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  • How cytoplasmic dynein couples ATP hydrolysis cycle to diverse stepping motions: kinetic modeling
    Biophys. J. (IF 3.665) Pub Date : 2020-03-29
    Shintaroh Kubo; Tomohiro Shima; Shoji Takada

    Cytoplasmic dynein is a two-headed molecular motor that moves to the minus end of a microtubule (MT) by ATP hydrolysis free energy. By employing its two heads (motor domains), cytoplasmic dynein exhibits various bipedal stepping motions; inchworm and hand-over-hand motions, as well as non-alternating steps of one head. However, the molecular basis to achieve such diverse stepping manners remains unclear

    更新日期:2020-03-31
  • Excess dNTPs trigger oscillatory surface flow in the early Drosophila embryo
    Biophys. J. (IF 3.665) Pub Date : 2020-03-29
    Sayantan Dutta; Nareg J.-V. Djabrayan; elia M. Smits; Clarence W. Rowley; Stanislav Y. Shvartsman

    During the first two hours of Drosophila development, precisely orchestrated nuclear cleavages, cytoskeletal rearrangements, and directed membrane growth lead to the formation of an epithelial sheet around the yolk. The newly formed epithelium remains relatively quiescent during the next hour, as it is patterned by maternal inductive signals and zygotic gene products. We discovered that this mechanically

    更新日期:2020-03-31
  • Lipid Organization in Mixed Lipid Membranes Driven by Intrinsic Curvature Difference
    Biophys. J. (IF 3.665) Pub Date : 2020-03-29
    Radha Ranganathan; Intisar Alshammri; Miroslav Peric

    Laurdan fluorescence, novel spectral fitting and Dynamic Light Scattering (DLS) were combined to determine lateral lipid organization in mixed lipid membranes of the oxidized lipid, 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine (PGPC) and each of the three bilayer lipids: 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1-Palmitoyl-2-oleoylphosphatidylcholine

    更新日期:2020-03-31
  • Membrane protein dimerization in cell-derived lipid membranes measured by FRET with MC simulations
    Biophys. J. (IF 3.665) Pub Date : 2020-03-29
    J. Škerle; J. Humpolíčková; N. Johnson; P. Rampírová; E. Poláchová; M. Fliegl; J. Dohnálek; A. Suchánková; D. Jakubec; K. Strisovsky

    Many membrane proteins are thought to function as dimers or higher oligomers, but measuring membrane protein oligomerization in lipid membranes is particularly challenging. Förster resonance energy transfer (FRET) and fluorescence cross-correlation spectroscopy (FCCS) are non-invasive, optical methods of choice that have been applied to the analysis of dimerization of single-spanning membrane proteins

    更新日期:2020-03-31
  • Lipid-Protein Interactions are a Unique Property and Defining Feature of G Protein-Coupled Receptors
    Biophys. J. (IF 3.665) Pub Date : 2020-03-20
    Besian I. Sejdiu; D. Peter Tieleman

    G Protein-Coupled Receptors (GPCRs) are membrane-bound proteins that depend on their lipid environment to carry out their physiological function. Combined efforts from many theoretical and experimental studies on the lipid-protein interaction profile of several GPCRs hint at an intricate relationship of these receptors with their surrounding membrane environment, with several lipids emerging as particularly

    更新日期:2020-03-21
  • Extraction of thick filaments in individual sarcomeres affects force production by single myofibrils
    Biophys. J. (IF 3.665) Pub Date : 2020-03-19
    Andrea C. Mendoza; Dilson E. Rassier

    It has been accepted that the force produced by a skeletal muscle myofibril depends on its cross-sectional area, but not on the number of active sarcomeres since they are arranged in series. However, a previous study performed by our group showed that blocking actomyosin interactions within an activated myofibril and depleting the thick filaments in one sarcomere unexpectedly reduced force production

    更新日期:2020-03-19
  • A disorder-to-order transition mediates RNA-binding of the Caenorhabditis elegans protein MEX-5
    Biophys. J. (IF 3.665) Pub Date : 2020-03-19
    Davide Tavella; Asli Ertekin; Hila Schaal; Sean P. Ryder; Francesca Massi

    CCCH-type tandem zinc finger (TZF) domains are found in many RNA-binding proteins (RBPs) that regulate the essential processes of post-transcriptional gene expression and splicing through direct protein-RNA interactions. In Caenorhabditis elegans, RBPs control the translation, stability, or localization of maternal mRNAs required for patterning decisions prior to zygotic gene activation. MEX-5 is a

