Chromatin: a tunable spring at work inside chromosomes

This paper focuses on mechanical aspects of chromatin biological functioning. Within a basic geometric modeling of the chromatin assembly, we give for the first time the complete set of elastic constants (twist and bend persistence lengths, stretch modulus and twist-stretch coupling constant) of the so-called 30-nm chromatin fiber, in terms of DNA elastic properties and geometric properties of the fiber assembly. The computation naturally embeds the fiber within a current analytical model known as the ``extensible worm-like rope'', allowing a straightforward prediction of the force-extension curves. We show that these elastic constants are strongly sensitive to the linker length, up to 1 bp, or equivalently to its twist, and might locally reach very low values, yielding a highly flexible and extensible domain in the fiber. In particular, the twist-stretch coupling constant, reflecting the chirality of the chromatin fiber, exhibits steep variations and sign changes when the linker length is varied. We argue that this tunable elasticity might be a key feature for chromatin function, for instance in the initiation and regulation of transcription.Comment: 38 pages 15 figure

Statistical-mechanical lattice models for protein-DNA binding in chromatin

Statistical-mechanical lattice models for protein-DNA binding are well established as a method to describe complex ligand binding equilibriums measured in vitro with purified DNA and protein components. Recently, a new field of applications has opened up for this approach since it has become possible to experimentally quantify genome-wide protein occupancies in relation to the DNA sequence. In particular, the organization of the eukaryotic genome by histone proteins into a nucleoprotein complex termed chromatin has been recognized as a key parameter that controls the access of transcription factors to the DNA sequence. New approaches have to be developed to derive statistical mechanical lattice descriptions of chromatin-associated protein-DNA interactions. Here, we present the theoretical framework for lattice models of histone-DNA interactions in chromatin and investigate the (competitive) DNA binding of other chromosomal proteins and transcription factors. The results have a number of applications for quantitative models for the regulation of gene expression.Comment: 19 pages, 7 figures, accepted author manuscript, to appear in J. Phys.: Cond. Mat

Spin-boson models for quantum decoherence of electronic excitations of biomolecules and quantum dots in a solvent

We give a theoretical treatment of the interaction of electronic excitations (excitons) in biomolecules and quantum dots with the surrounding polar solvent. Significant quantum decoherence occurs due to the interaction of the electric dipole moment of the solute with the fluctuating electric dipole moments of the individual molecules in the solvent. We introduce spin boson models which could be used to describe the effects of decoherence on the quantum dynamics of biomolecules which undergo light-induced conformational change and on biomolecules or quantum dots which are coupled by Forster resonant energy transfer.Comment: More extended version, to appear in Journal of Physics: Condensed Matter. 13 pages, 3 figure

Die quantitative Bestimmung des Paraffins in den hochsiedenden Destillaten des Rohpetroleums

n/

NucTools: analysis of chromatin feature occupancy profiles from high-throughput sequencing data

Background: Biomedical applications of high-throughput sequencing methods generate a vast amount of data in which numerous chromatin features are mapped along the genome. The results are frequently analysed by creating binary data sets that link the presence/absence of a given feature to specific genomic loci. However, the nucleosome occupancy or chromatin accessibility landscape is essentially continuous. It is currently a challenge in the field to cope with continuous distributions of deep sequencing chromatin readouts and to integrate the different types of discrete chromatin features to reveal linkages between them. Results: Here we introduce the NucTools suite of Perl scripts as well as MATLAB- and R-based visualization programs for a nucleosome-centred downstream analysis of deep sequencing data. NucTools accounts for the continuous distribution of nucleosome occupancy. It allows calculations of nucleosome occupancy profiles averaged over several replicates, comparisons of nucleosome occupancy landscapes between different experimental conditions, and the estimation of the changes of integral chromatin properties such as the nucleosome repeat length. Furthermore, NucTools facilitates the annotation of nucleosome occupancy with other chromatin features like binding of transcription factors or architectural proteins, and epigenetic marks like histone modifications or DNA methylation. The applications of NucTools are demonstrated for the comparison of several datasets for nucleosome occupancy in mouse embryonic stem cells (ESCs) and mouse embryonic fibroblasts (MEFs). Conclusions: The typical workflows of data processing and integrative analysis with NucTools reveal information on the interplay of nucleosome positioning with other features such as for example binding of a transcription factor CTCF, regions with stable and unstable nucleosomes, and domains of large organized chromatin K9me2 modifications (LOCKs). As potential limitations and problems we discuss how inter-replicate variability of MNase-seq experiments can be addressed

Two approaches to the study of the origin of life.

