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At least 775 records · Page 43Linked to original sources
arXiv2006

A Chemical Kinetic Model of Transcriptional Elongation

A chemical kinetic model of the elongation dynamics of RNA polymerase along a DNA sequence is introduced. The proposed model governs the discrete movement of the RNA polymerase along a DNA template, with no consideration given to elastic effects. The model's novel concept is a ``look-ahead'' feature, in which nucleotides bind reversibly to the DNA prior to being incorporated covalently into the nascent RNA chain. Results are presented for specific DNA sequences that have been used in single-molecule experiments of the random walk of RNA polymerase along DNA. By replicating the data analysis algorithm from the experimental procedure, the model produces velocity histograms, enabling direct comparison with these published results.

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arXiv2006

The Water Circuit of the Plants - Do Plants have Hearts ?

There is a correspondence between the circulation of blood in all higher animals and the circulation of sap in all higher plants - up to heights h of 140 m - through the xylem and phloem vessels. Plants suck in water from the soil, osmotically through the roothair zone, and subsequently lift it osmotically again, and by capillary suction (via their buds, leaves, and fruits) into their crowns. In between happens a reverse osmosis - the endodermis jump - realized by two layers of subcellular mechanical pumps in the endodermis walls which are powered by ATP, or in addition by two analogous layers of such pumps in the exodermis. The thus established root pressure helps forcing the absorbed ground water upward, through the whole plant, and often out again, in the form of guttation, or exudation.

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arXiv2006

Dynamic stability of spindles controlled by molecular motor kinetics

We analyze the role of the force-dependent kinetics of motor proteins in the stability of antiparallel arrays of polar filaments, such as those in the mitotic spindle. We determine the possible stable structures and show that there exists an instability associated to the collective behavior of motors that leads to the collapse of the spindle. Our analysis provides a general framework to understand several experimental observations in eukaryotic cell division.

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arXiv2011

A Surprising Clarification of the Mechanism of Ion-channel Voltage-Gating

An intense controversy has surrounded the mechanism of voltage-gating in ion channels. We interpreted the two leading models of voltage-gating with respect to the thermodynamic energetics of membrane insertion of the voltage-sensing 'module' from a comprehensive set of potassium channels. KvAP is an archaeal voltage-gated potassium channel whose x-ray structure was the basis for determining the general mechanism of voltage-gating. The free energy of membrane insertion of the KvAP voltage sensor was revealed to be a single outlier. This was due to its unusual sequence that facilitated large gating movements in its native lipid membrane. This degree of free energy was the least typical of the other voltage sensors, including the Shaker potassium channel. We inferred that the two leading models of voltage-gating referred to alternative mechanisms of voltage-gating: each is applicable to an independent set of ion channels. The large motion of the voltage-sensor during gating proposed by the KvAP-paddle model of gating is unlikely to be mirrored by the majority of ion channels whose voltage sensors are not located at the membrane-cytoplasm interface in the channel closed state.

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arXiv2008

How T-cells use large deviations to recognize foreign antigens

A stochastic model for the activation of T-cells is analysed. T-cells are part of the immune system and recognize foreign antigens against a background of the body's own molecules. The model under consideration is a slight generalization of a model introduced by Van den Berg, Rand and Burroughs in 2001, and is capable of explaining how this recognition works on the basis of rare stochastic events. With the help of a refined large deviation theorem and numerical evaluation it is shown that, for a wide range of parameters, T-cells can distinguish reliably between foreign antigens and self-antigens.

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arXiv2006

Topological classification of RNA structures

We present a novel topological classification of RNA secondary structures with pseudoknots. It is based on the topological genus of the circular diagram associated to the RNA base-pair structure. The genus is a positive integer number, whose value quantifies the topological complexity of the folded RNA structure. In such a representation, planar diagrams correspond to pure RNA secondary structures and have zero genus, whereas non planar diagrams correspond to pseudoknotted structures and have higher genus. We analyze real RNA structures from the databases wwPDB and Pseudobase, and classify them according to their topological genus. We compare the results of our statistical survey with existing theoretical and numerical models. We also discuss possible applications of this classification and show how it can be used for identifying new RNA structural motifs.

