Dec 16, 2014

Volume 107Issue 12p2745-3044, L37-L48
Open Archive
Cover picture: A calcium “spark” ignites in a cardiac myocyte. The illustration shows calcium ions being released from a cluster of calcium-release channels (RyRs, green). The junctional sarcoplasmic reticulum is wrapped around a transverse tubule, forming a narrow subspace containing the RyR cluster. Walker et al. incorporate this geometry in a three-dimensional computational model to study spatiotemporal calcium dynamics in this microdomain. The model integrates realistic RyR clusters, such as the one here inferred from superresolution STED microscopy, and reveals how changes in RyR activity and junction morphology contribute to pathological calcium release in heart disease. For more information, see the article by Walker et al. on page 3018....
Cover picture: A calcium “spark” ignites in a cardiac myocyte. The illustration shows calcium ions being released from a cluster of calcium-release channels (RyRs, green). The junctional sarcoplasmic reticulum is wrapped around a transverse tubule, forming a narrow subspace containing the RyR cluster. Walker et al. incorporate this geometry in a three-dimensional computational model to study spatiotemporal calcium dynamics in this microdomain. The model integrates realistic RyR clusters, such as the one here inferred from superresolution STED microscopy, and reveals how changes in RyR activity and junction morphology contribute to pathological calcium release in heart disease. For more information, see the article by Walker et al. on page 3018.

Biophysical Letters

  • Biophysical Letter

    Dynamics of Cell Area and Force during Spreading

    • Yifat Brill-Karniely,
    • Noam Nisenholz,
    • Kavitha Rajendran,
    • Quynh Dang,
    • Ramaswamy Krishnan,
    • Assaf Zemel
    Experiments on human pulmonary artery endothelial cells are presented to show that cell area and the force exerted on a substrate increase simultaneously, but with different rates during spreading; rapid-force increase systematically occurred several minutes past initial spreading. We examine this theoretically and present three complementary mechanisms that may accompany the development of lamellar stress during spreading and underlie the observed behavior. These include: 1), the dynamics of cytoskeleton assembly at the cell basis; 2), the strengthening of acto-myosin forces in response to the generated lamellar stresses; and 3), the passive strain-stiffening of the cytoskeleton.
  • Biophysical Letter

    Inherent Force-Dependent Properties of β-Cardiac Myosin Contribute to the Force-Velocity Relationship of Cardiac Muscle

    • Michael J. Greenberg,
    • Henry Shuman,
    • E. Michael Ostap
    The heart adjusts its power output to meet specific physiological needs through the coordination of several mechanisms, including force-induced changes in contractility of the molecular motor, the β-cardiac myosin (βCM). Despite its importance in driving and regulating cardiac power output, the effect of force on the contractility of a single βCM has not been measured. Using single molecule optical-trapping techniques, we found that βCM has a two-step working stroke. Forces that resist the power stroke slow the myosin-driven contraction by slowing the rate of ADP release, which is the kinetic step that limits fiber shortening.
  • Biophysical Letter

    A GTPase Chimera Illustrates an Uncoupled Nucleotide Affinity and Release Rate, Providing Insight into the Activation Mechanism

    • Amy P. Guilfoyle,
    • Chandrika N. Deshpande,
    • Josep Font Sadurni,
    • Miriam-Rose Ash,
    • Samuel Tourle,
    • Gerhard Schenk,
    • Megan J. Maher,
    • Mika Jormakka
    The release of GDP from GTPases signals the initiation of a GTPase cycle, where the association of GTP triggers conformational changes promoting binding of downstream effector molecules. Studies have implicated the nucleotide-binding G5 loop to be involved in the GDP release mechanism. For example, biophysical studies on both the eukaryotic Gα proteins and the GTPase domain (NFeoB) of prokaryotic FeoB proteins have revealed conformational changes in the G5 loop that accompany nucleotide binding and release.

