SEARCH · Searcharxiv

Results for “q-bio.CB”

Search indexed arXiv papers on artificial intelligence, large language models, computer vision and robotics. Read source abstracts and follow links to arXiv.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources

arXiv2013

A Comparison and Catalog of Intrinsic Tumor Growth Models

Determining the mathematical dynamics and associated parameter values that should be used to accurately reflect tumor growth continues to be of interest to mathematical modelers, experimentalists and practitioners. However, while there are several competing canonical tumor growth models that are often implemented, how to determine which of the models should be used for which tumor types remains an open question. In this work, we determine the best fit growth dynamics and associated parameter ranges for ten different tumor types by fitting growth functions to at least five sets of published experimental growth data per type of tumor. These time-series tumor growth data are used to determine which of the five most common tumor growth models (exponential, power law, logistic, Gompertz, or von Bertalanffy) provides the best fit for each type of tumor.

q-bio.CB↗

arXiv2013

Optimal shapes and stresses of adherent cells on patterned substrates

We investigate a continuum mechanical model for an adherent cell on two dimensional adhesive micropatterned substrates. The cell is modeled as an isotropic and homogeneous elastic material subject to uniform internal contractile stresses. The build-up of tension from cortical actin bundles at the cell periphery is incorporated by introducing an energy cost for bending of the cell boundary, resulting to a resistance to changes in local curvature. Integrin-based adhesions are modeled as harmonic springs, that pin the cell to adhesive patches of a predefined geometry. Using Monte Carlo simulations and analytical techniques we investigate the competing effects of bulk contractility and cortical bending rigidity in regulating cell shapes on non-adherent regions. We show that the crossover from convex to concave cell edges is controlled by the interplay between contractile stresses and boundary bending rigidity. In particular, the cell boundary becomes concave beyond a critical value of the contractile stress that is proportional to the cortical bending rigidity. Furthermore, the intracellular stresses are found largely concentrated at the concave edge of the cell. The model can be used to generate a cell-shape phase diagram for each specific adhesion geometry.

physics.bio-ph↗

arXiv2014

Global Hopf Bifurcation in the ZIP regulatory system

Regulation of zinc uptake in roots of Arabidopsis thaliana has recently been modeled by a system of ordinary differential equations based on the uptake of zinc, expression of a transporter protein and the interaction between an activator and inhibitor. For certain parameter choices the steady state of this model becomes unstable upon variation in the external zinc concentration. Numerical results show periodic orbits emerging between two critical values of the external zinc concentration. Here we show the existence of a global Hopf bifurcation with a continuous family of stable periodic orbits between two Hopf bifurcation points. The stability of the orbits in a neighborhood of the bifurcation points is analyzed by deriving the normal form, while the stability of the orbits in the global continuation is shown by calculation of the Floquet multipliers. From a biological point of view, stable periodic orbits lead to potentially toxic zinc peaks in plant cells. Buffering is believed to be an efficient way to deal with strong transient variations in zinc supply. We extend the model by a buffer reaction and analyze the stability of the steady state in dependence of the properties of this reaction. We find that a large enough equilibrium constant of the buffering reaction stabilizes the steady state and prevents the development of oscillations. Hence, our results suggest that buffering has a key role in the dynamics of zinc homeostasis in plant cells.

math.DS↗

arXiv2014

On the conflict between precision and robustness in the proportion regulation of cell types

In Dictyostelium discoideum the proportion of cell types is known to be actively regulated, recovering, for example, after the removal of a given cell type. However, we have recently shown that regulation is intrinsically imprecise: it controls the proportion above/below certain upper and lower thresholds, but not within an allowed range of values that these thresholds define. To explain this finding we present a model based on (i) a global negative feedback, and (ii) a cell-autonomous positive feedback leading to a hysteresis-like behaviour (i.e, a bistability of cell type). The simulated cell-type proportion is indeed found to span a range of values as a consequence of the bistability. We conclude that there is a general conflict between the precision of proportion regulation and the robustness of the differentiation of cell types.

