Biophysical Journal

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Biophysical Journal RSS feed. Cell Press was chosen by the Biophysical Society to publish its premier journal, beginning in January 2009. Published semimonthly, the Biophysical Journal presents original articles, letters and reviews on the most important developments in modern biophysics, emphasizing the molecular and cellular aspects of biology.Topics covered include:Channels, Receptors, and Electrical SignalingProteins Biophysical Theory and ModelingCell BiophysicsPhotobiophysicsMembranesSpectroscopy, Imaging, Other TechniquesMuscle and ContractilitySupramolecular AssembliesBioenergeticsNucleic AcidsElectrophysiology
Updated: 9 weeks 6 days ago

Cell Mechanics: Combining Speed with Precision

Tue, 11/17/2015 - 00:00
The mechanical response of cells is a powerful biophysical marker for cell state. Information on a cell’s elasticity can, for instance, be used to distinguish between different cell phenotypes, or between healthy and diseased cells.
Categories: Journal Articles

High Spatiotemporal-Resolution Magnetic Tweezers: Calibration and Applications for DNA Dynamics

Tue, 11/17/2015 - 00:00
The observation of biological processes at the molecular scale in real time requires high spatial and temporal resolution. Magnetic tweezers are straightforward to implement, free of radiation or photodamage, and provide ample multiplexing capability, but their spatiotemporal resolution has lagged behind that of other single-molecule manipulation techniques, notably optical tweezers and AFM. Here, we present, to our knowledge, a new high-resolution magnetic tweezers apparatus. We systematically characterize the achievable spatiotemporal resolution for both incoherent and coherent light sources, different types and sizes of beads, and different types and lengths of tethered molecules.
Categories: Journal Articles

Nucleation: The Birth of a New Protein Phase

Tue, 11/17/2015 - 00:00
Nucleation is a process that initiates phase transitions. Since the classical work of Gibbs on nucleation thermodynamics at the end of the nineteenth century, research into nucleation processes has been spread into a huge variety of scientific fields. To date, nucleation has been studied in disciplines ranging from biophysics to cosmology in systems spanning atomic to planetary scales and beyond (1). Proteins in solution are also known historically to form a variety of states and structures through nucleation (2,3).
Categories: Journal Articles

Protein Polymerization into Fibrils from the Viewpoint of Nucleation Theory

Tue, 11/17/2015 - 00:00
The assembly of various proteins into fibrillar aggregates is an important phenomenon with wide implications ranging from human disease to nanoscience. Using general kinetic results of nucleation theory, we analyze the polymerization of protein into linear or helical fibrils in the framework of the Oosawa-Kasai (OK) model. We show that while within the original OK model of linear polymerization the process does not involve nucleation, within a modified OK model it is nucleation-mediated. Expressions are derived for the size of the fibril nucleus, the work for fibril formation, the nucleation barrier, the equilibrium and stationary fibril size distributions, and the stationary fibril nucleation rate.
Categories: Journal Articles

Insight into Early-Stage Unfolding of GPI-Anchored Human Prion Protein

Tue, 11/17/2015 - 00:00
Prion diseases are fatal neurodegenerative disorders, which are characterized by the accumulation of misfolded prion protein (PrPSc) converted from a normal host cellular prion protein (PrPC). Experimental studies suggest that PrPC is enriched with α-helical structure, whereas PrPSc contains a high proportion of β-sheet. In this study, we report the impact of N-glycosylation and the membrane on the secondary structure stability utilizing extensive microsecond molecular dynamics simulations. Our results reveal that the HB (residues 173 to 194) C-terminal fragment undergoes conformational changes and helix unfolding in the absence of membrane environments because of the competition between protein backbone intramolecular and protein-water intermolecular hydrogen bonds as well as its intrinsic instability originated from the amino acid sequence.
Categories: Journal Articles

CHARMM-GUI HMMM Builder for Membrane Simulations with the Highly Mobile Membrane-Mimetic Model

Tue, 11/17/2015 - 00:00
Slow diffusion of the lipids in conventional all-atom simulations of membrane systems makes it difficult to sample large rearrangements of lipids and protein-lipid interactions. Recently, Tajkhorshid and co-workers developed the highly mobile membrane-mimetic (HMMM) model with accelerated lipid motion by replacing the lipid tails with small organic molecules. The HMMM model provides accelerated lipid diffusion by one to two orders of magnitude, and is particularly useful in studying membrane-protein associations.
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Kymographic Imaging of the Elastic Modulus of Epithelial Cells during the Onset of Migration