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arXiv2006

Focal adhesions as mechanosensors: the two-spring model

Adhesion-dependent cells actively sense the mechanical properties of their environment through mechanotransductory processes at focal adhesions, which are integrin-based contacts connecting the extracellular matrix to the cytoskeleton. Here we present first steps towards a quantitative understanding of focal adhesions as mechanosensors. It has been shown experimentally that high levels of force are related to growth of and signaling at focal adhesions. In particular, activation of the small GTPase Rho through focal adhesions leads to the formation of stress fibers. Here we discuss one way in which force might regulate the internal state of focal adhesions, namely by modulating the internal rupture dynamics of focal adhesions. A simple two-spring model shows that the stiffer the environment, the more efficient cellular force is built up at focal adhesions by molecular motors interacting with the actin filaments.

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arXiv2008

Genotype-based Case-Control Analysis, Violation of Hardy-Weinberg Equilibrium, and Phase Diagrams

We study in detail a particular statistical method in genetic case-control analysis, labeled "genotype-based association", in which the two test results from assuming dominant and recessive model are combined in one optimal output. This method differs both from the allele-based association which artificially doubles the sample size, and the direct chi-square test on 3-by-2 contingency table which may overestimate the degree of freedom. We conclude that the comparative advantage (or disadvantage) of the genotype-based test over the allele-based test mainly depends on two parameters, the allele frequency difference delta and the Hardy-Weinberg disequilibrium coefficient difference delta_epsilon. Six different situations, called "phases", characterized by the two X^2 test statistics in allele-based and genotype-based test, are well separated in the phase diagram parameterized by delta and delta_epsilon. For two major groups of phases, a single parameter theta = tan^-1 (delta/delta_epsilon) is able to achieves an almost perfect phase separation. We also applied the analytic result to several types of disease models. It is shown that for dominant and additive models, genotype-based tests are favored over allele-based tests.

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arXiv2006

Utilizing of protein splicing phenomenon for optimization of obtaining and purification of the recombinant human growth hormone

Protein splicing is a post-translational autocatalystic excision of internal protein sequence (intein) with the subsequent ligation of the flanking polypeptides (exteins). The high specificity of excision ensured by intein makes it possible to use a phenomenon of protein splicing for the biotechnology purposes. The aim of this work was optimization of obtaining and purification of the recombinant human growth hormone using the protein splicing. It was experimentally demonstrated that the use of modified intein as auto-removal affine marker makes it possible to perform the rapid and cheap isolation of the recombinant protein Hgh. Furthermore, this approach allows to obtain the human growth hormone with native N-terminus, without formyl-metionine. Key words: intein, human growth hormone, protein splicing

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arXiv2007

Associative learning in biochemical networks

We develop a simple, chemostat-based model illustrating how a process analogous to associative learning can occur in a biochemical network. Associative learning is a form of learning whereby a system "learns" to associate two stimuli with one another. In our model, two types of replicating molecules, denoted A and B, are present in some initial concentration in the chemostat. Molecules A and B are stimulated to replicate by some growth factors, denoted GA and GB, respectively. It is also assumed that A and B can covalently link, and that the conjugated molecule can be stimulated by either the GA or GB growth factors (and can be degraded). We show that, if the chemostat is stimulated by both growth factors for a certain time, followed by a time gap during which the chemostat is not stimulated at all, and if the chemostat is then stimulated again by only one of the growth factors, then there will be a transient increase in the number of molecules activated by the other growth factor. Therefore, the chemostat bears the imprint of earlier, simultaneous stimulation with both growth factors, which is indicative of associative learning. It is interesting to note that the dynamics of our model is consistent with various aspects of Pavlov's original series of associative learning experiments in dogs. We discuss how associative learning can potentially be performed in vitro within RNA, DNA, or peptide networks. We also highlight how such a mechanism could potentially be involved in genomic evolution, and suggest bioinformatics studies that could be used to find evidence for associative learning processes at work inside living cells.