physics.bio-ph↗

arXiv2014

The role of mechanical forces in the planar-to-bulk transition in growing Escherichia coli microcolonies

Mechanical forces are obviously important in the assembly of three-dimensional multicellular structures, but their detailed role is often unclear. We have used growing microcolonies of the bacterium \emph{Escherichia coli} to investigate the role of mechanical forces in the transition from two-dimensional growth (on the interface between a hard surface and a soft agarose pad) to three-dimensional growth (invasion of the agarose). We measure the position within the colony where the invasion transition happens, the cell density within the colony, and the colony size at the transition as functions of the concentration of the agarose. We use a phenomenological theory, combined with individual-based computer simulations, to show how mechanical forces acting between the bacterial cells, and between the bacteria and the surrounding matrix, lead to the complex phenomena observed in our experiments - in particular a non-trivial dependence of the colony size at the transition on the agarose concentration. Matching these approaches leads to a prediction for how the friction coefficient between the bacteria and the agarose should vary with agarose concentration. Our experimental conditions mimic numerous clinical and environmental scenarios in which bacteria invade soft matrices, as well as shedding more general light on the transition between two- and three-dimensional growth in multicellular assemblies.

q-bio.CB↗

arXiv2014

Spontaneous oscillations from turnover of an elastic contractile material

Single and collective cellular oscillations involving the actomyosin cytoskeleton have been observed in numerous biological systems. We show here that a generic model of a contractile material, which is turning over and contracts against an elastic element, exhibits spontaneous oscillations. Such a model can thus account for shape oscillations observed in amnioserosa cells during dorsal closure of the Drosophila embryo. We investigate the collective dynamics of an ensemble of such oscillators and show that the relative contribution of viscous and friction losses yield different regimes of collective oscillations. Taking into account the diffusion of contractile elements, our theoretical framework predicts the appearance of traveling waves which might account for the propagation of actomyosin contractile waves observed during morphogenesis.

physics.bio-ph↗

arXiv2014

Collective motion of cells: from experiments to models

Swarming or collective motion of living entities is one of the most common and spectacular manifestations of living systems having been extensively studied in recent years. A number of general principles have been established. The interactions at the level of cells are quite different from those among individual animals therefore the study of collective motion of cells is likely to reveal some specific important features which are overviewed in this paper. In addition to presenting the most appealing results from the quickly growing related literature we also deliver a critical discussion of the emerging picture and summarize our present understanding of collective motion at the cellular level. Collective motion of cells plays an essential role in a number of experimental and real-life situations. In most cases the coordinated motion is a helpful aspect of the given phenomenon and results in making a related process more efficient (e.g., embryogenesis or wound healing), while in the case of tumor cell invasion it appears to speed up the progression of the disease. In these mechanisms cells both have to be motile and adhere to one another, the adherence feature being the most specific to this sort of collective behavior. One of the central aims of this review is both presenting the related experimental observations and treating them in the light of a few basic computational models so as to make an interpretation of the phenomena at a quantitative level as well.

q-bio.CB↗

arXiv2014

MHC Restriction of V-V Interactions in Serum IgG

According to Jerne's idiotypic network hypothesis, the adaptive immune system is regulated by interactions between the variable regions of antibodies, B cells, and T cells.1 The symmetrical immune network theory2,3 is based on Jerne's hypothesis, and provides a basis for understanding many of the phenomena of adaptive immunity. The theory includes the postulate that the repertoire of serum IgG molecules is regulated by T cells, with the result that IgG molecules express V region determinants that mimic V region determinants present on suppressor T cells. In this paper we describe rapid binding between purified murine serum IgG of H-2b and H-2d mice and serum IgG from the same strain and from MHC-matched mice, but not between serum IgG preparations of mice with different MHC genes. We interpret this surprising finding in terms of a model in which IgG molecules are selected to have both anti-anti-(self MHC class II) and anti-anti-anti-(self MHC class II) specificity.