New and Notable

  • New and Notable

    Further Closing the Resolution Gap: Integrating Cryo-Soft X-Ray and Light Microscopies

    • Dorit Hanein
    Structural biologists are increasingly focused on the integration of micro-, meso-, and macroscale information to gain a comprehensive mechanistic understanding of dynamic biological processes. The last few years have witnessed a veritable quantum leap in our ability to perform imaging experiments on all resolution scales, including super-resolution light microscopies, a new generation of electron transmission microscopes, novel direct electron detectors, powerful scanning electron microscopes, and newly emerging soft x-ray microscopes.
  • New and Notable

    Lateral Exchange Smooths the Way for Vimentin Filaments

    • Laurent Kreplak,
    • Andrew D. Rutenberg
    Intermediate filaments (IFs), such as vimentin, do not assemble with end-directed addition of monomeric or dimeric subunits such as seen with filamentous actin or microtubules, respectively. Instead, IF assembly has been shown to involve short multisubunit unit-length filaments (ULFs) that assemble end-to-end (1). This first assembly step is well established in vitro for several proteins of the IF family (1). It is followed by a more elusive annealing process thought to involve tetramer exchange (2).
  • New and Notable

    The Ryanodine Receptor Patchwork: Knitting Calcium Spark Dynamics

    • Elisa Núñez-Acosta,
    • Eric A. Sobie
    Ca2+ sparks are microscopic (1–2 μm), probabilistic events that reflect release of Ca2+ from clusters of release channels, known as ryanodine receptors (RyRs), in the sarcoplasmic reticulum (SR) membrane. Although sparks have been observed in skeletal and smooth muscle, they have been most intensively studied in heart cells. Each cardiac Ca2+ spark reflects the stochastic gating of a cluster containing a relatively small number (10–100) of RyRs, and a typical ventricular myocyte may contain 10,000–20,000 of such RyR clusters, also known as Ca2+ release units (CRUs).

Biophysical Reviews

  • Biophysical Review

    Time-Resolved Fluorescence in Lipid Bilayers: Selected Applications and Advantages over Steady State

    • Mariana Amaro,
    • Radek Šachl,
    • Piotr Jurkiewicz,
    • Ana Coutinho,
    • Manuel Prieto,
    • Martin Hof
    Fluorescence methods are versatile tools for obtaining dynamic and topological information about biomembranes because the molecular interactions taking place in lipid membranes frequently occur on the same timescale as fluorescence emission. The fluorescence intensity decay, in particular, is a powerful reporter of the molecular environment of a fluorophore. The fluorescence lifetime can be sensitive to the local polarity, hydration, viscosity, and/or presence of fluorescence quenchers/energy acceptors within several nanometers of the vicinity of a fluorophore.
  • Biophysical Review

    Connecting the Dots: The Effects of Macromolecular Crowding on Cell Physiology

    • Márcio A. Mourão,
    • Joe B. Hakim,
    • Santiago Schnell
    The physicochemical properties of cellular environments with a high macromolecular content have been systematically characterized to explain differences observed in the diffusion coefficients, kinetics parameters, and thermodynamic properties of proteins inside and outside of cells. However, much less attention has been given to the effects of macromolecular crowding on cell physiology. Here, we review recent findings that shed some light on the role of crowding in various cellular processes, such as reduction of biochemical activities, structural reorganization of the cytoplasm, cytoplasm fluidity, and cellular dormancy.

Cell Biophysics

  • Article

    The Microtubule-Based Cytoskeleton Is a Component of a Mechanical Signaling Pathway in Fly Campaniform Receptors

    • Xin Liang,
    • Johnson Madrid,
    • Jonathon Howard
    In mechanoreceptors, mechanical stimulation by external forces leads to the rapid opening of transduction channels followed by an electrical response. Despite intensive studies in various model systems, the molecular pathway by which forces are transmitted to the transduction channels remains elusive. In fly campaniform mechanoreceptors, the mechanotransduction channels are gated by compressive forces conveyed via two rows of microtubules that are hypothesized to be mechanically reinforced by an intervening electron-dense material (EDM).
  • Article

    Mapping Diffusion in a Living Cell via the Phasor Approach

    • Suman Ranjit,
    • Luca Lanzano,
    • Enrico Gratton
    Diffusion of a fluorescent protein within a cell has been measured using either fluctuation-based techniques (fluorescence correlation spectroscopy (FCS) or raster-scan image correlation spectroscopy) or particle tracking. However, none of these methods enables us to measure the diffusion of the fluorescent particle at each pixel of the image. Measurement using conventional single-point FCS at every individual pixel results in continuous long exposure of the cell to the laser and eventual bleaching of the sample.