    更新日期:2020-03-19
  • Presence or absence of Ras-dimerization shows distinct kinetic signature in Ras-Raf interaction
    Biophys. J. (IF 3.665) Pub Date : 2020-03-14
    Sumantra Sarkar; Angel E. García

    Initiations of cell-signaling pathways often occur through the formation of multiprotein complexes that form through protein-protein interactions. Therefore, detecting their presence is central to understanding the function of a cell-signaling pathway, aberration of which often leads to fatal diseases, including cancers. However, the multiprotein complexes are often difficult to detect using microscopes

    更新日期:2020-03-16
  • Protein structure prediction and design in a biologically realistic implicit membrane
    Biophys. J. (IF 3.665) Pub Date : 2020-03-14
    Rebecca F. Alford; Patrick J. Fleming; Karen G. Fleming; Jeffrey J. Gray

    Protein design is a powerful tool for elucidating mechanisms of function and engineering new therapeutics and nanotechnologies. While soluble protein design has advanced, membrane protein design remains challenging due to difficulties in modeling the lipid bilayer. In this work, we developed an implicit approach that captures the anisotropic structure, shape of water-filled pores, and nanoscale dimensions

    更新日期:2020-03-16
  • Measuring stepwise binding of thermally fluctuating particles to cell membranes without fluorescence
    Biophys. J. (IF 3.665) Pub Date : 2020-03-14
    Aleander Rohrbach; Tim Meyer; Ernst H.K. Stelzer; Holger Kress

    Thermal motions enable a particle to probe the optimal interaction state when binding to a cell membrane. However, especially on the scale of microseconds and nanometers, position and orientation fluctuations are difficult to observe with common measurement technologies. Here we show that it is possible to detect single binding events of IgG-coated polystyrene beads, which are held in an optical trap

    更新日期:2020-03-16
  • Mechanical regulation of neurite polarization and growth – A computational study
    Biophys. J. (IF 3.665) Pub Date : 2020-03-14
    Maximilian A.H. Jakobs; Kristian Franze; Assaf Zemel

    The densely packed microtubule (MT) array found in neuronal cell projections (neurites) serves two fundamental functions simultaneously: It provides a mechanically stable track for molecular-motor based transport, and produces forces which drive neurite growth. The local pattern of MT polarity along the neurite shaft has been found to differ between axons and dendrites. In axons, the neurons’ dominating

    更新日期:2020-03-16
  • The kinesin-8 Kip3 depolymerizes microtubules with a collective force-dependent mechanism
    Biophys. J. (IF 3.665) Pub Date : 2020-03-14
    Michael Bugiel; Mayank Chugh; Tobias Jörg Jachowski; Erik Schäffer; Anita Jannasch

    Microtubules are highly dynamic filaments with dramatic structural rearrangements and length changes during the cell cycle. An accurate control of the microtubule length is essential for many cellular processes, in particular during cell division. Motor proteins from the kinesin-8 family depolymerize microtubules by interacting with their ends in a collective and length-dependent manner. However, it

    更新日期:2020-03-16
  • Atomic force microscopy visualizes mobility of photosynthetic proteins in grana thylakoid membranes
    Biophys. J. (IF 3.665) Pub Date : 2020-03-13
    Bibiana Onoa; Shingo Fukuda; Masakazu Iwai; Carlos Bustamante; Krishna K. Niyogi

    Thylakoid membranes in chloroplasts contain photosynthetic protein complexes that convert light energy into chemical energy. Photosynthetic protein complexes are considered to undergo structural reorganization to maintain the efficiency of photochemical reactions. A detailed description of the mobility of photosynthetic complexes in real-time is necessary to understand how macromolecular organization

    更新日期:2020-03-16
  • Friction-limited Folding of Disulfide-Reduced Monomeric SOD1
    Biophys. J. (IF 3.665) Pub Date : 2020-03-12
    N.R. Cohen; C. Kayatekin; J.A. Zitzewitz; O. Bilsel; C.R. Matthews

    The folding reaction of a stable monomeric variant of Cu/Zn superoxide dismutase (mSOD1), an enzyme responsible for the conversion of superoxide free radicals into hydrogen peroxide and oxygen, is among the slowest known folding processes that adhere to two-state behavior. The long lifetime, ∼10 s, of the unfolded state presents ample opportunities for the polypeptide chain to transiently sample nonnative

    更新日期:2020-03-12
  • PIE-FLIM measurements of two different FRET-based biosensor activities in the same living cells
    Biophys. J. (IF 3.665) Pub Date : 2020-03-10
    Christopher A. Reissaus; Kathleen H. Day; Raghavendra G. Mirmira; Kenneth W. Dunn; Fredrick M. Pavalko; Richard N. Day