This paper compares two approaches that attempt to explain the origin of life, or biogenesis. The more established approach is one based on chemical principles, whereas a new, yet not widely known approach begins from a physical perspective. According to the first approach, life would have begun with - often organic - compounds. After having developed to a certain level of complexity and mutual dependence within a non-compartmentalised organic soup, they would have assembled into a functioning cell. In contrast, the second, physical type of approach has life developing within tiny compartments from the beginning. It emphasises the importance of redox reactions between inorganic elements and compounds found on two sides of a compartmental boundary. Without this boundary, ¿life¿ would not have begun, nor have been maintained; this boundary - and the complex cell membrane that evolved from it - forms the essence of life

Force-dependent binding constants

Life is an emergent property of transient interactions between biomolecules and other organic and inorganic molecules that somehow leads to harmony and order. Measurement and quantitation of these biological interactions is of value to scientists, and is a major goal of biochemistry, as affinities provide insight into biological processes. In an organism these interactions occur in the context of forces and the need for a consideration of binding affinities in the context of a changing mechanical landscape necessitates a new way to consider the biochemistry of protein-protein interactions. In the last few decades the field of Mechanobiology has exploded, as both the appreciation, and the technical advances required to facilitate the study, of how forces impact on biological processes has become evident. The aim of this review is to introduce the concept of force-dependence of biomolecular interactions, and the requirement to be able to measure force-dependent binding constants. The focus of this discussion will be on the mechanotransduction that occurs at the integrin-mediated adhesions with the extracellular matrix, and the major mechanosensors talin and vinculin. However, the approaches that the cell uses to sense and respond to forces are applicable to other systems, and therefore provides a general discussion of the force-dependence of biomolecule interactions

Saturation Behavior: a general relationship described by a simple second-order differential equation

<p>Abstract</p> <p>Background</p> <p>The numerous natural phenomena that exhibit saturation behavior, <it>e.g</it>., ligand binding and enzyme kinetics, have been approached, to date, via empirical and particular analyses. This paper presents a mechanism-free, and assumption-free, second-order differential equation, designed only to describe a typical relationship between the variables governing these phenomena. It develops a mathematical model for this relation, based solely on the analysis of the typical experimental data plot and its saturation characteristics. Its utility complements the traditional empirical approaches.</p> <p>Results</p> <p>For the general saturation curve, described in terms of its independent (<it>x</it>) and dependent (<it>y</it>) variables, a second-order differential equation is obtained that applies to any saturation phenomena. It shows that the driving factor for the basic saturation behavior is the probability of the interactive site being free, which is described quantitatively. Solving the equation relates the variables in terms of the two empirical constants common to all these phenomena, the initial slope of the data plot and the limiting value at saturation. A first-order differential equation for the slope emerged that led to the concept of the effective binding rate at the active site and its dependence on the calculable probability the interactive site is free. These results are illustrated using specific cases, including ligand binding and enzyme kinetics. This leads to a revised understanding of how to interpret the empirical constants, in terms of the variables pertinent to the phenomenon under study.</p> <p>Conclusions</p> <p>The second-order differential equation revealed the basic underlying relations that describe these saturation phenomena, and the basic mathematical properties of the standard experimental data plot. It was shown how to integrate this differential equation, and define the common basic properties of these phenomena. The results regarding the importance of the slope and the new perspectives on the empirical constants governing the behavior of these phenomena led to an alternative perspective on saturation behavior kinetics. Their essential commonality was revealed by this analysis, based on the second-order differential equation.</p