Channels and Transporters

  • Article

    Identification of a Cholesterol-Binding Pocket in Inward Rectifier K+ (Kir) Channels

    • Oliver Fürst,
    • Colin G. Nichols,
    • Guillaume Lamoureux,
    • Nazzareno D’Avanzo
    Cholesterol is the major sterol component of all mammalian plasma membranes. Recent studies have shown that cholesterol inhibits both bacterial (KirBac1.1 and KirBac3.1) and eukaryotic (Kir2.1) inward rectifier K+ (Kir) channels. Lipid-sterol interactions are not enantioselective, and the enantiomer of cholesterol (ent-cholesterol) does not inhibit Kir channel activity, suggesting that inhibition results from direct enantiospecific binding to the channel, and not indirect effects of changes to the bilayer.
  • Article

    Modeling a Ca2+ Channel/BKCa Channel Complex at the Single-Complex Level

    • Daniel H. Cox
    BKCa-channel activity often affects the firing properties of neurons, the shapes of neuronal action potentials (APs), and in some cases the extent of neurotransmitter release. It has become clear that BKCa channels often form complexes with voltage-gated Ca2+ channels (CaV channels) such that when a CaV channel is activated, the ensuing influx of Ca2+ activates its closely associated BKCa channel. Thus, in modeling the electrical properties of neurons, it would be useful to have quantitative models of CaV/BKCa complexes.
  • Retraction

    RETRACTED: Oxidative Stress and Ca2+ Release Events in Mouse Cardiomyocytes

    • Natalia Shirokova,
    • Chifei Kang,
    • Miguel Fernandez-Tenorio,
    • Wei Wang,
    • Qiongling Wang,
    • Xander H.T. Wehrens,
    • Ernst Niggli
    This article has been retracted: please see Elsevier Policy on Article Withdrawal ( ). This article has been retracted at the request of the Authors. After the publication of this paper, the authors became aware that data reported in several figures (Figs. 1, 2A, 3A, 4, and 5B) had been incorrectly analyzed and annotated. Some details about the solution protocol were also missing from the Materials and Methods section. These mistakes were unintentional.


  • Article

    High-Melting Lipid Mixtures and the Origin of Detergent-Resistant Membranes Studied with Temperature-Solubilization Diagrams

    • Jesús Sot,
    • Marco M. Manni,
    • Ana R. Viguera,
    • Verónica Castañeda,
    • Ainara Cano,
    • Cristina Alonso,
    • David Gil,
    • Mikel Valle,
    • Alicia Alonso,
    • Félix M. Goñi
    The origin of resistance to detergent solubilization in certain membranes, or membrane components, is not clearly understood. We have studied the solubilization by Triton X-100 of binary mixtures composed of egg sphingomyelin (SM) and either ceramide, diacylglycerol, or cholesterol. Solubilization has been assayed in the 4–50°C range, and the results are summarized in a novel, to our knowledge, form of plots, that we have called temperature-solubilization diagrams. Despite using a large detergent excess (lipid/detergent 1:20 mol ratio) and extended solubilization times (24–48 h) certain mixtures were not amenable to Triton X-100 solubilization at one or more temperatures.
  • Article

    PC12 Cells that Lack Synaptotagmin I Exhibit Loss of a Subpool of Small Dense Core Vesicles

    • Robert D. Adams,
    • Amy B. Harkins
    Neurons communicate by releasing neurotransmitters that are stored in intracellular vesicular compartments. PC12 cells are frequently used as a model secretory cell line that is described to have two subpools of vesicles: small clear vesicles and dense core vesicles. We measured transmitter molecules released from vesicles in NGF-differentiated PC12 cells using carbon-fiber amperometry, and relative diameters of individual vesicles using electron microscopy. Both amperometry and electron micrograph data were analyzed by statistical and machine learning methods for Gaussian mixture models.
  • Article

    Biophysical Properties of Novel 1-Deoxy-(Dihydro)ceramides Occurring in Mammalian Cells

    • Noemi Jiménez-Rojo,
    • Jesús Sot,
    • Jon V. Busto,
    • Walt A. Shaw,
    • Jingjing Duan,
    • Alfred H. Merrill Jr.,
    • Alicia Alonso,
    • Félix M. Goñi
    Ceramides and dihydroceramides are N-acyl derivatives of sphingosine and sphinganine, respectively, which are the major sphingoid-base backbones of mammals. Recent studies have found that mammals, like certain other organisms, also produce 1-deoxy-(dihydro)ceramides (1-deoxyDHCers) that contain sphingoid bases lacking the 1-hydroxyl- or 1-hydroxymethyl- groups. The amounts of these compounds can be substantial—indeed, we have found comparable levels of 1-deoxyDHCers and ceramides in RAW 264.7 cells maintained in culture.

