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Biophysical Journal

Krishnan Raghunathan, Tiffany H Wong, Daniel J Chinnapen, Wayne I Lencer, Michael G Jobling, Anne K Kenworthy
Current models of lipid rafts propose that lipid domains exist as nanoscale compositional fluctuations and these fluctuations can potentially be stabilized into larger domains, consequently better compartmentalizing cellular functions. However, the mechanisms governing stabilized raft assembly and function remain unclear. Here, we test the role of glycolipid crosslinking as a raft targeting and ordering mechanism using the well-studied raft marker cholera toxin B pentamer (CTxB) that binds up to five GM1 glycosphingolipids to enter host cells...
November 30, 2016: Biophysical Journal
Karin Halbmair, Janine Wegner, Ulf Diederichsen, Marina Bennati
We present the performance of nanometer-range pulse electron paramagnetic resonance distance measurements (pulsed electron-electron double resonance/double electron-electron resonance, PELDOR/DEER) on a transmembrane WALP24 peptide labeled with the semirigid unnatural amino acid 4-(3,3,5,5-tetra-methyl-2,6-dioxo-4-oxylpiperazin-1-yl)-l-phenylglycine (TOPP). Distances reported by the TOPP label are compared to the ones reported by the more standard MTSSL spin label, commonly employed in protein studies. Using high-power pulse electron paramagnetic resonance spectroscopy at Q-band frequencies (34 GHz), we show that in contrast to MTSSL, our label reports one-peak, sharp (Δr ≤ 0...
November 8, 2016: 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.
September 30, 2016: 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...
September 27, 2016: Biophysical Journal
Brittny C Davis, Jodian A Brown, Ian F Thorpe
No abstract text is available yet for this article.
November 15, 2016: Biophysical Journal
Graham M Donovan
Airway closure has important implications for lung disease, especially asthma; in particular, the prospect of bistability between open and closed (or effectively closed) airway states has been thought to play a prominent role in airway closure associated with the formation of clustered ventilation defects in asthma. However, many existing analyses of closure consider only static airway equilibria; here we construct, to our knowledge, a new model wherein airway narrowing and closure dynamics are modulated by coupling the airway to cross-bridge models of airway smooth muscle dynamics and force generation...
November 15, 2016: Biophysical Journal
Sean D Lawley, James P Keener
The behavior of biochemical reactions requiring repeated enzymatic substrate modification depends critically on whether the enzymes act processively or distributively. Whereas processive enzymes bind only once to a substrate before carrying out a sequence of modifications, distributive enzymes release the substrate after each modification and thus require repeated bindings. Recent experimental and computational studies have revealed that distributive enzymes can act processively due to rapid rebindings (so-called quasi-processivity)...
November 15, 2016: Biophysical Journal
Qian Zhu, Fan Zheng, Allen P Liu, Jin Qian, Chuanhai Fu, Yuan Lin
The nuclear envelope (NE) in lower eukaryotes such as Schizosaccharomyces pombe undergoes large morphology changes during closed mitosis. However, which physical parameters are important in governing the shape evolution of the NE, and how defects in the dividing chromosomes/microtubules are reflected in those parameters, are fundamental questions that remain unresolved. In this study, we show that improper separation of chromosomes in genetically deficient cells leads to membrane tethering or asymmetric division in contrast to the formation of two equal-sized daughter nuclei in wild-type cells...
November 15, 2016: Biophysical Journal
Sungmin Nam, Joanna Lee, Doug G Brownfield, Ovijit Chaudhuri
Living tissues consist largely of cells and extracellular matrices (ECMs). The mechanical properties of ECM have been found to play a key role in regulating cell behaviors such as migration, proliferation, and differentiation. Although most studies to date have focused on elucidating the impact of matrix elasticity on cell behaviors, recent studies have revealed an impact of matrix viscoelasticity on cell behaviors and reported plastic remodeling of ECM by cells. In this study, we rigorously characterized the plasticity in materials commonly used for cell culture...
November 15, 2016: Biophysical Journal
Tomo Murovec, Daniel C Sweeney, Eduardo Latouche, Rafael V Davalos, Christian Brosseau
Many approaches for studying the transmembrane potential (TMP) induced during the treatment of biological cells with pulsed electric fields have been reported. From the simple analytical models to more complex numerical models requiring significant computational resources, a gamut of methods have been used to recapitulate multicellular environments in silico. Cells have been modeled as simple shapes in two dimensions as well as more complex geometries attempting to replicate realistic cell shapes. In this study, we describe a method for extracting realistic cell morphologies from fluorescence microscopy images to generate the piecewise continuous mesh used to develop a finite element model in two dimensions...
November 15, 2016: Biophysical Journal
Tommaso Ristori, Andrea Vigliotti, Frank P T Baaijens, Sandra Loerakker, Vikram S Deshpande
Cells respond to both mechanical and topographical stimuli by reorienting and reorganizing their cytoskeleton. Under certain conditions, such as for cells on cyclically stretched grooved substrates, the effects of these stimuli can be antagonistic. The biophysical processes that lead to the cellular reorientation resulting from such a competition are not clear yet. In this study, we hypothesized that mechanical cues and the diffusion of the intracellular signal produced by focal adhesions are determinants of the final cellular alignment...
November 15, 2016: Biophysical Journal
Hendrick W de Haan
Bacteria such as Pseudomonas aeruginosa use type IV pili to move across surfaces. The pili extend, attach to the surface, and then retract to move the bacteria forward. In this article, a coarse-grained model of pilus extension and attachment is developed. Simulations performed at biologically relevant conditions indicate that pilus extension is a quasistatic process such that the pili are able to relax via thermal fluctuations as it is being built and extended. Results are generated for pili with different rigidities ranging from very flexible to very stiff...