Tue, 11/17/2015 - 00:00
Epithelial cell migration during wound repair involves a complex interplay of intracellular processes that enable motility while preserving contact among the cells. Recent evidence suggests that fluctuations of the intracellular biophysical state of cells generate traction forces at the basal side of the cells that are necessary for the cells to migrate. However, less is known about the biophysical and structural changes throughout the cells that accompany these fluctuations. Here, we utilized, to our knowledge, a novel kymographic nanoindentation method to obtain spatiotemporal measurements of the elastic moduli of living cells during migration after wounding.
Categories: Journal Articles

Bacteria Generate an Internal Mechanical Force within a Biofilm

Tue, 11/17/2015 - 00:00
A key issue in understanding why biofilms are the most prevalent mode of bacterial life is the origin of the degree of resistance and protection that bacteria gain from self-organizing into biofilm communities. Our experiments suggest that their mechanical properties are a key factor. Experiments on pellicles, or floating biofilms, of Bacillus subtilis showed that while they are multiplying and secreting extracellular substances, bacteria create an internal force (associated with a −80 ± 25 Pa stress) within the biofilms, similar to the forces that self-equilibrate and strengthen plants, organs, and some engineered buildings.
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Bacterial Motility Reveals Unknown Molecular Organization

Tue, 11/17/2015 - 00:00
The water solubility of lyotropic liquid crystals (LCs) makes them very attractive to study the behavior of biological microorganisms in an environment where local symmetry is broken (as often encountered in nature). Several recent studies have shown a dramatic change in the behavior of flagellated bacteria when swimming in solutions of the lyotropic LC disodium cromoglycate (DSCG). In this study, the movements of Escherichia coli bacteria in DSCG-water solutions of different concentrations are observed to improve our understanding of this phenomenon.
Categories: Journal Articles

Nanopore Sequencing: Forcing Improved Resolution

Tue, 11/17/2015 - 00:00
In 2012, nanopore DNA sequencing became a reality, with the publication of a proof-of-concept by the academic team led by Akeson and Gundlach (1) and the nearly simultaneous announcement (without publication) by Oxford Nanopore Technologies (Oxford Science Park, Oxford, UK) that the company had successfully sequenced DNA strands measuring tens of kilobases in length using nanopore technology (2). Nanopore sequencing has great technological potential because it is a single-molecule technique, there is no upper limit to the length of DNA that can be sequenced, and the electrical sensing mechanism can be massively parallelized on a chip.
Categories: Journal Articles

Mechanistic Insights into the Modulation of Voltage-Gated Ion Channels by Inhalational Anesthetics

Tue, 11/17/2015 - 00:00
General anesthesia is a relatively safe medical procedure, which for nearly 170 years has allowed life saving surgical interventions in animals and people. However, the molecular mechanism of general anesthesia continues to be a matter of importance and debate. A favored hypothesis proposes that general anesthesia results from direct multisite interactions with multiple and diverse ion channels in the brain. Neurotransmitter-gated ion channels and two-pore K+ channels are key players in the mechanism of anesthesia; however, new studies have also implicated voltage-gated ion channels.
Categories: Journal Articles

Modeling Local X-ROS and Calcium Signaling in the Heart

Tue, 11/17/2015 - 00:00
Stretching single ventricular cardiac myocytes has been shown experimentally to activate transmembrane nicotinamide adenine dinucleotide phosphate oxidase type 2 to produce reactive oxygen species (ROS) and increase the Ca2+ spark rate in a process called X-ROS signaling. The increase in Ca2+ spark rate is thought to be due to an increase in ryanodine receptor type 2 (RyR2) open probability by direct oxidation of the RyR2 protein complex. In this article, a computational model is used to examine the regulation of ROS and calcium homeostasis by local, subcellular X-ROS signaling and its role in cardiac excitation-contraction coupling.
Categories: Journal Articles

Diffusion Regulation in the Vitreous Humor

Tue, 11/17/2015 - 00:00
The efficient treatment of many ocular diseases depends on the rapid diffusive distribution of solutes such as drugs or drug delivery vehicles through the vitreous humor. However, this multicomponent hydrogel possesses selective permeability properties, which allow for the diffusion of certain molecules and particles, whereas others are immobilized. In this study, we perform an interspecies comparison showing that the selective permeability properties of the vitreous are conserved across several mammalian species.
Categories: Journal Articles