Molecular Machines, Motors, and Nanoscale Biophysics

  • Article

    Feedback Mechanism for Microtubule Length Regulation by Stathmin Gradients

    • Maria Zeitz,
    • Jan Kierfeld
    We formulate and analyze a theoretical model for the regulation of microtubule (MT) polymerization dynamics by the signaling proteins Rac1 and stathmin. In cells, the MT growth rate is inhibited by cytosolic stathmin, which, in turn, is inactivated by Rac1. Growing MTs activate Rac1 at the cell edge, which closes a positive feedback loop. We investigate both tubulin sequestering and catastrophe promotion as mechanisms for MT growth inhibition by stathmin. For a homogeneous stathmin concentration in the absence of Rac1, we find a switchlike regulation of the MT mean length by stathmin.
  • Article

    The Motility of Axonemal Dynein Is Regulated by the Tubulin Code

    • Joshua D. Alper,
    • Franziska Decker,
    • Bernice Agana,
    • Jonathon Howard
    Microtubule diversity, arising from the utilization of different tubulin genes and from posttranslational modifications, regulates many cellular processes including cell division, neuronal differentiation and growth, and centriole assembly. In the case of cilia and flagella, multiple cell biological studies show that microtubule diversity is important for axonemal assembly and motility. However, it is not known whether microtubule diversity directly influences the activity of the axonemal dyneins, the motors that drive the beating of the axoneme, nor whether the effects on motility are indirect, perhaps through regulatory pathways upstream of the motors, such as the central pair, radial spokes, or dynein regulatory complex.
  • Article

    Capturing Transition Paths and Transition States for Conformational Rearrangements in the Ribosome

    • Jeffrey K. Noel,
    • Jorge Chahine,
    • Vitor B.P. Leite,
    • Paul Charles Whitford
    To reveal the molecular determinants of biological function, one seeks to characterize the interactions that are formed in conformational and chemical transition states. In other words, what interactions govern the molecule’s energy landscape? To accomplish this, it is necessary to determine which degrees of freedom can unambiguously identify each transition state. Here, we perform simulations of large-scale aminoacyl-transfer RNA (aa-tRNA) rearrangements during accommodation on the ribosome and project the dynamics along experimentally accessible atomic distances.
  • Article

    Role of Denatured-State Properties in Chaperonin Action Probed by Single-Molecule Spectroscopy

    • Hagen Hofmann,
    • Frank Hillger,
    • Cyrille Delley,
    • Armin Hoffmann,
    • Shawn H. Pfeil,
    • Daniel Nettels,
    • Everett A. Lipman,
    • Benjamin Schuler
    The bacterial chaperonin GroEL/GroES assists folding of a broad spectrum of denatured and misfolded proteins. Here, we explore the limits of this remarkable promiscuity by mapping two denatured proteins with very different conformational properties, rhodanese and cyclophilin A, during binding and encapsulation by GroEL/GroES with single-molecule spectroscopy, microfluidic mixing, and ensemble kinetics. We find that both proteins bind to GroEL with high affinity in a reaction involving substantial conformational adaptation.

Proteins and Nucleic Acids

  • Article

    The Structure of Misfolded Amyloidogenic Dimers: Computational Analysis of Force Spectroscopy Data

    • Yuliang Zhang,
    • Yuri L. Lyubchenko
    Progress in understanding the molecular mechanism of self-assembly of amyloidogenic proteins and peptides requires knowledge about their structure in misfolded states. Structural studies of amyloid aggregates formed during the early aggregation stage are very limited. Atomic force microscopy (AFM) spectroscopy is widely used to analyze misfolded proteins and peptides, but the structural characterization of transiently formed misfolded dimers is limited by the lack of computational approaches that allow direct comparison with AFM experiments.
  • Article

    The Role of Histone Tails in the Nucleosome: A Computational Study

    • Jochen Erler,
    • Ruihan Zhang,
    • Loukas Petridis,
    • Xiaolin Cheng,
    • Jeremy C. Smith,
    • Jörg Langowski
    Histone tails play an important role in gene transcription and expression. We present here a systematic computational study of the role of histone tails in the nucleosome, using replica exchange molecular dynamics simulations with an implicit solvent model and different well-established force fields. We performed simulations for all four histone tails, H4, H3, H2A, and H2B, isolated and with inclusion of the nucleosome. The results confirm predictions of previous theoretical studies for the secondary structure of the isolated tails but show a strong dependence on the force field used.
  • Article

    Direct Observation of Subunit Exchange along Mature Vimentin Intermediate Filaments