November 15, 2016: Biophysical Journal
Takanori Iino, Man Hagiyama, Tadahide Furuno, Akihiko Ito, Yoichiroh Hosokawa
The maturation of intercellular adhesion is an essential process for establishing the signal transduction network in living cells. Although the maturation is naturally considered to enhance the signal transduction, the relationship between the signal transduction and the maturation process has not been revealed in detail using time-course data. Here, using a coculture of mast cells and neurites, differences in maturation between individual cells were estimated as a function of the adhesion strength by our original single-cell measurement method utilizing a laser-induced impulsive force...
November 15, 2016: Biophysical Journal
Sibel Yavas, Radek Macháň, Thorsten Wohland
The epidermal growth factor receptor (EGFR) is a prototypical receptor tyrosine kinase involved in cell growth and proliferation and associated with various cancers. It is commonly assumed that after activation by binding of epidermal growth factor to the extracellular domain it dimerizes, followed by autophosphorylation of tyrosine residues at the intracellular domain. However, its oligomerization state before activation is controversial. In the absence of ligands, EGFR has been found in various, inconsistent amounts of monomeric, inactive dimeric, and oligomeric forms...
November 15, 2016: Biophysical Journal
M Yusuf Ali, Andrej Vilfan, Kathleen M Trybus, David M Warshaw
Myosin Va (myoVa) is a processive, actin-based molecular motor essential for intracellular cargo transport. When a cargo is transported by an ensemble of myoVa motors, each motor faces significant physical barriers and directional challenges created by the complex actin cytoskeleton, a network of actin filaments and actin bundles. The principles that govern the interaction of multiple motors attached to the same cargo are still poorly understood. To understand the mechanical interactions between multiple motors, we developed a simple in vitro model in which two individual myoVa motors labeled with different-colored Qdots are linked via a third Qdot that acts as a cargo...
November 15, 2016: Biophysical Journal
Yen-Liang Liu, Evan P Perillo, Cong Liu, Peter Yu, Chao-Kai Chou, Mien-Chie Hung, Andrew K Dunn, Hsin-Chih Yeh
Whereas important discoveries made by single-particle tracking have changed our view of the plasma membrane organization and motor protein dynamics in the past three decades, experimental studies of intracellular processes using single-particle tracking are rather scarce because of the lack of three-dimensional (3D) tracking capacity. In this study we use a newly developed 3D single-particle tracking method termed TSUNAMI (Tracking of Single particles Using Nonlinear And Multiplexed Illumination) to investigate epidermal growth factor receptor (EGFR) trafficking dynamics in live cells at 16/43 nm (xy/z) spatial resolution, with track duration ranging from 2 to 10 min and vertical tracking depth up to tens of microns...
November 15, 2016: Biophysical Journal
Valerie C Coffman, Torah M Kachur, David B Pilgrim, Adriana T Dawes
Contractile rings play critical roles in a number of biological processes, including oogenesis, wound healing, and cytokinesis. In many cases, the activity of motor proteins such as nonmuscle myosins is required for appropriate constriction of these contractile rings. In the gonad of the nematode worm Caenorhabditis elegans, ring channels are a specialized form of contractile ring that are maintained at a constant diameter before oogenesis. We propose a model of ring channel maintenance that explicitly incorporates force generation by motor proteins that can act normally or tangentially to the ring channel opening...
November 15, 2016: Biophysical Journal
Sayed Ul Alam Shibly, Chiranjib Ghatak, Mohammad Abu Sayem Karal, Md Moniruzzaman, Masahito Yamazaki
Osmotic pressure (Π) induces the stretching of plasma membranes of cells or lipid membranes of vesicles, which plays various roles in physiological functions. However, there have been no experimental estimations of the membrane tension of vesicles upon exposure to Π. In this report, we estimated experimentally the lateral tension of the membranes of giant unilamellar vesicles (GUVs) when they were transferred into a hypotonic solution. First, we investigated the effect of Π on the rate constant, kp, of constant-tension (σex)-induced rupture of dioleoylphosphatidylcholine (DOPC)-GUVs using the method developed by us recently...
November 15, 2016: Biophysical Journal
J Michael Henderson, Alan J Waring, Frances Separovic, Ka Yee C Lee
Antimicrobial peptides (AMPs) are a class of host-defense molecules that neutralize a broad range of pathogens. Their membrane-permeabilizing behavior has been commonly attributed to the formation of pores; however, with the continuing discovery of AMPs, many are uncharacterized and their exact mechanism remains unknown. Using atomic force microscopy, we previously characterized the disruption of model membranes by protegrin-1 (PG-1), a cationic AMP from pig leukocytes. When incubated with zwitterionic membranes of dimyristoylphosphocholine, PG-1 first induced edge instability at low concentrations, then porous defects at intermediate concentrations, and finally worm-like micelle structures at high concentrations...
November 15, 2016: Biophysical Journal
Martin Rabe, Christopher Aisenbrey, Kristyna Pluhackova, Vincent de Wert, Aimee L Boyle, Didjay F Bruggeman, Sonja A Kirsch, Rainer A Böckmann, Alexander Kros, Jan Raap, Burkhard Bechinger
A system based on two designed peptides, namely the cationic peptide K, (KIAALKE)3, and its complementary anionic counterpart called peptide E, (EIAALEK)3, has been used as a minimal model for membrane fusion, inspired by SNARE proteins. Although the fact that docking of separate vesicle populations via the formation of a dimeric E/K coiled-coil complex can be rationalized, the reasons for the peptides promoting fusion of vesicles cannot be fully explained. Therefore it is of significant interest to determine how the peptides aid in overcoming energetic barriers during lipid rearrangements leading to fusion...
November 15, 2016: Biophysical Journal
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