Bulletin of the American Physical Society
APS March Meeting 2019
Volume 64, Number 2
Monday–Friday, March 4–8, 2019; Boston, Massachusetts
Session B64: Biopolymers I (DNA, RNA, Biocompatible, Gels)Focus
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Sponsoring Units: DBIO Room: BCEC 259B |
Monday, March 4, 2019 11:15AM - 11:27AM |
B64.00001: Inferring the helix-helix electrostatic interaction strength from the structure of dense DNA toroids Luca Barberi, Amélie Leforestier, Françoise Livolant, Martin Lenz DNA is often condensed to remarkably dense phases, where one or more chains are curved at scales comparable to their persistence length. This can happen in the presence of highly valent cations, like in the capsids of some bacteriophage viruses, where a long DNA chain is rolled up to nearly crystalline densities with spermidine(3+) and putrescine(2+). Despite their biological relevance, cation-mediated helix-helix electrostatic interactions remain poorly understood and their experimental measurement limited to arrays of locally parallel DNA helices. These forces relying on strong spatial correlations between charges on neighbouring helices, straight DNA chains may interact differently than curved ones. We are able to infer the strength of helix-helix electrostatic forces in a spermine(4+)-condensed DNA toroid, predicting with a minimal model the inter-helical spacing spatial inhomogeneities observed in our recent cryo-electron microscopy experiments. Our results suggest that electrostatic cohesion may be one order of magnitude weaker in toroids than in other DNA condensates with less local curvature. Curvature-reduced electrostatic interactions may facilitate DNA ejection dynamics in bacteriophages. |
Monday, March 4, 2019 11:27AM - 11:39AM |
B64.00002: The Nanomechanics of Cellulose Synthesis Lori Goldner, Nina Zehfroosh, Tobias I. Baskin Despite its ubiquity and technological importance, cellulose is synthesized in plants by a process that is poorly understood. Cellulose is a crystalline fiber made up of glucan chains synthesized by a large enzymatic complex that resides in the plant cell membrane. Decisive progress was made more than a decade ago when fluorescently-tagged complexes were first observed moving in the cell membranes of living plants. Complexes move with a speed between 100 and 400 nm/min and this motion is presumed to be related to the rate of cellulose synthesis. We present the results of a careful study of CESA motion in two different plant species over a wide range of timescales. We show several surprising aspects of this motion and discuss models to explain it. After accounting for localization error, the mean squared displacement (MSD) of the moving cellulose synthase complexes shows subdiffusive timescales below 10 seconds suggesting short-range trapping. Over longer timescales, an extant model and particle MSDs support a Brownian ratchet mechanism. However, initial indications are that step-size distributions are non-Gaussian, indicating that a Brownian ratchet alone may not be sufficient to explain CESA mechanics. |
Monday, March 4, 2019 11:39AM - 11:51AM |
B64.00003: On the behavior of random RNA secondary structures near the glass transition William Baez, Kay J\"{o}rg Wiese, Ralf Bundschuh RNA forms elaborate secondary structures through intramolecular base pairing. These structures perform critical biological functions within each cell. Due to the availability of a polynomial algorithm to calculate the partition function over these structures, they are also a suitable system for the statistical physics of disordered systems. In this model, below the denaturation temperature, random RNA secondary structures exist in one of two phases: a strongly disordered, low-temperature glass phase, and a weakly disordered, high-temperature molten phase. The probability of two bases to pair decays with their distance with an exponent 3/2 in the molten phase, and about 4/3 in the glass phase. Inspired by previous results from a renormalized field theory of the glass transition separating the two phases, we numerically study this transition. We introduce distinct order parameters for each phase, that both vanish at the critical point. We finally explore the driving mechanism behind this transition. |
Monday, March 4, 2019 11:51AM - 12:03PM |
