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Biophysical Journal

Bekele Gurmessa, Shea Ricketts, Rae M Robertson-Anderson
We use optical tweezers microrheology and fluorescence microscopy to apply nonlinear microscale strains to entangled and cross-linked actin networks, and measure the resulting stress and actin filament deformations. We couple nonlinear stress response and relaxation to the velocities and displacements of individual fluorescent-labeled actin segments, at varying times throughout the strain and varying distances from the strain path, to determine the underlying molecular dynamics that give rise to the debated nonlinear response and stress propagation of cross-linked and entangled actin networks at the microscale...
February 15, 2017: Biophysical Journal
Emmet A Francis, Volkmar Heinrich
The efficient recruitment of immune cells is a vital cornerstone of our defense against infections and a key challenge of immunotherapeutic applications. It relies on the ability of chemotaxing cells to prioritize their responses to different stimuli. For example, immune cells are known to abandon gradients of host-cell-produced cytokines in favor of complement-derived anaphylatoxins, which then guide the cells toward nearby pathogen surfaces. The aptitude to triage stimuli depends on the cells' specific sensitivities to different chemoattractants...
February 6, 2017: Biophysical Journal
Tamar Schlick, Anna Marie Pyle
We describe opportunities and challenges in RNA structural modeling and design, as recently discussed during the second Telluride Science Research Center workshop organized in June 2016. Topics include fundamental processes of RNA, such as structural assemblies (hierarchical folding, multiple conformational states and their clustering), RNA motifs, and chemical reactivity of RNA, as used for structural prediction and functional inference. We also highlight the software and database issues associated with RNA structures, such as the multiple approaches for motif annotation, the need for frequent database updating, and the importance of quality control of RNA structures...
February 2, 2017: Biophysical Journal
Gavin Bascom, Tamar Schlick
While much is known about DNA structure on the basepair level, this scale represents only a fraction of the structural levels involved in folding the genomic material. With recent advances in experimental and theoretical techniques, a variety of structures have been observed on the fiber, gene, and chromosome levels of genome organization. Here we view chromatin architecture from nucleosomes and fibers to genes and chromosomes, highlighting the rich structural diversity and fiber fluidity emerging from both experimental and theoretical techniques...
February 7, 2017: Biophysical Journal
Marco Tompitak, Cédric Vaillant, Helmut Schiessel
Sequences that influence nucleosome positioning in promoter regions, and their relation to gene regulation, have been the topic of much research over the last decade. In yeast, significant nucleosome-depleted regions are found, which facilitate transcription. With the arrival of nucleosome positioning maps for the human genome, it was discovered that in our genome, unlike in that of yeast, promoters encode for high nucleosome occupancy. In this work, we look at the genomes of a range of different organisms, to provide a catalog of nucleosome positioning signals in promoters across the tree of life...
February 7, 2017: Biophysical Journal
Jana Molitor, Jan-Philipp Mallm, Karsten Rippe, Fabian Erdel
Epigenetic modifications and other chromatin features partition the genome on multiple length scales. They define chromatin domains with distinct biological functions that come in sizes ranging from single modified DNA bases to several megabases in the case of heterochromatic histone modifications. Due to chromatin folding, domains that are well separated along the linear nucleosome chain can form long-range interactions in three-dimensional space. It has now become a routine task to map epigenetic marks and chromatin structure by deep sequencing methods...
February 7, 2017: Biophysical Journal
Tamar Schlick, Leslie Loew
No abstract text is available yet for this article.
February 7, 2017: Biophysical Journal
Csaba I Pongor, Pasquale Bianco, György Ferenczy, Richárd Kellermayer, Miklós Kellermayer
Cytosine methylation is a key mechanism of epigenetic regulation. CpG-dense loci, called "CpG islands", play a particularly important role in modulating gene expression. Methylation has long been suspected to alter the physical properties of DNA, but the full spectrum of the evoked changes is unknown. Here we measured the methylation-induced nanomechanical changes in a DNA molecule with the sequence of a CpG island. For the molecule under tension, contour length, bending rigidity and intrinsic stiffness decreased in hypermethylated dsDNA, pointing at structural compaction which may facilitate DNA packaging in vivo...
February 7, 2017: Biophysical Journal
Agnes Noy, Anthony Maxwell, Sarah A Harris
We have explored the interdependence of the binding of a DNA triplex and a repressor protein to distal recognition sites on supercoiled DNA minicircles using MD simulations. We observe that the interaction between the two ligands through their influence on their DNA template is determined by a subtle interplay of DNA mechanics and electrostatics, that the changes in flexibility induced by ligand binding play an important role and that supercoiling can instigate additional ligand-DNA contacts that would not be possible in simple linear DNA sequences...
February 7, 2017: Biophysical Journal
Thomas J Lampo, Stella Stylianidou, Mikael P Backlund, Paul A Wiggins, Andrew J Spakowitz
The cellular cytoplasm is a complex, heterogeneous environment (both spatially and temporally) that exhibits viscoelastic behavior. To further develop our quantitative insight into cellular transport, we analyze data sets of mRNA molecules fluorescently labeled with MS2-GFP tracked in real time in live Escherichia coli and Saccharomyces cerevisiae cells. As shown previously, these RNA-protein particles exhibit subdiffusive behavior that is viscoelastic in its origin. Examining the ensemble of particle displacements reveals a Laplace distribution at all observed timescales rather than the Gaussian distribution predicted by the central limit theorem...