    We report the use of pulsed interleaved excitation-fluorescence lifetime imaging microscopy (PIE-FLIM) to measure the activities of two different biosensor probes simultaneously in single living cells. Many genetically encoded biosensors rely on the measurement of Förster resonance energy transfer (FRET) to detect changes in biosensor conformation that accompany the targeted cell signaling event. One

    更新日期:2020-03-12
  • The Poisson ratio of the cellular actin cortex is frequency-dependent
    Biophys. J. (IF 3.665) Pub Date : 2020-03-07
    M. Mokbel; K. Hosseini; S. Aland; E. Fischer-Friedrich

    Cell shape changes are vital for many physiological processes such as cell proliferation, cell migration and morphogenesis. They emerge from an orchestrated interplay of active cellular force generation and passive cellular force response - both crucially influenced by the actin cytoskeleton. To model cellular force response and deformation, cell mechanical models commonly describe the actin cytoskeleton

    更新日期:2020-03-09
  • Electrostatic environment of Proteorhodopsin affects the pKa of its buried primary proton acceptor
    Biophys. J. (IF 3.665) Pub Date : 2020-03-07
    Chung-Ta Han; Jichao Song; Tristan Chan; Christine Pruett; Songi Han

    The protonation state of embedded charged residues in transmembrane proteins (TMPs) can control the onset of protein function. It is understood that interactions between an embedded charged residue and other charged or polar residues in the moiety would influence its pKa, but how the surrounding environment in which the TMP resides affects the pKa of these residues is unclear. Proteorhodopsin (PR)

    更新日期:2020-03-09
  • Fundamental characteristics of neuron adhesion revealed by forced peeling and time-dependent healing
    Biophys. J. (IF 3.665) Pub Date : 2020-03-07
    Haipei Liu; Chao Fang; Ze Gong; Raymond Chuen-Chung Chang; Jin Qian; Huajian Gao; Yuan Lin

    A current bottleneck in the advance of neurophysics is the lack of reliable methods to quantitatively measure the interactions between neural cells and their microenvironment. Here, we present an experimental technique to probe the fundamental characteristics of neuron adhesion through repeated peeling of well-developed neurite branches on a substrate with an AFM cantilever. At the same time, a total

    更新日期:2020-03-09
  • Myosin II filament dynamics in actin networks revealed with interferometric scattering microscopy
    Biophys. J. (IF 3.665) Pub Date : 2020-03-04
    L.S. Mosby; N. Hundt; G. Young; A. Fineberg; M. Polin; S. Mayor; P. Kukura; D.V. Köster

    The plasma membrane and the underlying cytoskeletal cortex constitute active platforms for a variety of cellular processes. Recent work has shown that the remodeling acto-myosin network modifies local membrane organization, but the molecular details are only partly understood due to difficulties with experimentally accessing the relevant time and length scales. Here, we use interferometric scattering

    更新日期:2020-03-04
  • Exon definition facilitates reliable control of alternative splicing in the RON proto-oncogene
    Biophys. J. (IF 3.665) Pub Date : 2020-03-03
    Mihaela Enculescu; Simon Braun; Samarth Thonta Setty; Anke Busch; Kathi Zarnack; Julian König; Stefan Legewie

    Alternative splicing is a key step in eukaryotic gene expression that allows for the production of multiple transcript and protein isoforms from the same gene. Even though splicing is perturbed in many diseases, we currently lack insights into regulatory mechanisms promoting its precision and efficiency. We analyse high-throughput mutagenesis data obtained for an alternatively spliced exon in the proto-oncogene

    更新日期:2020-03-03
  • Kindlin Assists Talin to Promote Integrin Activation
    Biophys. J. (IF 3.665) Pub Date : 2020-03-03
    Zainab Haydari; Hengameh Shams; Zeinab Jahed; Mohammad R.K. Mofrad

    Integrin αIIbβ3 is a predominant type of integrin abundantly expressed on the surface of platelets and its activation regulates the process of thrombosis. Talin and kindlin are cytoplasmic proteins that bind to integrin and modulate its affinity for extracellular ligands. While the molecular details of talin-mediated integrin activation are known, the mechanism of kindlin involvement in this process

    更新日期:2020-03-03
  • Microrheology for Hi-C Data Reveals the Spectrum of the Dynamic 3D Genome Organization
    Biophys. J. (IF 3.665) Pub Date : 2020-03-03
    Soya Shinkai; Takeshi Sugawara; Hisashi Miura; Ichiro Hiratani; Shuichi Onami

