beckman Young Investigator.
1993-1998 David and Lucile Packard Fellow.
1993-1998 National Science Foundation National Young Investigator.
Research in the Scherer group addresses a broad range of questions in three areas: function and transport in cellular biophysics, dynamics and excitations in driven nonequilibrium spatially-confined dense colloidal fluids, and optical trapping to assemble nano-plasmonic materials to realize long range coherence. The research is problem-oriented so that a wide range of proven and new experimental methods are applied or developed. Depending on the system and problem the measurements may be with femtosecond time resolution or the processes may take days. Each experimental problem has a corresponding theory component done either within the group or through collaborations. Our research has always involved development of experimental methods, including advances in ultrafast lasers and nonlinear spectroscopy, pointillist and nonlinear microscopy, and image analysis.
Cellular Biophysics: Function
How does a cell tell time? We study the cell cycle of the bacterium Caulobacter crescentus, primarily from a top-down perspective, by measuring the time required for the cell cycle to occur (division time), the growth of the cell and fluorescent fusion-protein reporters of the expression levels of specific proteins. We have developed an integrated optical microscopy and automated image analysis approach that allows measuring a thousand single cells for ~100 generations (so 105 single cell growth curves) over a weeklong experiment. The enormous amounts of data generated allow addressing fundamental questions of cell immortality and aging (senescence) with statistical significance. Stochastic simulations of network models are used to interpret the high level data. Amazingly, this biological system shows scaling behavior in its temperature-dependent dynamics, chemically controllable aging, and synchronization to external "clock-like" perturbations. We are currently investigating the applicability of linear response and whether the cell cycle obeys a fluctuation-dissipation relationship. Since we can control the state of the cell and drive it to new states, the bacterium allows addressing current frontier questions in the statistical mechanics of nonequlibrium steady-states and their dynamics.
Cellular Biophysics: Transport
How do objects move inside cells? We are studying the dynamics of insulin containing granule transport in beta cells, clusters thereof and in Islets of Langerhans with a longer view to whether the diabetic disease phenotype is related to transport. We have found a new statistics, which combines continuous time random walks with fractional Brownian motion, that describes the granule (vesicle) transport in these cells. We are extending these single granule particle tracking measurements to the dynamics of microtubules in vivo. This is a challenging issue from both the image analysis/tracking perspective and also establishing the correct mechanical description of their string-like motion. As for the bacterial system, we apply chemical and optogenetic perturbations to the cells to change the cell state to understand how transport, as a nonequilibrium process, is altered.
Nano-Photonics and Nano-Plasmonics
How can metal nanostructures control coherent light, and vice versa? Our recent focus has been on the plasmon transport properties of single noble metal nanowires, by simulation and experiment, and optical trapping methods for ordered assembly of nanoparticles and nanowires into active nanoscale plasmonic "devices". Plasmonic metal nanoparticles (e.g. spheroids, bipyramids, rods, wires, etc.) are strong light scatterers, so while they are a challenge to capture in an optical trap, they also readily exhibit another phenomenon termed optical binding. Optical binding involves the interference of incident and scattered light and thus creates modulated optical fields on the intermediate length scale (d ~ λ) and strong gradients in the near-field of the nanoparticles. These modulated fields, in turn, allow spatially registered trapping of other nanoparticles. We have now been able to create stable 2-D lattices of metal nanoparticles in solution that serve as a template for "co-trapping" of other smaller objects in the regions of large electric fields (and field gradients) in these metal nanoparticle lattices. As a demonstration we have co-trapped single semiconductor quantum dots into these lattices and have shown the close spatial correlation of the metal and semiconductor nanoparticles. This largely experimental and simulation effort is complemented by a theory project exploring the nonlinear optics of coupled plasmon-exciton systems.
Driven Dense Colloidal Fluids
How do we describe the excitations created by single colloids dragged through a dense colloidal fluid? Colloidal fluids are an interesting medium that allows visualizing phenomena that are analogous to molecular liquids yet can be tuned by density or confinement or interaction strength to (perhaps) allow insights into glassy or jammed materials. We create nonequilibrium perturbations in such fluids and use optical microscopy/imaging to measure the response(s) of the colloids that are the "bath." In addition to finding long range "dipolar" excitations that are evident in the ensemble responses elicited from dragging single colloids, we have also identified force-chain excitations and are relating the measured forces on the optically trapped particle to both the force-chain properties and those of the void volume (or hole) left in its wake. We are working on simulation approaches to understand the relation of these nonequilibrium excitations to spontaneous equilibrium fluctuations and thus to ascertain whether the nonequlibrium experimental approach is a way to create and measure what would be rare events. Finally, we are using on focused laser-induced tuning of local colloid interaction potentials to create active materials.
Guiding Spatial Arrangements of Ag Nanoparticles by Optical Binding Interactions in Shaped Light Fields. ACS Nano, accepted (2013).
Intracellular transport of insulin granules is a subordinated random walk. PNAS, accepted (2013).
Phase resetting reveals network dynamics underlying a bacterial cell cycle. PLoS Comput. Biol., 8, e1002778 (2012).
Three-Dimensional Optical Trapping and Manipulation of Single Silver Nanowires. Nano Lett., 12, 5155 (2012).
Structural Responses of Quasi-2D Colloid Fluids to Excitations Elicited by Nonequilibrium Perturbations. Phys. Rev. E, 86, 031403 (2012).
All-Optical Patterning of Au Nanoparticles on Surfaces Using Optical Traps. Nano Lett., 10, 4302 (2010).
Single-molecule non-equilibrium periodic Mg2+-concentration jump experiments reveal details of the early folding pathways of a large RNA. PNAS, 105, 6602 (2008).
Axis-dependent anisotropy in protein unfolding from integrated nonequilibrium single-molecule experiments, analysis, and simulation. PNAS, 104, 20799 (2007).
Field-Resolved Measurement of Reaction-Induced Spectral Densities by Polarizability Response Spectroscopy. J. Chem. Phys., 127, 184505 (2007).
Ultrafast Studies of Exciton Dynamics in Light Harvesting Dimers. Proc. SPIE, 3273, 244 (1998).