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Mechanical state, material properties and continuous description of an epithelial tissue

During development, epithelial tissues undergo extensive morphogenesis based on coordinated changes of cell shape and position over time. Continuum mechanics describes tissue mechanical state and shape changes in terms of strain and stress. It accounts for individual cell properties using only a few spatially averaged material parameters. To determine the mechanical state and parameters in the Drosophila pupa dorsal thorax epithelium, we sever in vivo the adherens junctions around a disk-shaped domain comprising typically hundred cells. This enables a direct measurement of the strain along different orientations at once. The amplitude and anisotropy of the strain increase during development. We also measure the stress to viscosity ratio and similarly find an increase in amplitude and anisotropy. The relaxation time is of order of ten seconds. We propose a space-time, continuous model of the relaxation. Good agreement with experimental data validates the description of the epithelial domain as a continuous, linear, visco-elastic material. We discuss the relevant time and length scales. Another material parameter, the ratio of external friction to internal viscosity, is estimated by fitting the initial velocity profile. Together, our results contribute to quantify forces and displacements, and their time evolution during morphogenesis.

q-bio.CB↗

Developing a computational model of blood platelets with fluid dynamics applications

This paper worked towards modeling blood platelets. Blood platelets, also known as thrombocytes, play a key role in blood clotting which is a vital human function. Furthermore, the role of these entities in strokes, myocardial infarctions, and coronary artery disease add to the importance of blood platelets. Analytical expressions for the structure of blood platelets in both their inactivated and activated states were developed, beginning with randomized two-dimensional models in polar coordinates. Weak frameworks in spherical and cylindrical systems were then created. Next, using rotational matrices to change the position and direction of a simple projection, useful, explicit, parametric system of equations were attained in three-dimensional Cartesian space which roughly approximate the structure of a blood platelet. Finally, a methodology to return the drag coefficient ($c_d$) for any inputted set of blood platelet images was designed. This method was incorporated into a C++ program returning the functional representation and drag coefficient of any given platelet. This work has primary applications in computational biophysics and fluid dynamics. Additionally, if the parameters of the model are extended, there could be ramifications in other areas of scientific modelling by connecting analytical expressions with instrinsic characteristics.

q-bio.CB↗

Cytokine expression in malaria-infected non-human primate placentas

Malaria parasites are known to mediate the induction of inflammatory immune responses at the maternal-foetal interface during placental malaria (PM) leading to adverse consequences like pre-term deliveries and abortions. Immunological events that take place within the malaria-infected placental micro-environment leading to retarded foetal growth and disruption of pregnancies are among the critical parameters that are still in need of further elucidation. The establishment of more animal models for studying placental malaria can provide novel ways of circumventing problems experienced during placental malaria research in humans such as inaccurate estimation of gestational ages. Using the newly established olive baboon (Papio anubis)-Plasmodium knowlesi (P. knowlesi) H strain model of placental malaria, experiments were carried out to determine placental cytokine profiles underlying the immunopathogenesis of placental malaria. Four pregnant olive baboons were infected with blood stage P. knowlesi H strain parasites on the one fiftieth day of gestation while four other uninfected pregnant olive baboons were maintained as uninfected controls. After nine days of infection, placentas were extracted from all the eight baboons through cesarean surgery and used for the processing of placental plasma and sera samples for cytokine sandwich enzyme linked immunosorbent assays (ELISA). Results indicated that the occurrence of placental malaria was associated with elevated concentrations of tumour necrosis factor alpha (TNF-α) and interleukin 12 (IL-12). Increased levels of IL-4, IL-6 and IL-10 and interferon gamma (IFN-γ) levels were detected in uninfected placentas. These findings match previous reports regarding immunity during PM thereby demonstrating the reliability of the olive baboon-P. knowlesi model for use in further studies.

q-bio.CB↗

Effect of intracellular diffusion on current-voltage curves in potassium channels

