Bulletin of the American Physical Society
APS March Meeting 2017
Volume 62, Number 4
Monday–Friday, March 13–17, 2017; New Orleans, Louisiana
Session L4: Physics of Genome Organization: from DNA to Chromatin IIFocus
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Sponsoring Units: DBIO GSOFT Chair: Leonid Mirny, MIT Room: 263 |
Wednesday, March 15, 2017 11:15AM - 11:51AM |
L4.00001: How to read and write mechanical information in DNA molecules Invited Speaker: Helmut Schiessel In this talk I will show that DNA molecules contain another layer of information on top of the classical genetic information. This different type of information is of mechanical nature and guides the folding of DNA molecules inside cells. With the help of a new Monte Carlo technique, the Mutation Monte Carlo method \footnote{B. Eslami-Mossallam, R. D. Schram, M. Tompitak, J. van Noort, H. Schiessel, \textbf{PLoS ONE} 11, e0156905 (2016)}, we demonstrate that the two layers of information can be multiplexed (as one can have two phone conversations on the same wire). For instance, we can guide on top of genes with single base-pair precision the packaging of DNA into nucleosomes. Finally, we study the mechanical properties of DNA molecules belonging to organisms all across the tree of life. From this we learn that in multicellular organisms the stiffness of DNA around transcription start sites differs dramatically from that of unicellular life. The reason for this difference is surprising. [Preview Abstract] |
Wednesday, March 15, 2017 11:51AM - 12:03PM |
L4.00002: Role of Nucleoid Associated Proteins in Stabilizing Supercoils Katelyn Dahlke, Charles Sing Nucleoid associated proteins (NAPs) play an important role in prokaryotic cells by manipulating the shape and structure of the DNA. These NAPs act by bending or twisting DNA, and there are indications that NAPs bind preferentially to DNA that is already bent or twisted. We hypothesize that these binding behaviors strongly impact the stability and structure of DNA. We use coarse-grained simulation of NAPs and DNA that allow us to achieve the time and length scales where DNA ‘supercoiling’ occurs. Supercoils are twist-induced structures that are the result of relaxing highly-twisted DNA by inducing higher degrees of bending and writhe. We are able to reproduce experimental observations, such as the extension of a DNA molecule as a function of force, linking number, and NAP concentration. Building upon these test cases, we allow the binding and unbinding energy of the simulated NAPs to be a function of the bending angle of the DNA at the site of binding ($\Delta E_B (\theta)$). Consequently, NAPs localize along the contour of the supercoil, and this binding preference is capable of stabilizing supercoils that form within the nucleoid. [Preview Abstract] |
Wednesday, March 15, 2017 12:03PM - 12:15PM |
L4.00003: Torque and buckling in stretched intertwined double-helix DNAs Sumitabha Brahmachari, John F. Marko We present a statistical mechanical model for the mechanical behavior of two intertwined DNAs under applied force, with a focus on their torque and extension as a function of their linking number (catenation). Our model agrees favorably with available experimental data and predicts a torque that grows non-linearly with linking number, distinct from what is observed in individual twisted double-helix DNA. We find that buckling occurs near the catenation where experiments have observed a change in the slope of the extension versus catenation curves and that the buckled state corresponds to a coexistence of many small plectoneme domains. We predict a discontinuity in extension at the buckling transition corresponding to nucleation of the first plectoneme domain. We also find that buckling occurs for lower catenation at lower salt; the opposite trend is observed for single supercoiled double helices. [Preview Abstract] |
Wednesday, March 15, 2017 12:15PM - 12:27PM |