q-bio.CB↗

arXiv2014

Flagellar Synchronization Through Direct Hydrodynamic Interactions

Microscale fluid flows generated by ensembles of beating eukaryotic flagella are crucial to fundamental processes such as development, motility and sensing. Despite significant experimental and theoretical progress, the underlying physical mechanisms behind this striking coordination remain unclear. Here, we present a novel series of experiments in which the flagellar dynamics of two micropipette-held somatic cells of Volvox carteri, with measurably different intrinsic beating frequencies, are studied by high-speed imaging as a function of their mutual separation and orientation. From analysis of beating time series we find that the interflagellar coupling, which is constrained by the lack of chemical and mechanical connections between the cells to be purely hydrodynamical, exhibits a spatial dependence that is consistent with theoretical predictions. At close spacings it produces robust synchrony which can prevail for thousands of flagellar beats, while at increasing separations this synchrony is systematically degraded by stochastic processes. Manipulation of the relative flagellar orientation reveals the existence of both in-phase and antiphase synchronized states, which is consistent with dynamical theories. Through dynamic flagellar tracking with exquisite spatio-temporal precision, we quantify changes in beating waveforms that result from altered coupling configuration and distance of separation. The experimental results of this study prove unequivocally that flagella coupled solely through a fluid medium can achieve robust synchrony despite significant differences in their intrinsic properties.

cond-mat.soft↗

arXiv2014

Stochastic noise reduction upon complexification: positively correlated birth-death type systems

Cell systems consist of a huge number of various molecules that display specific patterns of interactions, which have a determining influence on the cell's functioning. In general, such complexity is seen to increase with the complexity of the organism, with a concomitant increase of the accuracy and specificity of the cellular processes. The question thus arises how the complexification of systems - modeled here by simple interacting birth-death type processes - can lead to a reduction of the noise - described by the variance of the number of molecules. To gain understanding of this issue, we investigated the difference between a single system containing molecules that are produced and degraded, and the same system - with the same average number of molecules - connected to a buffer. We modeled these systems using Ito stochastic differential equations in discrete time, as they allow straightforward analytical developments. In general, when the molecules in the system and the buffer are positively correlated, the variance on the number of molecules in the system is found to decrease compared to the equivalent system without a buffer. Only buffers that are too noisy by themselves tend to increase the noise in the main system. We tested this result on two model cases, in which the system and the buffer contain proteins in their active and inactive state, or protein monomers and homodimers. We found that in the second test case, where the interconversion terms are non-linear in the number of molecules, the noise reduction is much more pronounced; it reaches up to 20% reduction of the Fano factor with the parameter values tested in numerical simulations on an unperturbed birth-death model. We extended our analysis to two arbitrary interconnected systems.

q-bio.BM↗

arXiv2014

Contractile and mechanical properties in epithelia with perturbed actomyosin dynamics

Mechanics has an important role during morphogenesis, both in the generation of forces driving cell shape changes and in determining the effective material properties of cells and tissues. Drosophila dorsal closure (DC) has emerged as a model system for studying the interplay between tissue mechanics and cellular activity. Thereby, the amnioserosa (AS) generates one of the major forces that drive DC through the apical contraction of its constituent cells. We combined quantitation of live data, genetic and mechanical perturbation and cell biology, to investigate how mechanical properties and contraction rate emerge from cytoskeletal activity. We found that a decrease in Myosin phosphorylation induces a fluidization of AS cells which become more compliant. Conversely, an increase in Myosin phosphorylation and an increase in actin linear polymerization induce a solidification of cells. Contrary to expectation, these two perturbations have an opposite effect on the strain rate of cells during DC. While an increase in actin polymerization increases the contraction rate of AS cells, an increase in Myosin phosphorylation gives rise to cells that contract very slowly. The quantification of how the perturbation induced by laser ablation decays throughout the tissue revealed that the tissue in these two mutant backgrounds reacts very differently. We suggest that the differences in the strain rate of cells in situations where Myosin activity or actin polymerization is increased arise from changes in how the contractile forces are transmitted and coordinated across the tissue through ECadherin mediated adhesion. Our results show that there is an optimal level of Myosin activity to generate efficient contraction and suggest that the architecture of the actin cytoskeleton and the dynamics of adhesion complexes are important parameters for the emergence of coordinated activity throughout the tissue.