B64.00004: Salivary mucin glycopolymers reduce virulence traits of cavity-causing Streptococcus mutans Caroline Werlang, Wesley Chen, Katharina Ribbeck Dry mouth is a condition characterized by an underproduction of saliva that affects one in five American adults. This reduction in salivary mucus is associated with higher incidences of cavities, oral ulcers, and microbial infections in the mouth. Saliva’s protective effects are derived from mucins, gel-forming proteins. These natural brush polymers display over two-hundred unique glycan motifs. Reconstituted salivary mucin gels have been shown to prevent biofilm formation of Streptococcus mutans, bacteria whose adherence to teeth causes cavities. Here, we show that mucin affects other virulence behaviors of these bacteria, reducing population-level signaling and gene transfer, which can spread antibiotic resistance. This evidence points to mucin gels’ unique ability to regulate the phenotypes of potentially pathogenic microbes. We also present our continuing efforts to design synthetic mucin-mimetic glycopolymers and test their efficacy at reducing microbial virulence. We hope that these principles can be used to develop mucin-inspired therapeutic polymers that could potentially alleviate the severity of dry mouth related symptoms based off of saliva’s natural protection mechanisms. |
Monday, March 4, 2019 12:03PM - 12:15PM |
B64.00005: Molecular characterization of mucus binding Jacob Witten, Tahoura Samad, Katharina Ribbeck Mucus coats all wet epithelial surfaces of the body. Binding of small molecules to mucus has an important role in human health, as it may affect the diffusivity and activity of drugs and toxins that act in a mucosal environment. Despite the importance of mucus-small molecule binding, there is a lack of data revealing the precise physicochemical features of small molecules that lead to mucus binding. We developed a novel equilibrium dialysis assay to measure the binding of small molecules to mucin and other mucus components at unprecedented throughput, and combined this assay with a small molecule microarray to identify a novel mucin binding motif. Furthermore, we showed that for molecules with this motif, binding to mucins and the mucus-associated biopolymers DNA and alginate is modulated by differences in hydrophobicity and charge. Finally, we showed that molecules without the motif exhibited different trends from molecules with the motif, suggesting a complex dependence of mucin binding on molecular physicochemical properties. |
Monday, March 4, 2019 12:15PM - 12:27PM |
B64.00006: Microfluidic delivery of cutting enzymes for fragmentation of surface-adsorbed DNA molecules. Julia Budassi, Alan Gan, Albert Tian, Jonathan Sokolov We describe a method for fragmenting DNA molecules surface-adsorbed and immobilized onto a polymethyl |
Monday, March 4, 2019 12:27PM - 12:39PM |
B64.00007: Anomalous, non-Gaussian, viscoelastic and age-dependent dynamics of histone-like nucleoid structuring proteins in live Escherichia coli Yong Wang, Asmaa Sadoon We report our measurements of the dynamics of H-NS proteins, which interact with both proteins and DNA simultaneously, in live E. coli bacteria. The dynamics turn out to differ significantly from other molecules reported previously. A new power-law distribution was observed for the diffusion coefficients of individual H-NS proteins. In addition, we observed a new distribution of displacements, which does not follow the Gaussian, Cauchy, or Laplace distributions, but the Pearson Type VII distribution. Furthermore, we experimentally measured, for the first time, the time/frequency dependence of the complex modulus of the bacterial cytoplasm, which deviates from the viscoelasticity of homogeneous protein solutions and shows a glass-liquid transition. Lastly, we observed that the dynamics of H-NS protein is cell-length/cell-age dependent. The findings are expected to fundamentally change the current views on bacterial cytoplasm and diffusional dynamics of molecules in bacteria. |
Monday, March 4, 2019 12:39PM - 12:51PM |
B64.00008: Spatially-defined active matter using DNA strands Anis Senoussi, Jean-Christophe Galas, André Estevez-Torres Living systems have the incredible ability to organize themselves from molecules to the macroscopic scale. To understand the complex processes involved, we are reproducing some features of morphogenesis by rationally designing spatiotemporal patterns in artificial active materials. Taking advantages of the predictable interactions between their sequences, we use nucleic acids as elementary bricks to build complex active systems. |
Monday, March 4, 2019 12:51PM - 1:03PM |
B64.00009: Selective response of DNA sequences at THz frequencies from numerical simulation Alexander Shvonski, Victoria Gabriele, Krzysztof Kempa We numerically simulate the response of DNA sequences to driving with THz radiation using the dynamical model of Ref. [1]. Homogeneous sequences of AT base-pairs experience an amplitude response that is distinct from homogeneous GC sequences in the parameter space of driving amplitude and frequency. Heterogeneous sequences with the same number of AT and GC pairs, but different ordering, also exhibit distinct responses in some regions of parameter space. Results indicate that THz driving is selective between different DNA sequences. [1] R. Tapia-Rojo, J. J. Mazo, and F. Falo, “Thermal and mechanical properties of a DNA model with solvation barrier,” Physical Review E 82, 031916 (2010). |
Monday, March 4, 2019 1:03PM - 1:15PM |