    The 1-dimensional information of genomic DNA is hierarchically packed inside the eukaryotic cell nucleus and organized in 3-dimensional (3D) space. Genome-wide chromosome conformation capture (Hi-C) methods have uncovered the 3D genome organization and revealed multi-scale chromatin domains of compartments and topologically associating domains (TADs). Moreover, single-nucleosome live-cell imaging experiments

    更新日期:2020-03-03
  • What makes a good pore former: a Study of Synthetic Melittin Derivatives
    Biophys. J. (IF 3.665) Pub Date : 2020-03-03
    Aliasghar Sepehri; Leo PeBenito; Almudena Pino-Angeles; Themis Lazaridis

    Pore formation by membrane-active peptides, naturally encountered in innate immunity and infection, could have important medical and technological applications. Recently, the well-studied lytic peptide melittin has formed the basis for the development of combinatorial libraries, from which potent pore-forming peptides have been derived, optimized to work under different conditions. We investigate three

    更新日期:2020-03-03
  • Choice of force field for proteins containing structured and intrinsically disordered regions
    Biophys. J. (IF 3.665) Pub Date : 2020-02-29
    Vojtěch Zapletal; Arnošt Mládek; Kateřina Melková; Petr Louša; Erik Nomilner; Zuzana Jaseňáková; Vojtěch Kubáň; Markéta Makovická; Alice Laníková; Lukáš Žídek; Jozef Hritz

    Biomolecular force-fields optimized for globular proteins fail to properly reproduce properties of intrinsically disordered proteins (IDPs). In particular, parameters of the water model need to be modified in order to improve applicability of the force fields to both ordered and disordered proteins. Here we compared performance of force fields recommended for IDPs in molecular dynamics simulations

    更新日期:2020-03-02
  • Computing 3D chromatin configurations from contact probability maps by Inverse Brownian Dynamics
    Biophys. J. (IF 3.665) Pub Date : 2020-02-29
    Kiran Kumari; Burkhard Duenweg; Ranjith Padinhateeri; J. Ravi Prakash

    The three-dimensional organization of chromatin, on the length scale of a few genes, is crucial in determining the functional state — accessibility and the amount of gene expression — of the chromatin. Recent advances in chromosome conformation capture experiments provide partial information on the chromatin organization in a cell population, namely the contact count between any segment pairs, but

    更新日期:2020-03-02
  • Genome dashboards: Framework and Examples
    Biophys. J. (IF 3.665) Pub Date : 2020-02-29
    Z. Li; R. Sun; T.C. Bishop

    Genomics is a sequence-based informatics science and a 3D structure-based material science. However, in practice, most genomics researchers utilize sequence-based informatics approaches or 3D structure-based material science techniques, not both. This division is, at least in part, the result of historical developments rather than a fundamental necessity. The underlying computational tools, experimental

    更新日期:2020-03-02
  • Dynamics of the Buckling Transition in Double-Stranded DNA and RNA
    Biophys. J. (IF 3.665) Pub Date : 2020-02-29
    Katharina Ott; Linda Martini; Jan Lipfert; Ulrich Gerland

    DNA under torsional strain undergoes a buckling transition that is the fundamental step in plectoneme nucleation and supercoil dynamics, which are critical for the processing of genomic information. Despite its importance, quantitative models of the buckling transition, in particular also to explain the surprising two orders-of-magnitude difference between the buckling times for RNA and DNA revealed

    更新日期:2020-03-02
  • Spiral Wave Propagation in Communities with Spatially Correlated Heterogeneity.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-26
    Xiaoling Zhai,Joseph W Larkin,Gürol M Süel,Andrew Mugler

    Many multicellular communities propagate signals in a directed manner via excitable waves. Cell-to-cell heterogeneity is a ubiquitous feature of multicellular communities, but the effects of heterogeneity on wave propagation are still unclear. Here, we use a minimal FitzHugh-Nagumo-type model to investigate excitable wave propagation in a two-dimensional heterogeneous community. The model shows three

    更新日期:2020-02-27
  • An Electrophysiological Approach to Measure Changes in the Membrane Surface Potential in Real Time.
    Biophys. J. (IF 3.665) Pub Date : 2019-07-05
    Verena Burtscher,Matej Hotka,Michael Freissmuth,Walter Sandtner

    Biological membranes carry fixed charges at their surfaces. These arise primarily from phospholipid headgroups. In addition, membrane proteins contribute to the surface potential with their charged residues. Membrane lipids are asymmetrically distributed. Because of this asymmetry, the net-negative charge at the inner leaflet exceeds that at the outer leaflet. Changes in surface potential are predicted