We study the effect of intracellular ion diffusion on ionic currents permeating through the cell membrane. Ion flux across the cell membrane is mediated by special proteins forming specific channels. The structure of potassium channels have been widely studied in recent years with remarkable results: very precise measurements of the true current across a single channel are now available. Nevertheless, a complete understanding of the behavior of the channel is still lacking, though molecular dynamics and kinetic models have provided partial insights. In this paper we demonstrate, by analyzing the KcsA current-voltage currents via a suitable lattice model, that intracellular diffusion plays a crucial role in the permeation phenomenon. The interplay between the selectivity filter behavior and the ion diffusion in the intracellular side allows a full explanation of the current-voltage curves.

q-bio.CB↗

Finding the Ion Current Density of Microtubules by defining a potential function for the same and Solving the time independent Schrodinger Equation

In this paper, we model a microtubule based on its dimer resolution structure. First, the fundamental structural components were studied and then electrostatic potential function for a single monomer was calculated. Subsequently, the potential function inside a single monomer due to a ring of dimers was obtained. Considering the potential due to protofilament-protofilament interaction with a monomer in a B crystal structure of a microtubule, we obtain a double well potential wall. Quantum mechanically the ions can pass through this wall because of the Tunnelling effect. We solve the time independent Schrodinger Equation, calculate the transmission efficiency of ion flow and use the latter in the calculation of ion current density.

q-bio.CB↗

Chemical sensing by cell-surface chemoreceptor arrays: the roles of receptor cooperativity and adaptation

Most sensory cells use cross-membrane chemoreceptors to detect chemical signals in the environment. The biochemical properties and spatial organization of chemoreceptors play important roles in achieving and maintaining sensitivity and accuracy of chemical sensing. Here we investigate the effects of receptor cooperativity and adaptation on the limits of gradient sensing. We study a single cell with aggregated chemoreceptor arrays on the cell surface and derive general formula to the limits for gradient sensing from the uncertainty of instantaneous receptor activity. In comparison to independent receptors, we find that cooperativity by non-adaptative receptors could significantly lower the sensing limit in a chemical concentration range determined by the biochemical properties of ligand-receptor binding and ligand-induced receptor activity. Cooperativity by adaptative receptors are beneficial to gradient sensing within a broad range of background concentrations. Our results also show that isotropic receptor aggregate layout on the cell surface represents an optimal configuration to gradient sensing.

q-bio.CB↗

Screening of antibacterial activity of lactic acid bacteria isolated from fermented vegetables against food borne pathogens

This study aims to screen the antibacterial activity of lactic acid bacteria (LAB) isolated from home-made fermented vegetables against common food borne pathogens. The antagonistic properties of these isolates against Escherichia coli, Staphylococcus aureus, Yersinia enterocolitica and Bacillus cereus were examined using agar well diffusion method. Four LAB namely MF6, MF10, MF13, and MF15 identified as Lactobacillus animalis, Lactobacillus rhamnosus, Lactobacillus fermentum and Lactobacillus reuteri, respectively were effective against all selected pathogenic strains. Amongst the four isolates, MF6 exhibited the highest antibacterial activity, against all the indicator pathogens tested except Y. enterocolitic. Its activity was maximum against E.coli with a Zone of Inhibition (ZOI) ranging from 18.7 to 21.3 mm and least for Y. enterocolitica (10 \pm 1.1 mm). Isolate MF13 also showed antimicrobial property against all tested pathogens showing highest activity against Y. enterocolitica (14 \pm 1.7 mm) and least against E.coli (8 \pm 1.4 mm), which was in direct contrast to isolate MF6. Isolate MF15 showed greater activity against E.coli (12 \pm 0.8 mm) and least against S. aureus (8 \pm 1.7 mm). Least antimicrobial property was observed in isolate MF10, with a ZOI in the range of 2.5-7 mm. The degree of antimicrobial property among the isolates was in the order of MF6>MF13>MF15>MF10. Overall, the isolated LAB showed the remarkable inhibitory effect against both Gram positive and Gram negative pathogenic strains. However, the spectrum of inhibition was different for the isolates tested. These results suggest that this potent isolates could be used as a natural biopreservatives in different food products.