Contributions of Ca-Independent Thin Filament Activation to Cardiac Muscle Function

Tue, 11/17/2015 - 00:00
Although Ca2+ is the principal regulator of contraction in striated muscle, in vitro evidence suggests that some actin-myosin interaction is still possible even in its absence. Whether this Ca2+-independent activation (CIA) occurs under physiological conditions remains unclear, as does its potential impact on the function of intact cardiac muscle. The purpose of this study was to investigate CIA using computational analysis. We added a structurally motivated representation of this phenomenon to an existing myofilament model, which allowed predictions of CIA-dependent muscle behavior.
Categories: Journal Articles

Coupling Controls the Synchrony of Clock Cells in Development and Knockouts

Tue, 11/17/2015 - 00:00
In mammals, a network of coupled neurons within the hypothalamus coordinates physiological rhythms with daily changes in the environment. In each neuron, delayed negative transcriptional feedbacks generate oscillations, albeit noisy and unreliable ones. Coupling mediated by diffusible neuropeptides lends precision and robustness to circadian rhythms. The double knockout of Cryptochrome Cry turns adult mice arrhythmic. But, remarkably, double knockout neonates continue to show robust oscillation much like wild-type neonates and appear to lose rhythmicity with development.
Categories: Journal Articles

Interpreting Heterogeneity in Response of Cells Expressing a Fluorescent Hydrogen Peroxide Biosensor

Tue, 11/17/2015 - 00:00
Fluorescent, genetically encoded sensors of hydrogen peroxide have enabled visualization of perturbations to the intracellular level of this signaling molecule with subcellular and temporal resolution. Ratiometric sensors hold the additional promise of meaningful quantification of intracellular hydrogen peroxide levels as a function of time, a longstanding goal in the field of redox signaling. To date, studies that have connected the magnitudes of observed ratios with peroxide concentrations have either examined suspensions of cells or small numbers of adherent cells (∼10).
Categories: Journal Articles

Ellipsoid Localization Microscopy Infers the Size and Order of Protein Layers in Spore Coats

Tue, 11/17/2015 - 00:00
Multilayered protein coats are crucial to the dormancy, robustness, and germination of bacterial spores. In Bacillus subtilis spores, the coat contains over 70 distinct proteins. Identifying which proteins reside in each layer may provide insight into their distinct functions. We present image analysis methods that determine the order and geometry of concentric protein layers by fitting a model description for a spheroidal fluorescent shell image to optical micrographs of spores incorporating fluorescent fusion proteins.
Categories: Journal Articles

The Molecular Mechanism Underlying Recruitment and Insertion of Lipid-Anchored LC3 Protein into Membranes

Tue, 11/17/2015 - 00:00
Lipid modification of cytoplasmic proteins initiates membrane engagement that triggers diverse cellular processes. Despite the abundance of lipidated proteins in the human proteome, the key determinants underlying membrane recognition and insertion are poorly understood. Here, we define the course of spontaneous membrane insertion of LC3 protein modified with phosphatidylethanolamine using multiple coarse-grain simulations. The partitioning of the lipid anchor chains proceeds through a concerted process, with its two acyl chains inserting one after the other.
Categories: Journal Articles

Vesicle Leakage Reflects the Target Selectivity of Antimicrobial Lipopeptides from

Tue, 11/17/2015 - 00:00
Cyclic lipopeptides act against a variety of plant pathogens and are thus highly efficient crop-protection agents. Some pesticides contain Bacillus subtilis strains that produce lipopeptide families, such as surfactins (SF), iturins (IT), and fengycins (FE). The antimicrobial activity of these peptides is mainly mediated by permeabilizing cellular membranes. We used a fluorescence-lifetime based leakage assay to examine the effect of individual lipid components in model membranes on lipopeptide activity.
Categories: Journal Articles

Colocalization and Sequential Enzyme Activity in Aqueous Biphasic Systems: Experiments and Modeling

Tue, 11/17/2015 - 00:00
Subcellular compartmentalization of biomolecules and their reactions is common in biology and provides a general strategy for improving and/or controlling kinetics in metabolic pathways that contain multiple sequential enzymes. Enzymes can be colocalized in multiprotein complexes, on scaffolds or inside subcellular organelles. Liquid organelles formed by intracellular phase coexistence could provide an additional means of sequential enzyme colocalization. Here we use experiment and computation to explore the kinetic consequences of sequential enzyme compartmentalization into model liquid organelles in a crowded polymer solution.
Categories: Journal Articles