L4.00004: Dynamic Coupling among Protein Binding, Sliding, and DNA Bending Revealed by Molecular Dynamics Cheng Tan, Tsuyoshi Terakawa, Shoji Takada Protein binding to DNA changes the DNA’s structure, and altered DNA structure can in turn modulate the dynamics of protein binding. This mutual dependency is crucial for genome organization, but poorly understood. Here we investigated dynamic couplings among protein binding to DNA, protein sliding on DNA, and DNA bending by applying coarse-grained simulations to the bacterial architectural protein HU and 14 other DNA-binding proteins. First, we showed that the simulated HU exhibits a strong preference for DNA gap, consistent with biochemical experiments. The high affinity was attributed to a local DNA bend. The long-time dynamic analysis revealed that HU sliding is associated with the movement of the local DNA bending. Deciphering single sliding steps, we found the coupling between HU sliding and DNA bending is akin to cation transfer on DNA and can be viewed as a protein version of polaron-like sliding. Interestingly, on shorter time scales, HU paused when the DNA was highly bent and escaped from pause once the DNA spontaneously returned to a less bent structure. With 14 other proteins, we explored the generality and versatility of the dynamic coupling and found that 6 assayed proteins exhibit the polaron-like sliding.\footnote{C. Tan \textit{et al., JACS} 2016, 138, 8512.} [Preview Abstract] |
Wednesday, March 15, 2017 12:27PM - 12:39PM |
L4.00005: A mean-field internal tension accounts for the elasticity of ssDNA Omar A. Saleh Single-stranded DNA (ssDNA) is a highly-charged biopolymer whose flexibility permits strong interactions between monomers well-spaced along the backbone. The configuration of any given subunit of the chain is thus sensitive to the position of many monomers, creating a complex set of interactions that have resisted simple conceptualization. I will discuss progress in understanding ssDNA configuration using a classic mean-field approach, in which long-range interactions are approximated by an intrinsic tension that locally straightens the chain. This approach works surprisingly well in describing two sets of single-molecule stretching data: the salt-dependent elasticity of ssDNA (in which the internal tension arises from electrostatic repulsions between monomers), and the elastic response of an ssDNA backbone with grafted side chains (in which the internal tension arises from steric repulsions between side chains). [Preview Abstract] |
Wednesday, March 15, 2017 12:39PM - 12:51PM |
L4.00006: How deforming DNA conformations can yield better translocation statistics in the highly-driven limit. David Sean, Hendrick W. de Haan, Gary W. Slater DNA translocation through solid-state nanopores typically occurs over a timescale much shorter than the DNA relaxation time: the process is highly out of equilibrium. Coarse-grained Langevin Dynamics simulations in such driving conditions demonstrate that the translocation times are significantly dependent upon the initial polymer conformations. In addition to thermal noise, the range of the initial polymer conformations contribute to the width of the translocation time distribution. By deforming the polymer prior to—and during—the translocation process, we study ways in which the range of initial conformations can be reduced as a means to produce translocation events with a tighter time distribution. To achieve this, we focus on using geometrical confinement as well as via the use of additional external forces applied on the polymer ends. We show how the translocation time distribution is affected by both the amplitude of thermal noise and the degree of polymer deformation when we apply external constraints. Different confining geometries can be chosen to achieve i) translocation events which take a longer time period; ii) translocation time distributions with a smaller variance; and/or iii) mean translocation rates that are much more constant throughout the process. [Preview Abstract] |
Wednesday, March 15, 2017 12:51PM - 1:27PM |
L4.00007: Abstract Withdrawn Invited Speaker:
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Wednesday, March 15, 2017 1:27PM - 1:39PM |
L4.00008: DNA dynamics squeezed inside a nano-channel with a sliding gasket Tyler Campbell, Aniket Bhattacharya, Walter Reisner We study transients and steady states of a DNA inside a rectangular nano-channel squeezed by a sliding gasket$^{1,2,3}$. We carry out Brownian dynamics (BD) simulation for a DNA modeled as a semi-flexible polymer characterized by its contour length $L$ and the persistence length $\ell_p$. Specifically we study the evolution of one dimensional concentration profile $c(x,t)$ and the chain extension $R$ along the channel axis ($x$-axis) during both the contracting as well as the retracting phases as a function of the velocity of the nano-dozer, both in steady states and in transients as a function of the dimensionless parameter $\ell_p/D$, where $D$ is the channel diameter. Consistent with the equilibrium conformations in the form of de Gennes blobs ($\ell_p/D \sim 1$) and Odijk deflection lengths ($\ell_p/D \gg 1$), our systematic studies of the non-equilibrium dynamics of the squeezed DNA reveal interesting features which could be rationalized with their corresponding equilibrium conformations. \\ $^1$ A. Khorshid et al., Phys. Rev. Lett, {\bf 113}, 268104 (2014)).\\ $^2$ A. Khorshid, S. Amin, Z. Zhang, T. Sakaue, and W. Reisner, Macromolecules {\bf 49}, 1933 (2016).\\ $^3$ A. Huang, W. Reisner,and A. Bhattacharya, Polymers {\bf 8}, 352 (2016). [Preview Abstract] |
