We present a mathematical model of membrane polarization in growth cones. We proceed by coupling an active transport model of cytosolic proteins along a two-dimensional microtubule (MT) network with a modified Dogterom-Leibler model of MT growth. In particular, we consider a Rac1-stathmin-MT pathway in which the growth and catastrophe rates of MTs are regulated by cytosolic stathmin, while the stathmin is regulated by Rac1 at the membrane. We use regular perturbation theory and numerical simulations to determine the steady-state stathmin concentration, the mean MT length distribution, and the resulting distribution of membrane-bound proteins.

Cell stiffness is a sensitive indicator of physiological and pathological changes in cells, with many potential applications in biology and medicine. A new method, real-time deformability cytometry, probes cell stiffness at high throughput by exposing cells to a shear flow in a microfluidic channel, allowing for mechanical phenotyping based on single-cell deformability. However, observed deformations of cells in the channel not only are determined by cell stiffness, but also depend on cell size relative to channel size.

Complex living systems such as mammalian cells can be arrested in a solid phase by ultrarapid cooling. This allows for precise observation of cellular structures as well as cryopreservation of cells. The state of water, the main constituent of biological samples, is crucial for the success of cryogenic applications. Water exhibits many different solid states. If it is cooled extremely rapidly, liquid water turns into amorphous ice, also called vitreous water, a glassy and amorphous solid. For cryo-preservation, the vitrification of cells is believed to be mandatory for cell survival after freezing.

Several bacterial and viral pathogens hijack the host actin cytoskeleton machinery to facilitate spread and infection. In particular, Listeria uses Arp2/3-mediated actin filament nucleation at the bacterial surface to generate a branched network that will help propel the bacteria. However, the mechanism of force generation remains elusive due to the lack of high-resolution three-dimensional structural data on the spatial organization of the actin mother and daughter (i.e., branch) filaments within this network.

2014. Cox, D. H. Modeling a Ca2+ Channel/BKCa Channel Complex at the Single-Complex Level. Biophys. J. 107:2797–2814.

The cornea is the primary refractive lens in the eye and transmits >90% of incident visible light. It has been suggested that the development of postoperative corneal haze could be due to an increase in light scattering from activated corneal stromal cells. Quiescent keratocytes are thought to produce crystallins that match the refractive index of their cytoplasm to the surrounding extracellular material, reducing the amount of light scattering. To test this, we measured the refractive index (RI) of bovine corneal stromal cells, using quantitative phase imaging of live cells in vitro, together with confocal microscopy.

Here, we propose two basic concepts that can streamline electrophysiology and imaging experiments in brain slices and enhance data collection and analysis. The first idea is to interface the experiment with a software environment that provides a 3D scene viewer in which the experimental rig, the brain slice, and the recorded data are represented to scale. Within the 3D scene viewer, the user can visualize a live image of the sample and 3D renderings of the recording electrodes with real-time position feedback.

We have investigated the role of electrostatic interactions in the transport of nucleic acids and ions through nanopores. The passage of DNA through nanopores has so far been conjectured to involve a free-energy barrier for entry, followed by a downhill translocation where the driving voltage accelerates the polymer. We have tested the validity of this conjecture by using two toxins, α-hemolysin and aerolysin, which differ in their shape, size, and charge. The characteristic timescales in each toxin as a function of temperature show that the entry barrier is ∼15kBT and the translocation barrier is ∼35kBT, although the electrical force in the latter step is much stronger.

While β-adrenergic receptor (β-AR) stimulation ensures adequate cardiac output during stress, it can also trigger life-threatening cardiac arrhythmias. We have previously shown that proarrhythmic Ca2+ waves during β-AR stimulation temporally coincide with augmentation of reactive oxygen species (ROS) production. In this study, we tested the hypothesis that increased energy demand during β-AR stimulation plays an important role in mitochondrial ROS production and Ca2+-wave generation in rabbit ventricular myocytes.

Kinetic hydrate inhibitors (KHIs) are used commercially to inhibit gas hydrate formation and growth in pipelines. However, improvement of these polymers has been constrained by the lack of verified molecular models. Since antifreeze proteins (AFPs) act as KHIs, we have used their solved x-ray crystallographic structures in molecular modeling to explore gas hydrate inhibition. The internal clathrate water network of the fish AFP Maxi, which extends to the protein’s outer surface, is remarkably similar to the {100} planes of structure type II (sII) gas hydrate.

Mammalian ceramides constitute a family of at least a few hundred closely related molecules distinguished by small structural differences, giving rise to individual molecular species that are expressed in distinct cellular compartments, or tissue types, in which they are believed to execute distinct functions. We have examined how specific structural details influence the bilayer properties of a selection of biologically relevant ceramides in mixed bilayers together with sphingomyelin, phosphatidylcholine, and cholesterol.

