Entropy involved in fidelity of DNA replication

Information has an entropic character which can be analyzed within the Statistical Theory in molecular systems. R. Landauer and C.H. Bennett showed that a logical copy can be carried out in the limit of no dissipation if the computation is performed sufficiently slowly. Structural and recent single-molecule assays have provided dynamic details of polymerase machinery with insight into information processing. We introduce a rigorous characterization of Shannon Information in biomolecular systems and apply it to DNA replication in the limit of no dissipation. Specifically, we devise an equilibrium pathway in DNA replication to determine the entropy generated in copying the information from a DNA template in the absence of friction. Both the initial state, the free nucleotides randomly distributed in certain concentrations, and the final state, a polymerized strand, are mesoscopic equilibrium states for the nucleotide distribution. We use empirical stacking free energies to calculate the probabilities of incorporation of the nucleotides. The copied strand is, to first order of approximation, a state of independent and non-indentically distributed random variables for which the nucleotide that is incorporated by the polymerase at each step is dictated by the template strand, and to second order of approximation, a state of non-uniformly distributed random variables with nearest-neighbor interactions for which the recognition of secondary structure by the polymerase in the resultant double-stranded polymer determines the entropy of the replicated strand. Two incorporation mechanisms arise naturally and their biological meanings are explained. It is known that replication occurs far from equilibrium and therefore the Shannon entropy here derived represents an upper bound for replication to take place. Likewise, this entropy sets a universal lower bound for the copying fidelity in replication.Comment: 25 pages, 5 figure

Information management in DNA replication modeled by directional, stochastic chains with memory

[EN] Stochastic chains represent a key variety of phenomena in many branches of science within the context of information theory and thermodynamics. They are typically approached by a sequence of independent events or by a memoryless Markov process. Stochastic chains are of special significance to molecular biology, where genes are conveyed by linear polymers made up of molecular subunits and transferred from DNA to proteins by specialized molecular motors in the presence of errors. Here, we demonstrate that when memory is introduced, the statistics of the chain depends on the mechanism by which objects or symbols are assembled, even in the slow dynamics limit wherein friction can be neglected. To analyze these systems, we introduce a sequence-dependent partition function, investigate its properties, and compare it to the standard normalization defined by the statistical physics of ensembles. We then apply this theory to characterize the enzyme-mediated information transfer involved in DNA replication under the real, non-equilibrium conditions, reproducing measured error rates and explaining the typical 100-fold increase in fidelity that is experimentally found when proofreading and edition take place. Our model further predicts that approximately 1 kT has to be consumed to elevate fidelity in one order of magnitude. We anticipate that our results are necessary to interpret configurational order and information management in many molecular systems within biophysics, materials science, communication, and engineering. Published by AIP Publishing.It is a pleasure to thank J. M. R. Parrondo and D. G. Aleja for fruitful discussion. This work was supported the Spanish Ministry of Economy and Competitiveness (Grant Nos. MAT2013-49455-EXP and MAT2015-71806-R).Arias-Gonzalez, JR. (2016). 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Multiplexed vortex beam-based optical tweezers

The design and implementation of a multiplexed spiral phase mask in an experimental optical tweezer setup are presented. This diffractive optical element allows the generation of multiple concentric vortex beams with independent topological charges. The generalization of the phase mask for multiple concentric vortices is also shown. The design for a phase mask of two multiplexed vortices with different topological charges is developed. We experimentally show the transfer of angular momentum to the optically trapped microparticles by enabling orbiting dynamics around the optical axis independently within each vortex. The angular velocity of the confined particles versus the optical power in the focal region is also discussed for different combinations of topological charges

Photoluminescence Activation of Organic Dyes via Optically Trapped Quantum Dots

This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Nano, copyright © American Chemical Society after peer review and technical editing by the publisher.[EN] Laser tweezers afford quantum dot (QD) manipulation for use as localized emitters. Here, we demonstrate fluorescence by radiative energy transfer from optically trapped colloidal QDs (donors) to fluorescent dyes (acceptors). To this end, we synthesized silica-coated QDs of different compositions and triggered their luminescence by simultaneous trapping and two-photon excitation in a microfluidic chamber filled with dyes. This strategy produces a near-field light source with great spatial maneuverability, which can be exploited to scan nanostructures. In this regard, we demonstrate induced photoluminescence of dye-labeled cells via optically trapped silica-coated colloidal QDs placed at their vicinity. Allocating nanoscale donors at controlled distances from a cell is an attractive concept in fluorescence microscopy because it dramatically reduces the number of excited dyes, which improves resolution by preventing interferences from the whole sample, while prolonging dye luminescence lifetime due to the lower power absorbed from the QDs.H.R.-R. is supported by an FPI-UAM 2015 fellowship (BES-2009-027909). Authors acknowledge funding from the Spanish Ministry of Economy and Competitiveness through MAT2017-85617-R and MAT2015-71806-R. B.H.J. acknowledges financial support from the Spanish Ministry of Economy and Competitiveness, through the Maria de Maeztu (IFIMAC) and Severo Ochoa (IMDEA Nanoscience) Programmes for Units of Excellence in R&D.Rodríguez-Rodríguez, H.; Acebrón, M.; Iborra, F.; Arias-Gonzalez, JR.; Juárez, B. (2019). Photoluminescence Activation of Organic Dyes via Optically Trapped Quantum Dots. ACS Nano. 13(6):7223-7230. https://doi.org/10.1021/acsnano.9b02835S7223723013

