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Physical Biology

Mikhail Tikhonov, William Bialek
The historical focus on network topology as a determinant of biological function is still largely maintained today, illustrated by the rise of structure-only approaches to network analysis. However, biochemical circuits and genetic regulatory networks are defined both by their topology and by a multitude of continuously adjustable parameters, such as the strength of interactions between nodes, also recognized as important. Here we present a class of simple perceptron-based Boolean models within which comparing the relative importance of topology versus interaction strengths becomes a quantitatively well-posed problem...
December 6, 2016: Physical Biology
Jacob Carroll, Matthew Raum, Kimberly Forsten-Williams, Uwe C Täuber
Surface plasmon resonance (SPR) chips are widely used to measure association and dissociation rates for the binding kinetics between two species of chemicals, e.g., cell receptors and ligands. It is commonly assumed that ligands are spatially well mixed in the SPR region, and hence a mean-field rate equation description is appropriate. This approximation however ignores the spatial fluctuations as well as temporal correlations induced by multiple local rebinding events, which become prominent for slow diffusion rates and high binding affinities...
December 6, 2016: Physical Biology
Paul François, Mathieu Hemery, Kyle A Johnson, Laura N Saunders
We consider the general problem of sensitive and specific discrimination between biochemical species. An important instance is immune discrimination between self and not-self, where it is also observed experimentally that ligands just below the discrimination threshold negatively impact response, a phenomenon called antagonism. We characterize mathematically the generic properties of such discrimination, first relating it to biochemical adaptation. Then, based on basic biochemical rules, we establish that, surprisingly, antagonism is a generic consequence of any strictly specific discrimination made independently from ligand concentration...
December 6, 2016: Physical Biology
Laura M McMillen, Dimitrios Vavylonis
Cell protrusion through polymerization of actin filaments at the leading edge of motile cells may be influenced by spatial gradients of diffuse actin and regulators. Here we study the distribution of two of the most important regulators, capping protein and Arp2/3 complex, which regulate actin polymerization in the lamellipodium through capping and nucleation of free barbed ends. We modeled their kinetics using data from prior single molecule microscopy experiments on XTC cells. These experiments have provided evidence for a broad distribution of diffusion coefficients of both capping protein and Arp2/3 complex...
December 6, 2016: Physical Biology
R Hermsen
The spatial range of a species habitat is generally determined by the ability of the species to cope with biotic and abiotic variables that vary in space. Therefore, the species range is itself an evolvable property. Indeed, environmental gradients permit a mode of evolution in which range expansion and adaptation go hand in hand. This process can contribute to rapid evolution of drug resistant bacteria and viruses, because drug concentrations in humans and livestock treated with antibiotics are far from uniform...
November 30, 2016: Physical Biology
Alan Veliz-Cuba, Chinmaya Gupta, Matthew R Bennett, Krešimir Josić, William Ott
We assess the impact of cell cycle noise on gene circuit dynamics. For bistable genetic switches and excitable circuits, we find that transitions between metastable states most likely occur just after cell division and that this concentration effect intensifies in the presence of transcriptional delay. We explain this concentration effect with a three-states stochastic model. For genetic oscillators, we quantify the temporal correlations between daughter cells induced by cell division. Temporal correlations must be captured properly in order to accurately quantify noise sources within gene networks...
November 30, 2016: Physical Biology
Aleem Syed, Neha Arora, Thomas A Bunch, Emily A Smith
Cysteine residues (Cys) in the membrane proximal region are common post-translational modification (PTM) sites in transmembrane proteins. Herein, the effects of a highly conserved membrane proximal α-subunit Cys(1368) on the diffusion properties of αPS2CβPS integrins are reported. Sequence alignment shows that this cysteine is palmitoylated in human α3 and α6 integrin subunits. Replacing Cys(1368) in wild-type integrins with valine (Val(1368)) putatively blocks a PTM site and alters integrins' ligand binding and diffusion characteristics...