B64.00010: Surprising Charge Transport in DNA Roman Zhuravel The field of Nano-electronics concentrates a lot of interest from technological and scientific points of view. While charge transport in the solid state has been widely researched, for large single molecules many fundamental questions remain unsolved. |
Monday, March 4, 2019 1:15PM - 1:27PM |
B64.00011: RNA structure and kinetics including pseudoknots through complete landscape enumeration Ofer Kimchi, Tristan Cragnolini, Rees F Garmann, Vinothan N Manoharan, Michael Phillip Brenner, Lucy Colwell Kinetic barriers as well as non-nested loops (pseudoknots) still pose challenges in the accurate prediction of RNA secondary structure. We will (1) develop a physical model to estimate the entropies of complex pseudoknots; and (2) demonstrate that their NP-complete enumeration need not impede their study. Our novel polymer physics model can address arbitrarily complex pseudoknots using only two free parameters corresponding to concrete physical quantities -- over an order of magnitude fewer than the sparsest state-of-the-art phenomenological methods. By coupling this model to exhaustive enumeration of the set of possible structures, we compute the entire free energy landscape of secondary structures resulting from a primary RNA sequence. Despite our model's parametric sparsity, it performs on par or better than previously published methods in predicting both pseudoknotted and non-pseudoknotted structures on a benchmark dataset of RNA structures of ≤ 80 nucleotides. We discuss the implications of the complete enumeration procedure employed for the study of kinetics. |
Monday, March 4, 2019 1:27PM - 1:39PM |
B64.00012: Protamine progressively folds DNA before looping Obinna Ukogu, Adam Smith, Luka Devenica, Hilary Bediako, Ashley Carter In sperm, protamine proteins cause a rapid condensation of the DNA to almost crystalline packing levels. Understanding the physical mechanism for this dramatic process is an important limiting case in biophysics. In addition, protamine condensation of DNA may be useful in biomaterials research to assemble or fold DNA nanostructures. Here our goal is to understand the first step in the pathway, the folding of the DNA into a single loop by protamine. To answer this question, we image single molecules of DNA with bound protamine using an atomic force microscope (AFM). We also directly measure DNA folding dynamics in real time using tethered particle motion (TPM) assays. We expected our measurements to show a single folding event as the loop forms, but both measurements showed the presence of multiple, long-lived (100 s) intermediates. Structurally, these intermediates are half-loops or “c-shapes” that become more folded over as the protamine concentration increases. This data suggests a new model for DNA looping whereby small molecules coat the DNA and progressively fold it before forming a loop. |
Monday, March 4, 2019 1:39PM - 1:51PM |
B64.00013: DNA Base-Pairing Visualized by Liquid-Cell Transmission Electron Microscopy Huan Wang, Bo Li, Ye-Jin Kim, Oh-Hoon Kwon, Steve Granick We show that fragile biological samples including DNA can be imaged using in situ transmission electron microscopy (TEM) without metal staining. Reporting statistical analysis of large datasets concerning single-strand and double-stranded aqueous DNA trapped in creases between paired graphene sheets, we visualize individual molecules with ~1 nm spatial resolution and ~100 ms time resolution for up to ~3 min, apparently without significant perturbation from the electron beam. Inspecting the time-dependent base-pairing of single-stranded DNA base-pairing, some pathways are as anticipated while others are surprising. |
Monday, March 4, 2019 1:51PM - 2:03PM |
B64.00014: Zippering dynamics of an RNA hairpin: Role of helicity Huaping Li, Alkan Kabakcioglu Despite several computational studies on hairpin folding and some supporting experimental data, role of the helical geometry on hairpin folding dynamics remains mostly unexplored. We here address this question by means of extensive molecular dynamics simulations on helical and (non-helical) "ladder-like" coarse-grained models. It is known that the folding time (τ) of a thermally quenched RNA hairpin depends on the number of base pairs (N) as τ ~ Nα , where α=1+ν is found to fit the experimental data with ν≈ 0.6 (Flory exponent in three dimensions). We find that α changes from 1.6 to 1.2 ( ≈ 2ν) in three dimensions when duplex helicity is removed. Simulations in two dimensions (ν = 0.75) and with a ghost chain (ν = 0.5) further support the hypothesis α=2ν for a "ladder-like" hairpin. The contrast between the two models which have identical single-strand properties suggests that duplex dynamics is a relevant component of the folding process, hence contradicting the theoretical models focusing on the non-equilibrium behavior of the unpaired segments alone. We propose a new scaling argument for α=1+ν in helical chains and an energy argument for α ≧ 2ν. |
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