A Temperature-Jump Optical Trap for Single-Molecule Manipulation

[EN] To our knowledge, we have developed a novel temperature-jump optical tweezers setup that changes the temperature locally and rapidly. It uses a heating laser with a wavelength that is highly absorbed by water so it can cover a broad range of temperatures. This instrument can record several force-distance curves for one individual molecule at various temper- atures with good thermal and mechanical stability. Our design has features to reduce convection and baseline shifts, which have troubled previous heating-laser instruments. As proof of accuracy, we used the instrument to carry out DNA unzipping experi- ments in which we derived the average basepair free energy, entropy, and enthalpy of formation of the DNA duplex in a range of temperatures between 5 C and 50 C. We also used the instrument to characterize the temperature-dependent elasticity of single-stranded DNA (ssDNA), where we find a significant condensation plateau at low force and low temperature. Oddly, the persistence length of ssDNA measured at high force seems to increase with temperature, contrary to simple entropic models.The authors thank J. Camunas and S. Frutos for contributing the molecules used in the experiments, and J.M. Huguet for helpful discussion. F.R. is supported by grant Institucio Catalana de Recerca i Estudis Avancats Academia 2013 and J.R. A.-G. by an Explora grant from MINECO (MAT2013-49455-EXP). The research that led to the results presented here was funded by the European Union Seventh Framework Programme (FP7/2007-2013) under grant 308850 INFERNOS and European Research Council grant MagReps (No. 267862).De Lorenzo, S.; Ribezzi-Crivellari, M.; Arias-Gonzalez, JR.; Smith, S.; Ritort, F. (2015). A Temperature-Jump Optical Trap for Single-Molecule Manipulation. Biophysical Journal. 108(12):2854-2864. https://doi.org/10.1016/j.bpj.2015.05.017S285428641081

Asymptotically Lifshitz wormholes and black holes for Lovelock gravity in vacuum

Static asymptotically Lifshitz wormholes and black holes in vacuum are shown to exist for a class of Lovelock theories in d=2n+1>7 dimensions, selected by requiring that all but one of their n maximally symmetric vacua are AdS of radius l and degenerate. The wormhole geometry is regular everywhere and connects two Lifshitz spacetimes with a nontrivial geometry at the boundary. The dynamical exponent z is determined by the quotient of the curvature radii of the maximally symmetric vacua according to n(z^2-1)+1=(l/L)^2, where L corresponds to the curvature radius of the nondegenerate vacuum. Light signals are able to connect both asymptotic regions in finite time, and the gravitational field pulls towards a fixed surface located at some arbitrary proper distance to the neck. The asymptotically Lifshitz black hole possesses the same dynamical exponent and a fixed Hawking temperature given by T=z/(2^z pi l). Further analytic solutions, including pure Lifshitz spacetimes with a nontrivial geometry at the spacelike boundary, and wormholes that interpolate between asymptotically Lifshitz spacetimes with different dynamical exponents are also found.Comment: 19 pages, 1 figur

Mechanical unfolding of long human telomeric RNA (TERRA)

[EN] We report the first single molecule investigation of TERRA molecules. By using optical-tweezers and other biophysical techniques, we have found that long RNA constructions of up to 25 GGGUUA repeats form higher order structures comprised of single parallel G-quadruplex blocks, which unfold at lower forces than their DNA counterparts.This work was supported by grants from the Spanish Ministry of Science and Innovation (grants RYC2007-01765 to JRA-G, BFU2011-30295-C02-01 to AV, and CTQ2010-21567-C02-02 to CG). MG was supported by the FPI fellowship BES-2009-027909. RB and EH-G were supported by Comunidad de Madrid, grant CAM-S2009MAT-1507. AV acknowledges an institutional grant from the Fundacion Ramon Areces to the CBMSO. JRA-G wants to thank Prof. J. L. Carrascosa and Prof. J. M. Valpuesta (CNB-CSIC) for their continuous support and encouragement in this research. 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