February 7, 2017: Biophysical Journal
Ralf Metzler
No abstract text is available yet for this article.
February 7, 2017: Biophysical Journal
Naoko Tokuda, Masaki Sasai
Recent microscopic and simulation studies have shown that the genome structure fluctuates dynamically in the nuclei of budding yeast Saccharomyces cerevisiae. This genome-wide movement should lead to the fluctuations of individual genes in their territorial regions. This raises an intriguing question of whether the resulting distribution of genes is correlated to their transcriptional activity. An effective method for examining this correlation is to analyze how the spatial distribution of genes and their transcriptional activity are modified by mutation...
February 7, 2017: Biophysical Journal
Georgy N Rychkov, Andrey V Ilatovskiy, Igor B Nazarov, Alexey V Shvetsov, Dmitry V Lebedev, Alexander Y Konev, Vladimir V Isaev-Ivanov, Alexey V Onufriev
The evidence is now overwhelming that partially assembled nucleosome states (PANS) are as important as the canonical nucleosome structure for the understanding of how accessibility to genomic DNA is regulated in cells. We use a combination of molecular dynamics simulation and atomic force microscopy to deliver, in atomic detail, structural models of three key PANS: the hexasome (H2A·H2B)·(H3·H4)2, the tetrasome (H3·H4)2, and the disome (H3·H4). Despite fluctuations of the conformation of the free DNA in these structures, regions of protected DNA in close contact with the histone core remain stable, thus establishing the basis for the understanding of the role of PANS in DNA accessibility regulation...
February 7, 2017: Biophysical Journal
Katelyn Dahlke, Charles E Sing
Recent experimental work has demonstrated facilitated dissociation of certain nucleoid-associated proteins that exhibit an unbinding rate that depends on the concentration of freely diffusing proteins or DNA in solution. This concentration dependence arises due to binding competition with these other proteins or DNA. The identity of the binding competitor leads to different qualitative trends, motivating an investigation to understand observed differences in facilitated dissociation. We use a coarse-grained simulation that takes into account the dimeric nature of many nucleoid-associated proteins by allowing an intermediate binding state...
February 7, 2017: Biophysical Journal
D Thirumalai, Guang Shi
No abstract text is available yet for this article.
February 7, 2017: Biophysical Journal
Stefjord Todolli, Pamela J Perez, Nicolas Clauvelin, Wilma K Olson
One of the critical unanswered questions in genome biophysics is how the primary sequence of DNA bases influences the global properties of very-long-chain molecules. The local sequence-dependent features of DNA found in high-resolution structures introduce irregularities in the disposition of adjacent residues that facilitate the specific binding of proteins and modulate the global folding and interactions of double helices with hundreds of basepairs. These features also determine the positions of nucleosomes on DNA and the lengths of the interspersed DNA linkers...
February 7, 2017: Biophysical Journal
Ruihan Zhang, Jochen Erler, Jörg Langowski
The N-terminal tail of histone H4 is an indispensable mediator for inter-nucleosome interaction, which is required for chromatin fiber condensation. H4K16 acetylation (H4K16Ac) activates gene transcription by influencing both chromatin structure and interplay with nonhistone proteins. To understand the influence of H4K16Ac on inter-nucleosome interaction, we performed a simulation study for the H4 tail in the context of two nucleosomes in neighboring unit cells in the crystal structure. The binding conformation of H4 tail with/without K16Ac was sampled by replica exchange with solute tempering, and the free energy landscape was explored by metadynamics...
February 7, 2017: Biophysical Journal
Bin Zhang, Peter G Wolynes
Energy landscape theory, developed in the context of protein folding, provides, to our knowledge, a new perspective on chromosome architecture. We review what has been learned concerning the topology and structure of both the interphase and mitotic chromosomes from effective energy landscapes constructed using Hi-C data. Energy landscape thinking raises new questions about the nonequilibrium dynamics of the chromosome and gene regulation.
February 7, 2017: Biophysical Journal
Robert Blackwell, Oliver Sweezy-Schindler, Christopher Edelmaier, Zachary R Gergely, Patrick J Flynn, Salvador Montes, Ammon Crapo, Alireza Doostan, J Richard McIntosh, Matthew A Glaser, Meredith D Betterton
Microtubule dynamic instability allows search and capture of kinetochores during spindle formation, an important process for accurate chromosome segregation during cell division. Recent work has found that microtubule rotational diffusion about minus-end attachment points contributes to kinetochore capture in fission yeast, but the relative contributions of dynamic instability and rotational diffusion are not well understood. We have developed a biophysical model of kinetochore capture in small fission-yeast nuclei using hybrid Brownian dynamics/kinetic Monte Carlo simulation techniques...
February 7, 2017: Biophysical Journal
Davide Magatti, Matteo Molteni, Barbara Cardinali, Mattia Rocco, Fabio Ferri
No abstract text is available yet for this article.
January 24, 2017: Biophysical Journal
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