Bulletin of the American Physical Society
APS March Meeting 2013
Volume 58, Number 1
Monday–Friday, March 18–22, 2013; Baltimore, Maryland
Session F4: Industrial Physics Forum: Frontiers in Biophysics |
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Sponsoring Units: FIAP Chair: James Hollenhorst, Agilent Technologies Room: Ballroom IV |
Tuesday, March 19, 2013 8:00AM - 8:36AM |
F4.00001: Biophysical Variables Which Are Available from Single-Molecule Optical Studies Invited Speaker: W.E. Moerner Since the first optical detection and spectroscopy of a single molecule in a condensed phase host in 1989, a wealth of new information has been obtained from time-dependent measurements and single-molecule probability distributions. When single-molecule imaging is combined with active control of the emitter concentration, enhanced spatial resolution well beyond the optical diffraction limit can be obtained for a wide array of biophysical structures in cells. Single-molecule emitters also provide precise and accurate 3D position as well as dipole moment orientation when combined with Fourier plane processing. Examples here include the implementation of a double-helix point spread function for 3D position information (Backlund, Lew et al. PNAS (2012)), and the creation of a quadrated pupil response to sense emission dipole orientations (Backer et al. submitted 2012). If high-resolution spatial information is not needed, a machine called the Anti-Brownian ELectrokinetic (ABEL) trap provides real-time suppression of Brownian motion for single molecules in solution for extended analysis of dynamical state changes (Wang et al. Acc. Chem. Res. (2012)). With proper design of reporter fluorophore, individual electron transfer events to a single Cu atom in a redox enzyme may be sensed under turnover conditions (Goldsmith et al. PNAS (2011)). Optical counting of fluorescent ATP nucleotides on a multisubunit enzyme provides measurement of ATP number distributions, which can be used to generate a new window into enzyme cooperativity devoid of ensemble averaging (Jiang et al PNAS (2011)). With advanced control system design of feedback to enable optimal trapping performance, the ABEL trap also allows direct, simultaneous measurement of three variables: brightness, excited state lifetime, and emission spectrum, for objects as small as individual $\sim$1-2 nm sized fluorophores in solution (Wang et al. JPCB (in press 2013)). These examples illustrate some of the wide variety of physical variables which may now be measured for single molecules in a various condensed phase environments ranging from aqueous solutions to living cells. [Preview Abstract] |
Tuesday, March 19, 2013 8:36AM - 9:12AM |
F4.00002: Accounting for conformational flexibility when targeting proteins Invited Speaker: Sara Nichols Molecular simulation techniques are well-established tools for understanding protein motion and complementing experimental observations. Molecular conformations from such simulations provide insight into receptor flexibility, particularly with respect to the binding of activity-modulating molecules, such as drugs. With the ultimate goal of predicting and designing these favorable interactions, incorporating information about flexibility can enhance structure-based drug design. While modeling all receptor degrees of freedom can be challenging due to conformational space sampling restrictions, advances in computing technology, hybrid and hierarchical protocol, as well as enhanced sampling algorithms are making an impact now, and will continue to do so in the future. An overview of these topics and applications to specific therapeutic targets will be presented. [Preview Abstract] |
Tuesday, March 19, 2013 9:12AM - 9:48AM |
F4.00003: Changing Chasses and Inventing Elements: Developing a Combined Systems Biology and Engineering Approach to Designing Complex Function in Cells Invited Speaker: Adam Arkin To meet the goal of creating reliable, predictable, efficient, and transparent methods to harness cellular capabilities for human benefit, it is necessary both to have standard libraries of elements from which useful pathways can be constructed and an understanding of the how host physiology and the environment impacts the functioning of these heterologous circuits. We show how variations in cellular and environmental context affect the operation of the basic central dogma functions underlying gene expression. Then we describe progress on creating a complete, scalable, and relatively homogeneous and designable sets of part families that can control central dogma function predictably in the face of varying configurations, genetic contexts, and environments. We show the challenges that arise in attempting this in applications such as a tumor destroying bacteria. [Preview Abstract] |
Tuesday, March 19, 2013 9:48AM - 10:24AM |
F4.00004: Frontiers of Biophysics: Single Molecule and Single Cell Sensing with Nanomechanical Systems Invited Speaker: Michael Roukes Nanoelectromechanical systems (NEMS) resonators can detect inertial mass with exceptional sensitivity. We have used NEMS devices to realize a new method for single-molecule mass spectrometry. In our first-generation approach, mass spectra from several hundred adsorption events were assembled into mass spectra using statistical analysis. Our second-generation approach now enables NEMS-based mass spectrometry (MS) in real time: as each molecule in the sample adsorbs upon the NEMS resonator, its mass and position-of-adsorption are determined by continuously tracking two driven vibrational modes of the device. We demonstrate the potential of this method by analyzing individual IgM antibody complexes and other biological analytes in real-time. NEMS-MS is a unique and promising new form of mass spectrometry: it can resolve neutral species, provides resolving power that increases markedly for very large masses, is readily scalable to millions of channels, and is and producible \textit{en masse} by methods from the semiconductor industry for very-large-scale integration. [Preview Abstract] |
Tuesday, March 19, 2013 10:24AM - 11:00AM |
F4.00005: Cytometry and Atomic Mass Spectrometry Converge in Single Cell Deep Profiling of the Human Immune System Invited Speaker: Scott Tanner Mass cytometry addresses the challenges of polychromatic flow cytometry by capitalizing on the analytical benefits of atomic mass spectrometry. Fluorescence flow cytometry has helped to define the cell subsets of the immune system. The addition of intracellular staining facilitated examination of signaling networks and, recently stratification of patients correlated with clinical outcome. However, the potential for further advances has been stymied by the physical and spectral limitations of fluorophores. This technical barrier has been broached by replacing fluorophores with heavy metal isotopes, and optical detection with atomic mass spectrometry. Antibodies raised against phenotypic and functional proteins are tagged with polymers that are labeled with the transition metal isotopes. More than 30 lanthanide isotopes, complemented by noble metals, permit the immunological recognition of more than 40 (and conceptually up to 100) proteins in single cells simultaneously. Individual cells are injected at nearly 1 kHz into an Inductively Coupled Plasma where the cells are vaporized, atomized and ionized. The reporting ions within the vaporization cloud of each cell are extracted, separated and counted by a time-of-flight mass spectrometer. The data output is a massively multivariate signature of each cell. Already the technology has offered dramatic new insights into the operation and function of the human hematopoietic hierarchy, shown novel application for the screening and mechanistic understanding of drug candidates, and foresees improved prognostic and diagnostic application in the clinic. We will report on our work, and the work of others, in profiling the signaling and functional responses of the suite of cell populations in human bone marrow, the revealing of unappreciated levels of organization in virus-specific memory T cell compartments, and massively multiplexed single-cell kinase inhibitor profiling. [Preview Abstract] |
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