q-bio.CB↗

Model of cell response to α-particle radiation

Starting from a general equation for organism (or cell system) growth and attributing additional cell death rate (besides the natural rate) to therapy, we derive an equation for cell response to α radiation. Different from previous models that are based on statistical theory, the present model connects the consequence of radiation with the growth process of a biosystem and each variable or parameter has meaning regarding the cell evolving process. We apply this equation to model the dose response for α-particle radiation. It interprets the results of both high and low linear energy transfer (LET) radiations. When LET is high, the additional death rate is a constant, which implies that the localized cells are damaged immediately and the additional death rate is proportional to the number of cells present. While at low LET, the additional death rate includes a constant term and a linear term of radiation dose, implying that the damage to some cell nuclei has a time accumulating effect. This model indicates that the oxygen-enhancement ratio (OER) decreases while LET increases consistently.

physics.med-ph↗

Quality Control System Response to Stochastic Growth of Amyloid Fibrils

We introduce a stochastic model describing aggregation of misfolded proteins and degradation by the protein quality control system in a single cell. In analogy with existing literature, aggregates can grow, nucleate and fragment stochastically. We assume that the quality control system acts as an enzyme that can degrade aggregates at different stages of the growth process, with an efficiency that decreases with the size of the aggregate. We show how this stochastic dynamics, depending on the parameter choice, leads to two qualitatively different behaviors: a homeostatic state, where the quality control system is stable and aggregates of large sizes are not formed, and an oscillatory state, where the quality control system periodically breaks down, allowing for the formation of large aggregates. We discuss how these periodic breakdowns may constitute a mechanism for the sporadic development of neurodegenerative diseases.

q-bio.CB↗

Modelling proportionate growth

An important question in biology is how the relative size of different organs is kept nearly constant during growth of an animal. This property, called proportionate growth, has received increased attention in recent years. We discuss our recent work on a simple model where this feature comes out quite naturally from local rules, without fine tuning any parameter. The patterns produced are composed of large distinguishable structures with sharp boundaries, all of which grow at the same rate, keeping their overall shapes unchanged.

cond-mat.stat-mech↗

Tracking Tetrahymena Pyriformis Cells using Decision Trees

Matching cells over time has long been the most difficult step in cell tracking. In this paper, we approach this problem by recasting it as a classification problem. We construct a feature set for each cell, and compute a feature difference vector between a cell in the current frame and a cell in a previous frame. Then we determine whether the two cells represent the same cell over time by training decision trees as our binary classifiers. With the output of decision trees, we are able to formulate an assignment problem for our cell association task and solve it using a modified version of the Hungarian algorithm.

cs.CV↗

Unified approach to growth and aging in biological, technical and biotechnical systems

Complex systems, in many different scientific sectors, show coarse-grain properties with simple growth laws with respect to fundamental microscopic algorithms. We propose a classification scheme of growth laws which includes human aging, tumor (and/or tissue) growth, logistic and generalized logistic growth and the aging of technical devices. The proposed classification permits to evaluate the aging/failure of combined new bio-technical "manufactured products", where part of the system evolves in time according to biological-mortality laws and part according to technical device behaviors. Moreover it suggests a direct relation between the mortality leveling-off for humans and technical devices and the observed small cure probability for large tumors.

physics.bio-ph↗

The Medusa of Spatial Sorting: Topological Construction

We consider the simultaneous movement of finitely many colored points in space, calling it a spatial sorting process. The name suggests a purpose that drives the collection to a configuration of increased or decreased order. Mapping such a process to a subset of space-time, we use persistent homology measurements of the time function to characterize the process topologically.