Intrinsically disordered proteins and intrinsically disordered regions are implicated in many biological functions and associated with many diseases, but their conformational characterizations are challenging. The disordered β6/β7 loop of Staphylococcus aureus sortase A is involved in the binding of both sorting signals and calcium. Calcium binding allosterically activates the enzyme, but the detailed mechanism has been unclear. Here we adapted the replica exchange with solute tempering method to sample the conformations of the β6/β7 loop, in apo form and in three liganded forms (bound with a sorting signal or calcium or both).

Cellular physical properties are important indicators of specific cell states. Although changes in individual biophysical parameters, such as cell size, density, and deformability, during cellular processes have been investigated in great detail, relatively little is known about how they are related. Here, we use a suspended microchannel resonator (SMR) to measure single-cell density, volume, and passage time through a narrow constriction of populations of cells subjected to a variety of environmental stresses.

Intrinsically disordered proteins (IDPs) are a fascinating class of newly recognized proteins that can exist as dynamic and heterogeneous ensembles of disordered structures under physiological conditions (1). They are highly prevalent in biology, frequently play crucial roles in cell signaling and regulation, and are associated with numerous human diseases (2). Many concepts have been proposed on how intrinsic conformational disorder may offer functional advantages, such as structural plasticity for binding multiple partners and inducibility by posttranslational modifications (3).

Viral terminase enzymes serve as genome packaging motors in many complex double-stranded DNA viruses. The functional motors are multiprotein complexes that translocate viral DNA into a capsid shell, powered by a packaging ATPase, and are among the most powerful molecular motors in nature. Given their essential role in virus development, the structure and function of these biological motors is of considerable interest. Bacteriophage λ-terminase, which serves as a prototypical genome packaging motor, is composed of one large catalytic subunit tightly associated with two DNA recognition subunits.

Endothelial cells are constantly exposed to fluid shear stresses that regulate vascular morphogenesis, homeostasis, and disease. The mechanical responses of endothelial cells to relatively high shear flow such as that characteristic of arterial circulation has been extensively studied. Much less is known about the responses of endothelial cells to slow shear flow such as that characteristic of venous circulation, early angiogenesis, atherosclerosis, intracranial aneurysm, or interstitial flow. Here we used a novel, to our knowledge, microfluidic technique to measure traction forces exerted by confluent vascular endothelial cell monolayers under slow shear flow.

Gene regulatory networks are multistable dynamical systems in which attractor states represent cell phenotypes. Spontaneous, noise-induced transitions between these states are thought to underlie critical cellular processes, including cell developmental fate decisions, phenotypic plasticity in fluctuating environments, and carcinogenesis. As such, there is increasing interest in the development of theoretical and computational approaches that can shed light on the dynamics of these stochastic state transitions in multistable gene networks.

Intracellular transport is essential for maintaining proper cellular function in most eukaryotic cells, with perturbations in active transport resulting in several types of disease. Efficient delivery of critical cargos to specific locations is accomplished through a combination of passive diffusion and active transport by molecular motors that ballistically move along a network of cytoskeletal filaments. Although motor-based transport is known to be necessary to overcome cytoplasmic crowding and the limited range of diffusion within reasonable timescales, the topological features of the cytoskeletal network that regulate transport efficiency and robustness have not been established.

The small GTP-binding proteins Arl2 and Arl3, which are close homologs, share a number of interacting partners and act as displacement factors for prenylated and myristoylated cargo. Nevertheless, both proteins have distinct biological functions. Whereas Arl3 is considered a ciliary protein, Arl2 has been reported to be involved in tubulin folding, mitochondrial function, and Ras signaling. How these different roles are attained by the two homolog proteins is not fully understood. Recently, we showed that the N-terminal amphipathic helix of Arl3, but not that of Arl2, regulates the release of myristoylated ciliary proteins from the GDI-like solubilizing factor UNC119a/b.

The presumptive function for alpha-tocopherol (αtoc) in membranes is to protect polyunsaturated lipids against oxidation. Although the chemistry of the process is well established, the role played by molecular structure that we address here with atomistic molecular-dynamics simulations remains controversial. The simulations were run in the constant particle NPT ensemble on hydrated lipid bilayers composed of SDPC (1-stearoyl-2-docosahexaenoylphosphatidylcholine, 18:0-22:6PC) and SOPC (1-stearoyl-2-oleoylphosphatidylcholine, 18:0-18:1PC) in the presence of 20 mol % αtoc at 37°C.