    更新日期:2020-02-25
  • Processivity and Velocity for Motors Stepping on Periodic Tracks
    Biophys. J. (IF 3.665) Pub Date : 2020-02-25
    Mauro L. Mugnai; Matthew A. Caporizzo; Yale E. Goldman; D. Thirumalai

    Processive molecular motors enable cargo transportation by assembling into dimers capable of taking several consecutive steps along a cytoskeletal filament. In the well-accepted hand-over-hand stepping mechanism the trailing motor detaches from the track and binds the filament again in leading position. This requires fuel consumption in the form of ATP hydrolysis, and coordination of the catalytic

    更新日期:2020-02-25
  • Molecular Dynamics Ensemble Refinement of Intrinsically Disordered Peptides According to Deconvoluted Spectra from Circular Dichroism
    Biophys. J. (IF 3.665) Pub Date : 2020-02-25
    Jacob C. Ezerski; Pengzhi Zhang; Nathaniel C. Jennings; M. Neal Waxham; Margaret S. Cheung

    We have developed a computational method of atomistically refining the structural ensemble of intrinsically disorder peptides (IDPs) facilitated by experimental measurements using circular dichroism spectroscopy (CD). A major challenge surrounding this approach stems from the deconvolution of experimental CD spectra into secondary structure features of the IDP ensemble. Currently available algorithms

    更新日期:2020-02-25
  • Stochastic modeling of auto-regulatory genetic feedback loops: a review and comparative study
    Biophys. J. (IF 3.665) Pub Date : 2020-02-25
    J. Holehouse; Z. Cao; R. Grima

    Auto-regulatory feedback loops are one of the most common network motifs. A wide variety of stochastic models have been constructed to understand how the fluctuations in protein numbers in these loops are influenced by the kinetic parameters of the main biochemical steps. These models differ according to (i) which sub-cellular processes are explicitly modelled; (ii) the modelling methodology employed

    更新日期:2020-02-25
  • DNA unwinding dynamics of Escherichia coli UvrD lacking the C-terminal 40 amino acids
    Biophys. J. (IF 3.665) Pub Date : 2020-02-25
    Hiroaki Yokota

    The Escherichia coli UvrD protein is non-hexameric DNA helicase that belongs to superfamily I and plays a crucial role in both nucleotide-excision repair and methyl-directed mismatch repair. Previous data suggested that wild-type UvrD has optimal activity in its oligomeric form. However, crystal structures of the UvrD–DNA complex were only resolved for monomeric UvrD, using a UvrD mutant lacking the

    更新日期:2020-02-25
  • Predicting confined 1D cell migration from parameters calibrated to a 2D motor-clutch model
    Biophys. J. (IF 3.665) Pub Date : 2020-02-25
    Louis S. Prahl; Maria R. Stanslaski; Pablo Vargas; Matthieu Piel; David J. Odde

    Biological tissues contain micrometer-scale gaps and pores, including those found within extracellular matrix fiber networks, between tightly packed cells, and between blood vessels or nerve bundles and their associated basement membranes. These spaces restrict cell motion to a single spatial dimension (1D), a feature that is not captured in traditional in vitro cell migration assays performed on flat

    更新日期:2020-02-25
  • Pulsed Low Frequency Magnetic Fields Induce Tumor Membrane Disruption and Altered Cell Viability
    Biophys. J. (IF 3.665) Pub Date : 2020-02-18
    C.P. Ashdown; S.C. Johns; E. Aminov; M. Unanian; W. Connacher; J. Friend; M.M. Fuster

    Tumor cells express a unique cell-surface glycocalyx, with up-regulation of sulfated glycosaminoglycans and charged glycoproteins. Little is known about how electromagnetic fields interact with this layer, particularly with an eye to harness unique properties for therapeutic benefit. We applied a pulsed 20 mT magnetic field with rate of rise (dB/dt) in the msec range to cultured tumor cells to assess

    更新日期:2020-02-20
  • Modulation of toroidal proteins dynamics in favor of functional mechanisms upon ligand binding
    Biophys. J. (IF 3.665) Pub Date : 2020-02-18
    Hongchun Li; Pemra Doruker; Guang Hu; Ivet Bahar

    Toroidal proteins serve as molecular machines and play crucial roles in biological processes such as DNA replication and RNA transcription. Despite progress in the structural characterization of several toroidal proteins, we still lack a mechanistic understanding of the significance of their architecture, oligomerization states and intermolecular interactions in defining their biological function.