q-bio.CB↗

arXiv2015

Recognizing Cancer via Somatic and Organic Evolution

The fitness of somatic cells of metazoan, the ability of proliferation and survival, depends on microenvironment. In somatic evolution, a mutated cell in a tissue clonally expands abnormally because of its high fitness as normal cells in a corresponding microenvironment. In this study, we propose the cancer cell hypothesis that cancer cells are the mutated cells with two characteristics: clonal expansion and damaging the microenvironment through the behaviours such as producing more poison in metabolism than normal cells. This model provides an explanation for the nature of invasion and metastasis, which are still controversial. In addition, we theoretically reasoned out that normal cells have almost the highest fitness in healthy microenvironments as a result of long-term organic evolution. This inspires a new kind of therapy of cancer, which improving microenvironment to make cancer cells lower in fitness than normal cells and then halt the growth of tumours. This general therapy relies on a mechanism differing from chemotherapy and targeted therapy.

q-bio.PE↗

arXiv2014

Biocompatibility of Pristine Graphene Monolayers, Nanosheets and Thin Films

There is an increasing interest to develop nanoscale biocompatible graphene structures due to their desirable physicochemical properties, unlimited application opportunities and scalable production. Here we report the preparation, characterization and biocompatibility assessment of novel graphene flakes and their enabled thin films suitable for a wide range of biomedical and electronic applications. Graphene flakes were synthesized by a chemical vapour deposition method or a liquid-phase exfoliation procedure and then thin films were prepared by transferring graphene onto glass coverslips. Raman spectroscopy and transmission electron microscopy confirmed a predominantly monolayer and a high crystalline quality formation of graphene. The biocompatibility assessment of graphene thin films and graphene flakes was performed using cultured human lung epithelial cell line A549 employing a multimodal approach incorporating automated imaging, high content screening, real-time impedance sensing in combination with biochemical assays. No detectable changes in the cellular morphology or attachment of A549 cells growing on graphene thin films or cells exposed to graphene flakes (0.1 to 5 ug/mL) for 4 to 72 h was observed. Graphene treatments caused a very low level of increase in cellular production of reactive oxygen species in A549 cells, but no detectable damage to the nuclei such as changes in morphology, condensation or fragmentation was observed. In contrast, carbon black proved to be significantly more toxic than the graphene. These data open up a promising view of using graphene enabled composites for a diverse scope of safer applications.

q-bio.CB↗

arXiv2014

Spontaneous excitability in the Morris--Lecar model with ion channel noise

Noise induced excitability is studied in type I and II Morris-Lecar neurons subject to constant sub threshold input, where fluctuations arise from sodium and potassium ion channels. Ion channels open and close randomly, creating current fluctuations that can induce spontaneous firing of action potentials. Both noise sources are assumed to be weak so that spontaneous action potentials occur on a longer timescale than ion channel fluctuations. Asymptotic approximations of the stationary density function and most probable paths are developed to understand the role of channel noise in spontaneous excitability. Even though the deterministic dynamical behavior of type I and II action potentials differ, results show that a single mechanism explains how ion channel noise generates spontaneous action potentials.

q-bio.CB↗

arXiv2014

Extensive regulation of metabolism and growth during the cell division cycle

Yeast cells grown in culture can spontaneously synchronize their respiration, metabolism, gene expression and cell division. Such metabolic oscillations in synchronized cultures reflect single-cell oscillations, but the relationship between the oscillations in single cells and synchronized cultures is poorly understood. To understand this relationship and the coordination between metabolism and cell division, we collected and analyzed DNA-content, gene-expression and physiological data, at hundreds of time-points, from cultures metabolically-synchronized at different growth rates, carbon sources and biomass densities. The data enabled us to extend and generalize an ensemble-average-over-phases (EAP) model that connects the population-average gene-expression of asynchronous cultures to the gene-expression dynamics in the single-cells comprising the cultures. The extended model explains the carbon-source specific growth-rate responses of hundreds of genes. Our data demonstrate that for a given growth rate, the frequency of metabolic cycling in synchronized cultures increases with the biomass density. This observation underscores the difference between metabolic cycling in synchronized cultures and in single cells and suggests entraining of the single-cell cycle by a quorum-sensing mechanism. Constant levels of residual glucose during the metabolic cycling of synchronized cultures indicate that storage carbohydrates are required to fuel not only the G1/S transition of the division cycle but also the metabolic cycle. Despite the large variation in profiled conditions and in the time-scale of their dynamics, most genes preserve invariant dynamics of coordination with each other and with the rate of oxygen consumption. Similarly, the G1/S transition always occurs at the beginning, middle or end of the high oxygen consumption phases, analogous to observations in human and drosophila cells.