November 15, 2016: Physical Biology
Nicole Meyer-Vernet, Jean-Pierre Rospars
Self-locomotion is central to animal behaviour and survival. It is generally analysed by focusing on preferred speeds and gaits under particular biological and physical constraints. In the present paper we focus instead on the maximum speed and we study its order-of-magnitude scaling with body size, from bacteria to the largest terrestrial and aquatic organisms. Using data for about 460 species of various taxonomic groups, we find a maximum relative speed of the order of magnitude of ten body lengths per second over a 10(20)-fold mass range of running and swimming animals...
November 15, 2016: Physical Biology
Anne E Hafner, Heiko Rieger
Intracellular transport is vital for the proper functioning and survival of a cell. Cargo (proteins, vesicles, organelles, etc) is transferred from its place of creation to its target locations via molecular motor assisted transport along cytoskeletal filaments. The transport efficiency is strongly affected by the spatial organization of the cytoskeleton, which constitutes an inhomogeneous, complex network. In cells with a centrosome microtubules grow radially from the central microtubule organizing center towards the cell periphery whereas actin filaments form a dense meshwork, the actin cortex, underneath the cell membrane with a broad range of orientations...
November 15, 2016: Physical Biology
Behruz Bozorg, Pawel Krupinski, Henrik Jönsson
Morphogenesis in plants and animals involves large irreversible deformations. In plants, the response of the cell wall material to internal and external forces is determined by its mechanical properties. An appropriate model for plant tissue growth must include key features such as anisotropic and heterogeneous elasticity and cell dependent evaluation of mechanical variables such as turgor pressure, stress and strain. In addition, a growth model needs to cope with cell divisions as a necessary part of the growth process...
November 15, 2016: Physical Biology
Andrea Cavagna, Daniele Conti, Irene Giardina, Tomas S Grigera, Stefania Melillo, Massimiliano Viale
Information transfer is an essential factor in determining the robustness of biological systems with distributed control. The most direct way to study the mechanisms ruling information transfer is to experimentally observe the propagation across the system of a signal triggered by some perturbation. However, this method may be inefficient for experiments in the field, as the possibilities to perturb the system are limited and empirical observations must rely on natural events. An alternative approach is to use spatio-temporal correlations to probe the information transfer mechanism directly from the spontaneous fluctuations of the system, without the need to have an actual propagating signal on record...
November 15, 2016: Physical Biology
Neda Dadashvand, Christina M Othon
Lipid structures exhibit complex and highly dynamic lateral structure; and changes in lipid density and fluidity are believed to play an essential role in membrane targeting and function. The dynamic structure of liquids on the molecular scale can exhibit complex transient density fluctuations. Here the lateral heterogeneity of lipid dynamics is explored in free standing lipid monolayers. As the temperature is lowered the probes exhibit increasingly broad and heterogeneous rotational correlation. This increase in heterogeneity appears to exhibit a critical onset, similar to those observed for glass forming fluids...
November 15, 2016: Physical Biology
Toshiko Ichiye
Although considerable progress has been made in the molecular biophysics of proteins, it is still not possible to reliably design an enzyme for a given function. The current understanding of enzyme function is that both structure and flexibility are important. Much attention has been focused recently on protein folding and thus structure, spurred on by insights from the folding funnel concept. For experimental studies of protein folding, variations in temperature (T) and chemical composition (X) of the solution have been traditionally exploited, although more recent studies using variations in pressure (P) made possible through new instrumentation have led to a deeper understanding of the energy landscape of protein folding...
November 15, 2016: Physical Biology
Long Liang, Christopher Jones, Shaohua Chen, Bo Sun, Yang Jiao
Collagen networks play an important role in coordinating and regulating collective cellular dynamics via a number of signaling pathways. Here, we investigate the transmission of forces generated by contractile cells in 3D collagen-I networks. Specifically, the graph (bond-node) representations of collagen networks with collagen concentrations of 1, 2 and 4 mg ml(-1) are derived from confocal microscopy data and used to model the network microstructure. Cell contraction is modeled by applying correlated displacements at specific nodes of the network, representing the focal adhesion sites...