    更新日期:2020-02-20
  • Spatially Discordant Repolarization Alternans in the Absence of Conduction Velocity Restitution.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-15
    Chunli Huang,Zhen Song,Julian Landaw,Zhilin Qu

    Spatially discordant alternans (SDA) of action potential duration (APD) has been widely observed in cardiac tissue and is linked to cardiac arrhythmogenesis. Theoretical studies have shown that conduction velocity restitution (CVR) is required for the formation of SDA. However, this theory is not completely supported by experiments, indicating that other mechanisms may exist. In this study, we carried

    更新日期:2020-02-20
  • Facile Characterization of Topology of DNA Catenanes.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-15
    Lin Li,Ran An,Jiaxuan Tang,Zhe Sui,Guoqing Wang,Makoto Komiyama,Xingguo Liang

    During the preparation of single-stranded DNA catenanes, topological isomers of different linking numbers (Lk) are intrinsically produced, and they must be separated from each other to construct sophisticated nanostructures accurately. In many previous studies, however, mixtures of these isomers were directly employed to construct nanostructures without sufficient characterization. Here, we present

    更新日期:2020-02-20
  • Transcription Factor Binding in Embryonic Stem Cells Is Constrained by DNA Sequence Repeat Symmetry.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-15
    Matan Goldshtein,Meir Mellul,Gai Deutch,Masahiko Imashimizu,Koh Takeuchi,Eran Meshorer,Oren Ram,David B Lukatsky

    Transcription factor (TF) recognition is dictated by the underlying DNA motif sequence specific for each TF. Here, we reveal that DNA sequence repeat symmetry plays a central role in defining TF-DNA-binding preferences. In particular, we find that different TFs bind similar symmetry patterns in the context of different developmental layers. Most TFs possess dominant preferences for similar DNA repeat

    更新日期:2020-02-20
  • Stochastic model of T Cell repolarization during target elimination (I)
    Biophys. J. (IF 3.665) Pub Date : 2020-02-15
    Ivan Hornak; Heiko Rieger

    Cytotoxic T lymphocytes (T) and natural killer (NK) cells are the main cytotoxic killer cells of the human body to eliminate pathogen-infected or tumorigenic cells (i.e. target cells). Once a NK or T cell has identified a target cell, they form a tight contact zone, the immunological synapse (IS). One then observes a re-polarization of the cell involving the rotation of the microtubule (MT) cytoskeleton

    更新日期:2020-02-20
  • Interpretation of HDX Data by Maximum-Entropy Reweighting of Simulated Structural Ensembles.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-15
    Richard T Bradshaw,Fabrizio Marinelli,José D Faraldo-Gómez,Lucy R Forrest

    Hydrogen-deuterium exchange combined with mass spectrometry (HDX-MS) is a widely applied biophysical technique that probes the structure and dynamics of biomolecules without the need for site-directed modifications or bio-orthogonal labels. The mechanistic interpretation of HDX data, however, is often qualitative and subjective, owing to a lack of quantitative methods to rigorously translate observed

    更新日期:2020-02-20
  • Cell Fate Forecasting: A Data-Assimilation Approach to Predict Epithelial-Mesenchymal Transition.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-15
    Mario J Mendez,Matthew J Hoffman,Elizabeth M Cherry,Christopher A Lemmon,Seth H Weinberg

    Epithelial-mesenchymal transition (EMT) is a fundamental biological process that plays a central role in embryonic development, tissue regeneration, and cancer metastasis. Transforming growth factor-β (TGFβ) is a potent inducer of this cellular transition, which is composed of transitions from an epithelial state to intermediate or partial EMT state(s) to a mesenchymal state. Using computational models

    更新日期:2020-02-20
  • Recruitment of Ubiquitin within an E2 Chain Elongation Complex.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-15
    Benjamin W Cook,Rachel E Lacoursiere,Gary S Shaw

    The ubiquitin (Ub) proteolysis pathway uses an E1, E2, and E3 enzyme cascade to label substrate proteins with ubiquitin and target them for degradation. The mechanisms of ubiquitin chain formation remain unclear and include a sequential addition model, in which polyubiquitin chains are built unit by unit on the substrate, or a preassembly model, in which polyubiquitin chains are preformed on the E2

    更新日期:2020-02-20
  • Endothelial Glycocalyx Layer Properties and its Ability to Limit Leukocyte Adhesion
    Biophys. J. (IF 3.665) Pub Date : 2020-02-15
    Luis F. Delgadillo; Graham A. Marsh; Richard E. Waugh

    The endothelial glycocalyx layer (EGL), consisting of long proteoglycans protruding from the endothelium, acts as a regulator of inflammation by preventing leukocyte engagement with adhesion molecules on the endothelial surface. The amount of resistance to adhesive events the EGL provides is the result of two properties: EGL thickness and stiffness. To determine these, we used an atomic force microscope