q-bio.GN↗

arXiv2014

From Intracellular Signaling to Population Oscillations: Bridging Scales in Collective Behavior

Collective behavior in cellular populations is coordinated by biochemical signaling networks within individual cells. Connecting the dynamics of these intracellular networks to the population phenomena they control poses a considerable challenge because of network complexity and our limited knowledge of kinetic parameters. However, from physical systems we know that behavioral changes in the individual constituents of a collectively-behaving system occur in a limited number of well-defined classes, and these can be described using simple models. Here we apply such an approach to the emergence of collective oscillations in cellular populations of the social amoeba Dictyostelium discoideum. Through direct tests of our model with quantitative in vivo measurements of single-cell and population signaling dynamics, we show how a simple model can effectively describe a complex molecular signaling network and its effects at multiple size and temporal scales. The model predicts novel noise-driven single-cell and population-level signaling phenomena that we then experimentally observe. Our results suggest that like physical systems, collective behavior in biology may be universal and described using simple mathematical models.

physics.bio-ph↗

arXiv2014

Efficacy of high frequency switched-mode stimulation in activating Purkinje cells

This paper investigates the efficacy of high frequency switched-mode neural stimulation. Instead of using a constant stimulation amplitude, the stimulus is switched on and off repeatedly with a high frequency (up to 100kHz) duty cycled signal. By means of tissue modeling that includes the dynamic properties of both the tissue material as well as the axon membrane, it is first shown that switched-mode stimulation depolarizes the cell membrane in a similar way as classical constant amplitude stimulation. These findings are subsequently verified using in vitro experiments in which the response of a Purkinje cell is measured due to a stimulation signal in the molecular layer of the cerebellum of a mouse. For this purpose a stimulator circuit is developed that is able to produce a monophasic high frequency switched-mode stimulation signal. The results confirm the modeling by showing that switched-mode stimulation is able to induce similar responses in the Purkinje cell as classical stimulation using a constant current source. This conclusion opens up possibilities for novel stimulation designs that can improve the performance of the stimulator circuitry. Care has to be taken to avoid losses in the system due to the higher operating frequency.

q-bio.NC↗

arXiv2014

The dynamics of sperm cooperation in a competitive environment

Sperm cooperation has evolved in a variety of taxa and is often considered a response to sperm competition, yet the benefit of this form of collective movement remains unclear. Here we use fine-scale imaging and a minimal mathematical model to study sperm aggregation in the rodent genus $Peromyscus$. We demonstrate that as the number of sperm cells in an aggregate increase, the group moves with more persistent linearity but without increasing speed; this benefit, however, is offset in larger aggregates as the geometry of the group forces sperm to swim against one another. The result is a non-monotonic relationship between aggregate size and average velocity with both a theoretically predicted and empirically observed optimum of 6-7 sperm/aggregate. To understand the role of sexual selection in driving these sperm group dynamics, we compared two sister-species with divergent mating systems and find that sperm of $P.\,maniculatus$ (highly promiscuous), which have evolved under intense competition, form optimal-sized aggregates more often than sperm of $P.\,polionotus$ (strictly monogamous), which lack competition. Our combined mathematical and experimental study of coordinated sperm movement reveals the importance of geometry, motion and group size on sperm velocity and suggests how these physical variables interact with evolutionary selective pressures to regulate cooperation in competitive environments.

q-bio.CB↗