Wednesday, March 15, 2017 1:39PM - 1:51PM |
L4.00009: Magnetic Actuation of Self-Assembled DNA Origami Systems S. Lauback, K. Mattioli, A. E. Marras, M. Armstrong, C. Miller, C. E. Castro, R. Sooryakumar Central to advancing DNA nanotechnology is the ability to actuate or reconfigure structures in real time. Such actuation is achieved primarily by DNA strand displacement -- a relatively slow process (minutes) that transforms the structure between two distinct configurations. In this study it is shown that, through use of superparamagnetic beads, DNA constructs can not only be actuated within seconds but their reconfiguration is achieved in a continuous range of finely tuned steps. Three systems -- a rod, rotor, and hinge -- are built using DNA origami components. A stiff micron-scale DNA rod is constructed by attaching thick DNA origami bundles end-to-end. In this rod system, one end is attached to the surface, while in the case of the rotor the rod is attached in the center to a nano-platform fixed to the surface. The hinge system is created using two DNA rods attached to the arms of a nano-hinge forming a pair of micron length handles in which one is fixed to the surface while the other is free to rotate. In all three systems, the rods are functionalized with magnetic beads to enable their actuation with weak external magnetic fields. These results are vital to establish rapid real-time manipulation of DNA constructs. [Preview Abstract] |
Wednesday, March 15, 2017 1:51PM - 2:03PM |
L4.00010: Mechano-genetic DNA hydrogels as a simple, reconstituted model to probe the effect of active fluctuations on gene transcription. Dan Nguyen, Omar Saleh Active fluctuations -- non-directed fluctuations attributable, not to thermal energy, but to non-equilibrium processes -- are thought to influence biology by increasing the diffusive motion of biomolecules. Dense DNA regions within cells (i.e. chromatin) are expected to exhibit such phenomena, as they are cross-linked networks that continually experience propagating forces arising from dynamic cellular activity. Additional agitation within these gene-encoding DNA networks could have potential genetic consequences. By changing the local mobility of transcriptional machinery and regulatory proteins towards/from their binding sites, and thereby influencing transcription rates, active fluctuations could prove to be a physical means of modulating gene expression. To begin probing this effect, we construct genetic DNA hydrogels, as a simple, reconstituted model of chromatin, and quantify transcriptional output from these hydrogels in the presence/absence of active fluctuations. [Preview Abstract] |
Wednesday, March 15, 2017 2:03PM - 2:15PM |
L4.00011: A Probabilistic Graphical Model to Detect Chromosomal Domains Dieter Heermann, Andreas Hofmann, Eva Weber To understand the nature of a cell, one needs to understand the structure of its genome. For this purpose, experimental techniques such as Hi-C detecting chromosomal contacts are used to probe the three-dimensional genomic structure. These experiments yield topological information, consistently showing a hierarchical subdivision of the genome into self-interacting domains across many organisms. Current methods for detecting these domains using the Hi-C contact matrix, i.e. a doubly-stochastic matrix, are mostly based on the assumption that the domains are distinct, thus non-overlapping. For overcoming this simplification and for being able to unravel a possible nested domain structure, we developed a probabilistic graphical model that makes no a priori assumptions on the domain structure. Within this approach, the Hi-C contact matrix is analyzed using an Ising like probabilistic graphical model whose coupling constant is proportional to each lattice point (entry in the contact matrix). The results show clear boundaries between identified domains and the background. These domain boundaries are dependent on the coupling constant, so that one matrix yields several clusters of different sizes, which show the self-interaction of the genome on different scales. [Preview Abstract] |
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