    更新日期:2020-02-20
  • Biophysics of Membrane Protein Signaling.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-14
    Andrew Plested,Vasanthi Jayaraman

    更新日期:2020-02-14
  • Membrane Adhesion via Glycolipids Occurs for Abundant Saccharide Chemistries.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-12
    Victoria M Latza,Bruno Demé,Emanuel Schneck

    Membrane-bound oligosaccharides with specific chemistries are known to promote tight adhesion between adjacent membranes via the formation of weak saccharide bonds. However, in the literature, one can find scattered evidence that other, more abundant saccharide chemistries exhibit similar behavior. Here, the influence of various glycolipids on the interaction between adjacent membranes is systematically

    更新日期:2020-02-12
  • Coexistence of Lipid Phases Stabilizes Interstitial Water in the Outer Layer of Mammalian Skin.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-12
    Christopher M MacDermaid,Kyle Wm Hall,Russell H DeVane,Michael L Klein,Giacomo Fiorin

    The lipid matrix in the outer layer of mammalian skin, the stratum corneum, has been previously investigated by multiple biophysical techniques aimed at identifying hydrophilic and lipophilic pathways of permeation. Although consensus is developing over the microscopic structure of the lipid matrix, no molecular-resolution model describes the permeability of all chemical species simultaneously. Using

    更新日期:2020-02-12
  • Dissecting Particle Uptake Heterogeneity in a Cell Population Using Bayesian Analysis.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-12
    Md Shahinuzzaman,Dipak Barua

    Individual cells in a solution display variable uptake of nanomaterials, peptides, and nutrients. Such variability reflects their heterogeneity in endocytic capacity. In a recent work, we have shown that the endocytic capacity of a cell depends on its size and surface density of endocytic components (transporters). We also demonstrated that in MDA-MB-231 breast cancer cells, the cell-surface transporter

    更新日期:2020-02-12
  • Minimal Cylinder Analysis Reveals the Mechanical Properties of Oncogenic Nucleosomes.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-12
    Mary Pitman,Yamini Dalal,Garegin A Papoian

    Histone variants regulate replication, transcription, DNA damage repair, and chromosome segregation. Though widely accepted as a paradigm, it has not been rigorously demonstrated that histone variants encode unique mechanical properties. Here, we present a new theoretical approach called minimal cylinder analysis that uses strain fluctuations to determine the Young's modulus of nucleosomes from all-atom

    更新日期:2020-02-12
  • Probing Mechanisms of Transcription Elongation Through Cell-to-Cell Variability of RNA Polymerase.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-12
    Md Zulfikar Ali,Sandeep Choubey,Dipjyoti Das,Robert C Brewster

    The process of transcription initiation and elongation are primary points of control in the regulation of gene expression. Although biochemical studies have uncovered the mechanisms involved in controlling transcription at each step, how these mechanisms manifest in vivo at the level of individual genes is still unclear. Recent experimental advances have enabled single-cell measurements of RNA polymerase

    更新日期:2020-02-12
  • Conformational States Control Lck Switching between Free and Confined Diffusion Modes in T Cells.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-11
    Geva Hilzenrat,Elvis Pandžić,Zhengmin Yang,Daniel J Nieves,Jesse Goyette,Jérémie Rossy,Yuanqing Ma,Katharina Gaus

    T cell receptor phosphorylation by Lck is an essential step in T cell activation. It is known that the conformational states of Lck control enzymatic activity; however, the underlying principles of how Lck finds its substrate over the plasma membrane remain elusive. Here, single-particle tracking is paired with photoactivatable localization microscopy to observe the diffusive modes of Lck in the plasma

    更新日期:2020-02-11
  • Measuring Membrane Viscosity in the Widening Gyre.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-07
    Matthew C Blosser,Aurelia R Honerkamp-Smith

    The lipid membrane surrounding every living cell is a complex structure which has inspired decades of research into its biological functions and material properties. It might seem that a property of lipid membranes as fundamental as viscosity would be well-characterized and predictable. However, membrane viscosity has proven surprisingly challenging to measure. Approximate values and even relative

    更新日期:2020-02-07
  • Roles of Remote and Contact Forces in Epithelial Cell Structure Formation.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-05
    Tadashi Nakano,Yutaka Okaie,Yasuha Kinugasa,Takako Koujin,Tatsuya Suda,Yasushi Hiraoka,Tokuko Haraguchi