    • Bernd Nöding,
    • Harald Herrmann,
    • Sarah Köster
    Actin filaments, microtubules, and intermediate filaments (IFs) are central elements of the metazoan cytoskeleton. At the molecular level, the assembly mechanism for actin filaments and microtubules is fundamentally different from that of IFs. The former two types of filaments assemble from globular proteins. By contrast, IFs assemble from tetrameric complexes of extended, half-staggered, and antiparallel oriented coiled-coils. These tetramers laterally associate into unit-length filaments; subsequent longitudinal annealing of unit-length filaments yields mature IFs.
  • Article

    Characterization of the Conformational Fluctuations in the Josephin Domain of Ataxin-3

    • Domenico Sanfelice,
    • Alfonso De Simone,
    • Andrea Cavalli,
    • Serena Faggiano,
    • Michele Vendruscolo,
    • Annalisa Pastore
    As for a variety of other molecular recognition processes, conformational fluctuations play an important role in the cleavage of polyubiquitin chains by the Josephin domain of ataxin-3. The interaction between Josephin and ubiquitin appears to be mediated by the motions of α-helical hairpin that is unusual among deubiquitinating enzymes. Here, we characterized the conformational fluctuations of the helical hairpin by incorporating NMR measurements as replica-averaged restraints in molecular dynamics simulations, and by validating the results by small-angle x-ray scattering measurements.
  • Article

    The Kinetic Stability of Cytochrome c Oxidase: Effect of Bound Phospholipid and Dimerization

    • Erik Sedlák,
    • Rastislav Varhač,
    • Andrej Musatov,
    • Neal C. Robinson
    Thermally induced transitions of the 13-subunit integral membrane protein bovine cytochrome c oxidase (CcO) have been studied by differential scanning calorimetry (DSC) and circular dichroism (CD). Thermal denaturation of dodecyl maltoside solubilized CcO proceeds in two consecutive, irreversible, kinetically driven steps with the apparent transition temperatures at ∼ 51°C and ∼ 61°C (5μM CcO at scan rate of 1.5 K/min). The thermal denaturation data were analyzed according to the Lyubarev and Kurganov model of two consecutive irreversible steps.
  • Article

    Connecting Thermal and Mechanical Protein (Un)folding Landscapes

    • Li Sun,
    • Jeffrey K. Noel,
    • Joanna I. Sulkowska,
    • Herbert Levine,
    • José N. Onuchic
    Molecular dynamics simulations supplement single-molecule pulling experiments by providing the possibility of examining the full free energy landscape using many coordinates. Here, we use an all-atom structure-based model to study the force and temperature dependence of the unfolding of the protein filamin by applying force at both termini. The unfolding time-force relation τ(F) indicates that the force-induced unfolding behavior of filamin can be characterized into three regimes: barrier-limited low- and intermediate-force regimes, and a barrierless high-force regime.
  • Article

    Tetracycline Determines the Conformation of Its Aptamer at Physiological Magnesium Concentrations

    • Andreas J. Reuss,
    • Marc Vogel,
    • Julia E. Weigand,
    • Beatrix Suess,
    • Josef Wachtveitl
    Synthetic riboswitches are versatile tools for the study and manipulation of biological systems. Yet, the underlying mechanisms governing its structural properties and regulation under physiological conditions are poorly studied. We performed spectroscopic and calorimetric experiments to explore the folding kinetics and thermodynamics of the tetracycline-binding aptamer, which can be employed as synthetic riboswitch, in the range of physiological magnesium concentrations. The dissociation constant of the ligand-aptamer complex was found to strongly depend on the magnesium concentration.
  • Article

    Ligand Binding Modulates the Structural Dynamics and Compactness of the Major Birch Pollen Allergen

    • Sarina Grutsch,
    • Julian E. Fuchs,
    • Regina Freier,
    • Stefan Kofler,
    • Marium Bibi,
    • Claudia Asam,
    • Michael Wallner,
    • Fátima Ferreira,
    • Hans Brandstetter,
    • Klaus R. Liedl,
    • Martin Tollinger
    Pathogenesis-related plant proteins of class-10 (PR-10) are essential for storage and transport of small molecules. A prominent member of the PR-10 family, the major birch pollen allergen Bet v 1, is the main cause of spring pollinosis in the temperate climate zone of the northern hemisphere. Bet v 1 binds various ligand molecules to its internal cavity, and immunologic effects of the presence of ligand have been discussed. However, the mechanism of binding has remained elusive. In this study, we show that in solution Bet v 1.0101 is conformationally heterogeneous and cannot be represented by a single structure.
  • Article

    Exploring the Stability Limits of Actin and Its Suprastructures

    • Christopher Rosin,
    • Mirko Erlkamp,
    • Julian von der Ecken,
    • Stefan Raunser,
    • Roland Winter
    Actin is the main component of the microfilament system in eukaryotic cells and can be found in distinct morphological states. Global (G)-actin is able to assemble into highly organized, supramolecular cellular structures known as filamentous (F)-actin and bundled (B)-actin. To evaluate the structure and stability of G-, F-, and B-actin over a wide range of temperatures and pressures, we used Fourier transform infrared spectroscopy in combination with differential scanning and pressure perturbation calorimetry, small-angle x-ray scattering, laser confocal scanning microscopy, and transmission electron microscopy.