October 25, 2016: Physical Biology
Anna Starzyk, Michał Wojciechowski, Marek Cieplak
We perform molecular dynamics simulations for a simple coarse-grained model of a protein placed inside of a softly repulsive sphere of radius R. The protein is surrounded either by a number of same molecules or a number of spherical crowding particles that immitate other biomolecules such as the osmolytes. The two descriptions are shown to lead to distinct results when testing thermal stability as assessed by studying the unfolding times as a function of temperature. We consider three examples of proteins and show that crowding increases the thermal stability provided the inter-protein or protein-crowder interactions are repulsive...
October 25, 2016: Physical Biology
H Behar, N Brenner, G Ariel, Y Louzoun
Cooperative interactions between individuals in a population and their stability properties are central to population dynamics and evolution. We introduce a generic class of nonlinear dynamical systems describing such interactions between producers and non-producers of a rapidly equilibrating common resource extracted from a finite environment. In the deterministic mean field approximation, fast-growing non-producers drive the entire population to extinction. However, the presence of arbitrarily small perturbations destabilizes this fixed point into a stochastic attractor where both phenotypes can survive...
October 18, 2016: Physical Biology
Xiuhong Cai, Xiang Li, Hong Qi, Fang Wei, Jianyong Chen, Jianwei Shuai
The gating properties of the inositol 1, 4, 5-trisphosphate (IP3) receptor (IP3R) are determined by the binding and unbinding capability of Ca(2+) ions and IP3 messengers. With the patch clamp experiments, the stationary properties have been discussed for Xenopus oocyte type-1 IP3R (Oo-IP3R1), type-3 IP3R (Oo-IP3R3) and Spodoptera frugiperda IP3R (Sf-IP3R). In this paper, in order to provide insights about the relation between the observed gating characteristics and the gating parameters in different IP3Rs, we apply the immune algorithm to fit the parameters of a modified DeYoung-Keizer model...
October 17, 2016: Physical Biology
Adam J M Wollman, Helen Miller, Simon Foster, Mark C Leake
Staphylococcus aureus is an important pathogen, giving rise to antimicrobial resistance in cell strains such as Methicillin Resistant S. aureus (MRSA). Here we report an image analysis framework for automated detection and image segmentation of cells in S. aureus cell clusters, and explicit identification of their cell division planes. We use a new combination of several existing analytical tools of image analysis to detect cellular and subcellular morphological features relevant to cell division from millisecond time scale sampled images of live pathogens at a detection precision of single molecules...
October 17, 2016: Physical Biology
David J Jörg, Andrew C Oates, Frank Jülicher
Rhythmic and sequential segmentation of the embryonic body plan is a vital developmental patterning process in all vertebrate species. However, a theoretical framework capturing the emergence of dynamic patterns of gene expression from the interplay of cell oscillations with tissue elongation and shortening and with signaling gradients, is still missing. Here we show that a set of coupled genetic oscillators in an elongating tissue that is regulated by diffusing and advected signaling molecules can account for segmentation as a self-organized patterning process...
October 11, 2016: Physical Biology
Daniel Dziob, Tomasz Kołodziej, Justyna Nowak, Piotr Cyzio, Joanna Raczkowska, Jadwiga Laska, Zenon Rajfur
Cell migration is an important biological phenomenon which depends on a number of internal and external factors. One of such factors can be the mechanical properties of the environment which can have an impact on the cell's regulatory pathways through so-called mechanotransduction. Ultimately, these properties can also influence the process of cell migration. The goal of this work is to investigate how substrate stiffness (elasticity) changes basic migration parameters of migrating cells. Fish keratocytes migrating on polyacrylamide hydrogels have been used as a model of fast migrating cells...
October 11, 2016: Physical Biology
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