cs.CG↗

A New Approach to Understanding Ontogenesis and The Theory of Aging

This paper proposes an original theory of aging of multicellular organisms. The cells of multicellular organisms, in contrast to unicellular organisms, are burdened with a two- part genome: housekeeping and specialized (multicellular), responsible for ontogenesis and terminal differentiation. The two parts of the genome compete for limited adaptive resources thereby interfering with the ability of the house-keeping part of the genome to adequately perform reparative and adaptive functions in post mitotic cells. The necessity to complete the ontgenesis program, leads to increased activity of the multicellular components of the genome. As a result, the allocation of cellular resources to specialized genome con-tinuously increases with time. This leads to a deficit of reparative and adaptive capacity in post mitotic cells. Suggestions for future research focus on identifying groups of genes responsible for regulation of growth rate of specialized genome and suppressing ability of the cell division. A better understanding of the relationship between the two parts of the genome will not only help us to manipulate ontogenesis and aging, but will also improve our understanding of cancer development and ontogenesis.

q-bio.CB↗

Achieving Control of Lesion Growth in CNS with Minimal Damage

Lesions in central nervous system (CNS) and their growth leads to debilitating diseases like Multiple Sclerosis (MS), Alzheimer's etc. We developed a model earlier which shows how the lesion growth can be arrested through a beneficial auto-immune mechanism. The success of the approach depends on a set of control parameters and their phase space was shown to have a smooth manifold separating the uncontrolled lesion growth region from the controlled. Here we show that an optimal set of parameter values exist which minimizes system damage while achieving control of lesion growth.

nlin.AO↗

Quorum sensing contributes to activated B cell homeostasis and to prevent autoimmunity

Maintenance of plasma IgM levels is critical for immune system function and homeostasis in humans and mice. However, the mechanisms that control homeostasis of the activated IgM-secreting B cells are unknown. After adoptive transfer into immune-deficient hosts, B-lymphocytes expand poorly but fully reconstitute the pool of natural IgM-secreting cells and circulating IgM levels. By using sequential cell transfers and B cell populations from several mutant mice, we were able to identify novel mechanisms regulating the size of the IgM-secreting B cell pool. Contrary to previous mechanisms described regulating homeostasis, which involve competition for the same niche by cells having overlapping survival requirements, homeostasis of the innate IgM-secreting B cell pool is also achieved when B cells populations are able to monitor the number of activated B cells by detecting their secreted products. Notably, B cell populations are able to assess the density of activated B cells by sensing their secreted IgG. This process involves the FcγRIIB, a low-affinity IgG receptor that is expressed on B cells and acts as a negative regulator of B cell activation, and its intracellular effector the inositol phosphatase SHIP. As a result of the engagement of this inhibitory pathway the number of activated IgM-secreting B cells is kept under control. We hypothesize that malfunction of this quorum-sensing mechanism may lead to uncontrolled B cell activation and autoimmunity.

q-bio.CB↗

Non-homogeneous random walks, subdiffusive migration of cells and anomalous chemotaxis

This paper is concerned with a non-homogeneous in space and non-local in time random walk model for anomalous subdiffusive transport of cells. Starting with a Markov model involving a structured probability density function, we derive the non-local in time master equation and fractional equation for the probability of cell position. We show the structural instability of fractional subdiffusive equation with respect to the partial variations of anomalous exponent. We find the criteria under which the anomalous aggregation of cells takes place in the semi-infinite domain.

cond-mat.stat-mech↗

Tessellations and Pattern Formation in Plant Growth and Development

The shoot apical meristem (SAM) is a dome-shaped collection of cells at the apex of growing plants from which all above-ground tissue ultimately derives. In Arabidopsis thaliana (thale cress), a small flowering weed of the Brassicaceae family (related to mustard and cabbage), the SAM typically contains some three to five hundred cells that range from five to ten microns in diameter. These cells are organized into several distinct zones that maintain their topological and functional relationships throughout the life of the plant. As the plant grows, organs (primordia) form on its surface flanks in a phyllotactic pattern that develop into new shoots, leaves, and flowers. Cross-sections through the meristem reveal a pattern of polygonal tessellation that is suggestive of Voronoi diagrams derived from the centroids of cellular nuclei. In this chapter we explore some of the properties of these patterns within the meristem and explore the applicability of simple, standard mathematical models of their geometry.

q-bio.CB↗