Systems Biophysics

  • Article

    A pH-Dependent Kinetic Model of Dihydrolipoamide Dehydrogenase from Multiple Organisms

    • Michael A. Moxley,
    • Daniel A. Beard,
    • Jason N. Bazil
    Dihydrolipoamide dehydrogenase is a flavoenzyme that reversibly catalyzes the oxidation of reduced lipoyl substrates with the reduction of NAD+ to NADH. In vivo, the dihydrolipoamide dehydrogenase component (E3) is associated with the pyruvate, α-ketoglutarate, and glycine dehydrogenase complexes. The pyruvate dehydrogenase (PDH) complex connects the glycolytic flux to the tricarboxylic acid cycle and is central to the regulation of primary metabolism. Regulation of PDH via regulation of the E3 component by the NAD+/NADH ratio represents one of the important physiological control mechanisms of PDH activity.
  • Article

    Residence Times of Receptors in Dendritic Spines Analyzed by Stochastic Simulations in Empirical Domains

    • Nathanael Hoze,
    • David Holcman
    Analysis of high-density superresolution imaging of receptors reveals the organization of dendrites at nanoscale resolution. We present here an apparently novel method that uses local statistics extracted from short-range trajectories for the simulations of long-range trajectories in empirical live cell images. Based on these empirical simulations, we compute the residence time of a receptor in dendritic spines that accounts for receptors’ local interactions and geometrical membrane organization.
  • Article

    Superresolution Modeling of Calcium Release in the Heart

    • Mark A. Walker,
    • George S.B. Williams,
    • Tobias Kohl,
    • Stephan E. Lehnart,
    • M. Saleet Jafri,
    • Joseph L. Greenstein,
    • W.J. Lederer,
    • Raimond L. Winslow
    Stable calcium-induced calcium release (CICR) is critical for maintaining normal cellular contraction during cardiac excitation-contraction coupling. The fundamental element of CICR in the heart is the calcium (Ca2+) spark, which arises from a cluster of ryanodine receptors (RyR). Opening of these RyR clusters is triggered to produce a local, regenerative release of Ca2+ from the sarcoplasmic reticulum (SR). The Ca2+ leak out of the SR is an important process for cellular Ca2+ management, and it is critically influenced by spark fidelity, i.e., the probability that a spontaneous RyR opening triggers a Ca2+ spark.
  • Article

    Nonlinear Compliance Modulates Dynamic Bronchoconstriction in a Multiscale Airway Model

    • Jonathan E. Hiorns,
    • Oliver E. Jensen,
    • Bindi S. Brook
    The role of breathing and deep inspirations (DI) in modulating airway hyperresponsiveness remains poorly understood. In particular, DIs are potent bronchodilators of constricted airways in nonasthmatic subjects but not in asthmatic subjects. Additionally, length fluctuations (mimicking DIs) have been shown to reduce mean contractile force when applied to airway smooth muscle (ASM) cells and tissue strips. However, these observations are not recapitulated on application of transmural pressure oscillations (that mimic tidal breathing and DIs) in isolated intact airways.


  • Correction


    2014. G. Arpağ, S. Shastry, W. O. Hancock, E. Tüzel. Transport by Populations of Fast and Slow Kinesins Uncovers Novel Family-Dependent Motor Characteristics Important for In Vivo Function. Biophys J. 107:1896–1904
  • Correction


    2014. Martin Aguilar, Xiao Yan Qi, Hai Huang, Philippe Comtois, and Stanley Nattel. Fibroblast Electrical Remodeling in Heart Failure and Potential Effects on Atrial Fibrillation. Biophys. J. 107: 2444–2455.
  • Correction


    2014. M. A. Angle, A. Wang, A. Thomas, A. T. Schaefer, and N. A. Melosh. Penetration of Cell Membranes and Synthetic Lipid Bilayers by Nanoprobes. Biophys. J. 107: 2091–2100.