    Cancer cells collectively form a large-scale structure for their growth. In this article, we report that HeLa cells, epithelial-like human cervical cancer cells, aggressively migrate on Matrigel and form a large-scale structure in a cell-density-dependent manner. To explain the experimental results, we develop a simple model in which cells interact and migrate using the two fundamentally different

    更新日期:2020-02-06
  • Examining Go-or-Grow Using Fluorescent Cell-Cycle Indicators and Cell-Cycle-Inhibiting Drugs.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-05
    Sean T Vittadello,Scott W McCue,Gency Gunasingh,Nikolas K Haass,Matthew J Simpson

    The go-or-grow hypothesis states that adherent cells undergo reversible phenotype switching between migratory and proliferative states, with cells in the migratory state being more motile than cells in the proliferative state. Here, we examine go-or-grow in two-dimensional in vitro assays using melanoma cells with fluorescent cell-cycle indicators and cell-cycle-inhibiting drugs. We analyze the experimental

    更新日期:2020-02-06
  • Different Vinculin Binding Sites Use the Same Mechanism to Regulate Directional Force Transduction.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-04
    Carleen Kluger,Lukas Braun,Steffen M Sedlak,Diana A Pippig,Magnus S Bauer,Ken Miller,Lukas F Milles,Hermann E Gaub,Viola Vogel

    Vinculin is a universal adaptor protein that transiently reinforces the mechanical stability of adhesion complexes. It stabilizes mechanical connections that cells establish between the actomyosin cytoskeleton and the extracellular matrix via integrins or to neighboring cells via cadherins, yet little is known regarding its mechanical design. Vinculin binding sites (VBSs) from different nonhomologous

    更新日期:2020-02-06
  • Simple Rho GTPase Dynamics Generate a Complex Regulatory Landscape Associated with Cell Shape.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-04
    Cole Zmurchok,William R Holmes

    Migratory cells exhibit a variety of morphologically distinct responses to their environments that manifest in their cell shape. Some protrude uniformly to increase substrate contacts, others are broadly contractile, some polarize to facilitate migration, and yet others exhibit mixtures of these responses. Prior studies have identified a discrete collection of shapes that the majority of cells display

    更新日期:2020-02-06
  • The Interplay between Molten Globules and Heme Disassociation Defines Human Hemoglobin Disassembly.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-04
    Premila P Samuel,Mark A White,William C Ou,David A Case,George N Phillips,John S Olson

    Hemoglobin functions as a tetrameric oxygen transport protein, with each subunit containing a heme cofactor. Its denaturation, either in vivo or in vitro, involves autoxidation to methemoglobin, followed by cofactor loss and globin unfolding. We have proposed a global disassembly scheme for human methemoglobin, linking hemin (ferric protoporphyrin IX) disassociation and apoprotein unfolding pathways

    更新日期:2020-02-06
  • Chromatin Compaction Leads to a Preference for Peripheral Heterochromatin.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-04
    Quinn MacPherson,Bruno Beltran,Andrew J Spakowitz

    A layer of dense heterochromatin is found at the periphery of the nucleus. Because this peripheral heterochromatin functions as a repressive phase, mechanisms that relocate genes to the periphery play an important role in regulating transcription. Using Monte Carlo simulations, we show that an interaction that attracts euchromatin and heterochromatin equally to the nuclear envelope will still preferentially

    更新日期:2020-02-06
  • Partial Metal Ion Saturation of C2 Domains Primes Synaptotagmin 1-Membrane Interactions.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-04
    Sachin Katti,Sarah B Nyenhuis,Bin Her,David S Cafiso,Tatyana I Igumenova

    Synaptotagmin 1 (Syt1) is an integral membrane protein whose phospholipid-binding tandem C2 domains, C2A and C2B, act as Ca2+ sensors of neurotransmitter release. Our objective was to understand the role of individual metal-ion binding sites of these domains in the membrane association process. We used Pb2+, a structural and functional surrogate of Ca2+, to generate the protein states with well-defined

    更新日期:2020-02-06
  • How Nanopore Translocation Experiments Can Measure RNA Unfolding.
    Biophys. J. (IF 3.665) Pub Date : 2020-02-04
    Prasad Bandarkar,Huan Yang,Robert Y Henley,Meni Wanunu,Paul C Whitford

    Electrokinetic translocation of biomolecules through solid-state nanopores represents a label-free single-molecule technique that may be used to measure biomolecular structure and dynamics. Recent investigations have attempted to distinguish individual transfer RNA (tRNA) species based on the associated pore translocation times, ion-current noise, and blockage currents. By manufacturing sufficiently

    更新日期:2020-02-06
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