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arXiv2007

An HIV Feedback-Resistor: Auto-Regulatory Circuit Deactivator and Noise Buffer

Many viruses have the cunning ability to enter a hibernative or off state, termed latency or lysogeny. When in a latent state, the virus is unable to replicate, and its gene expression program is largely shut down. This facility for lying dormant typically ensures lifelong persistence of the virus in the host; it is also a particularly problematic obstacle in the treatment of HIV. For most viruses, the molecular regulation of entry into latency is not completely understood, but it is believed that viral gene expression must be deactivated in some way. In this study, we introduce a new regulatory motif, the feedback resistor, that enables a genetic circuit to shut off without the need for an active repressor molecule. We first show that many animal viruses might encode feedback resistors in their regulatory circuits. Then, by using a combination of mathematical theory and single-cell real-time imaging experiments, we show that a feedback resistor in the HIV Tat transcriptional circuit likely allows the HIV virus to enter into latency. We postulate that feedback resistors may give increased stability and control in the complex noisy signaling environment of the cell.

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arXiv2007

Effective Potential Energy Expression for Membrane Transport

All living cells transport molecules and ions across membranes, often against concentration gradients. This active transport requires continual energy expenditure and is clearly a nonequilibrium process for which standard equilibrium thermodynamics is not rigorously applicable. Here we derive a nonequilibrium effective potential that evaluates the per particle transport energy invested by the membrane. A novel method is used whereby a Hamiltonian function is constructed using particle concentrations as generalized coordinates. The associated generalized momenta are simply related to the individual particle energy from which we identify the effective potential. Examples are given and the formalism is compared with the equilibrium Gibb's free energy.

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arXiv2007

The Role of Lipid Bilayer Mechanics in Mechanosensation

Mechanosensation is a key part of the sensory repertoire of a vast array of different cells and organisms. The molecular dissection of the origins of mechanosensation is rapidly advancing as a result of both structural and functional studies. One intriguing mode of mechanosensation results from tension in the membrane of the cell (or vesicle) of interest. The aim of this review is to catalogue recent work that uses a mix of continuum and statistical mechanics to explore the role of the lipid bilayer in the function of mechanosensitive channels that respond to membrane tension. The role of bilayer deformation will be explored in the context of the well known mechanosensitive channel MscL. Additionally, we make suggestions for bridging gaps between our current theoretical understanding and common experimental techniques.

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arXiv2007

The microtubule transistor

I point out the similarity between the microtubule experiment reported by Priel et al [Biophys. J. 90, 4639 (2006)] and the ZnO nanowire experiment of Wang et al [Nanolett. 6, 2768 (2006)]. It is quite possible that MTs are similar to a piezoelectric field effect transistor for which the role of the control gate electrode is played by the piezo-induced electric field across the width of the MT walls and their elastic bending features

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arXiv2012

The macroscopic effects of microscopic heterogeneity

Over the past decade, advances in super-resolution microscopy and particle-based modeling have driven an intense interest in investigating spatial heterogeneity at the level of single molecules in cells. Remarkably, it is becoming clear that spatiotemporal correlations between just a few molecules can have profound effects on the signaling behavior of the entire cell. While such correlations are often explicitly imposed by molecular structures such as rafts, clusters, or scaffolds, they also arise intrinsically, due strictly to the small numbers of molecules involved, the finite speed of diffusion, and the effects of macromolecular crowding. In this chapter we review examples of both explicitly imposed and intrinsic correlations, focusing on the mechanisms by which microscopic heterogeneity is amplified to macroscopic effect.

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arXiv2016

Membrane tubulation by elongated and patchy nanoparticles

Advances in nanotechnology lead to an increasing interest in how nanoparticles interact with biomembranes. Nanoparticles are wrapped spontaneously by biomembranes if the adhesive interactions between the particles and membranes compensate for the cost of membrane bending. In the last years, the cooperative wrapping of spherical nanoparticles in membrane tubules has been observed in experiments and simulations. For spherical nanoparticles, the stability of the particle-filled membrane tubules strongly depends on the range of the adhesive particle-membrane interactions. In this article, we show via modeling and energy minimization that elongated and patchy particles are wrapped cooperatively in membrane tubules that are highly stable for all ranges of the particle-membrane interactions, compared to individual wrapping of the particles. The cooperative wrapping of linear chains of elongated or patchy particles in membrane tubules may thus provide an efficient route to induce membrane tubulation, or to store such particles in membranes.

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