Bulletin of the American Physical Society
2005 APS March Meeting
Monday–Friday, March 21–25, 2005; Los Angeles, CA
Session U7: Nucleic Acid Translocation Through Nanopores |
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Sponsoring Units: DBP Chair: David Lubensky, Vrije University Room: LACC 408B |
Thursday, March 24, 2005 8:00AM - 8:36AM |
U7.00001: Silicon Nanopore Devices for DNA Translocation and Sequencing Studies Invited Speaker: In this talk, I will discuss the recent progress [1-3] in developing solid-state nanopore devices using silicon technology.~ We have demonstrated a novel technique for shaping nanopores in the range of 1-10 nm, using surface-tension-driven mass flow with single nanometer precision.~ This technique overcomes a major technical challenge in silicon technology. I will also discuss the current effort [3] in developing integrated nanopore silicon chips with electrically addressable nanopores. These devices are used for DNA translocation and sequencing studies.~ This work was done in collaboration with the group of Cees Dekker at TU-Delft with partial support from FOM and Guggenheim Foundation. The work at Brown was supported by NSF-NER and NSF-NIRT. \newline \newline [1] A.J. Storm, J.H. Chen, X.S. Ling, H. Zandbergen, and C. Dekker, ``Fabrication of Solid-State Nanopores with Single Nanometer Precision'', Nature Materials, 2, 537 (2003). \newline [2] A.J. Storm, J.H. Chen, X.S. Ling, H. Zandbergen, and C. Dekker, ``Electron-Beam-Induced Deformations of SiO2 Nanostructures'', Journal of Applied Physics (submitted, 2004). \newline [3] X.S. Ling, "Addressable nanopores and micropores" (patent pending). [Preview Abstract] |
Thursday, March 24, 2005 8:36AM - 9:12AM |
U7.00002: Anomalous dynamics of translocation Invited Speaker: We consider the passage of long polymers of length $N$ through a pore in a membrane. If the process is slow, it is in principle possible to focus on the dynamics of the number of monomers $s$ on one side of the membrane, assuming that the two segments are in equilibrium. The dynamics of $s(t)$ in such a limit is diffusive, with a mean translocation time scaling as $N^2$ in the absence of a force, and proportional to $N$ when a force is applied. We demonstrate that the assumption of equilibrium must break down for sufficiently long polymers (more easily when forced), and provide lower bounds for the translocation time by comparison to unimpeded motion of the polymer. These lower bounds exceed the time scales calculated on the basis of equilibrium, and point to anomalous (sub--diffusive) character of translocation dynamics. This is explicitly verified by numerical simulations of the unforced translocation of a self-avoiding polymer. Forced translocation times are shown to strongly depend on the method by which the force is applied. In particular, pulling the polymer by the end leads to much longer times than when a chemical potential difference is applied across the membrane. The bounds in these cases grow as $N^2$ and $N^{1+\nu}$, respectively, where $\nu$ is the exponent that relates the scaling of the radius of gyration to $N$. Our simulations demonstrate that the actual translocation times scale in the same manner as the bounds, although influenced by strong finite size effects which persist even for the longest polymers that we considered ($N=512$). [Preview Abstract] |
Thursday, March 24, 2005 9:12AM - 9:48AM |
U7.00003: Translocation and unzipping kinetics of DNA molecules using a nanopore Invited Speaker: We have developed a method to dynamically set the voltage applied across a phospholipid bilayer that contain a single $\alpha $-Hemolysin pore[1]. With this method the entry rate of single-stranded DNA or RNA molecules into the nanometer scale pore, and the voltage wave used to induce their unzipping rate, are independently controlled. Thus, hundreds of polynucleotides can be individually analyzed in a short period of time (a few minutes). We have used this method to characterized the unzipping kinetics of DNA hairpin molecules under fixed voltage amplitudes ($V)$, or steady voltage ramps ($\dot {V})$. We found that at high voltages ($V>30$ mV) or at high voltage ramps ($\dot {V}>5$ V/s) the unzipping process can be described by a single step kinetics model with negligible re-zipping probability. But at the low voltage (or voltage ramp) regime re-zipping probability must be included to account for our data[2]. A model that includes re-zipping is introduced and is used to fit our data at low and high voltages. From the fits we estimate the effective DNA charge inside the nanopore and the unzipping rate of the hairpins at the limit of zero force. 1. M. Bates, M. Burns, and A. Meller, Biophys. J. \textbf{84} (4), 2366 (2003). 2. J. Math\'{e}, H. Visram, V. Viasnoff, Y. Rabin and A. Meller, Biophys. J. \textbf{87 }(5), 3205 (2004). [Preview Abstract] |
Thursday, March 24, 2005 9:48AM - 10:24AM |
U7.00004: Simulation of Nucleic Acid Transport Through Carbon Nanotube Membranes Invited Speaker: We use molecular dynamics simulations to study the electrophoretic transport of single-stranded ribonucleic acid (RNA) molecules through 1.5-nm wide pores of carbon nanotube membranes. During a total simulation time of $\sim$800 ns, we observe $\sim$170 individual RNA translocation events at full atomic resolution of solvent, membrane, and RNA. By analyzing structure, thermodynamics, and kinetics, we identify key factors for the membrane transport of biopolymers. We find that RNA entry into the nanotube pores is controlled by conformational dynamics. Exit from the pores is strongly affected by hydrophobic attachment of RNA bases to the pore walls. Translocations with and without such hydrophobic binding result in slow and fast exit from the pores. We use a trap-diffusion model to describe the pore-blockage statistics obtained from the simulations and earlier experiments using an alpha-hemolysin pore. The rate of hydrophobic trapping depends only weakly on the applied electric field, whereas the rate of dissociation from the pore walls increases exponentially with the field. In the absence of an external electric field, RNA remains hydrophobically trapped in the membrane despite large entropic and energetic penalties for confining charged polymers inside nonpolar pores. We find that differences in RNA conformational flexibility and hydrophobicity result in sequence-dependent rates of translocation, a prerequisite for nanoscale separation devices. [Preview Abstract] |
Thursday, March 24, 2005 10:24AM - 11:00AM |
U7.00005: Kinetics of RNA translocation through a nanopore Invited Speaker: A nanopore is so small that only single-stranded but not double-stranded RNA molecules can pass through it. Thus, if an RNA molecule is driven through a nanopore its secondary structure has to be broken. This couples the dynamics of translocation through the pore to the dynamics of the secondary structure rearrangements of the molecule. Thus, translocation experiments of RNA molecules through nanopores give insight into secondary structure dynamics. In addition there are potential applications to the determination of RNA secondary structures and to the separation of RNA molecules according to their secondary structure features. We will present a theoretical framework in which to study this competition between translocation and structural dynamics. As a first application we study the crossover between a fast translocation regime in which the structure is easily destroyed and the translocation time is linear in the polymer length and a slow translocation regime in which the structure is in thermodynamic equilibrium at all times and the translocation time is dominated by the specific structural features. [Preview Abstract] |
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