Cellular Packing Research Articles

CdrA Interactions within the Pseudomonas aeruginosa Biofilm Matrix Safeguard It from Proteolysis and Promote Cellular Packing.

Biofilms are robust multicellular aggregates of bacteria that are encased in an extracellular matrix. Different bacterial species have been shown to use a range of biopolymers to build their matrices. Pseudomonas aeruginosa is a model organism for the laboratory study of biofilms, and past work has suggested that exopolysaccharides are a required matrix component. However, we found that expression of the matrix protein CdrA, in the absence of biofilm exopolysaccharides, allowed biofilm formation through the production of a CdrA-rich proteinaceous matrix. This represents a novel function for CdrA. Similar observations have been made for other species such as Escherichia coli and Staphylococcus aureus, which can utilize protein-dominant biofilm matrices. However, we found that these CdrA-containing matrices were susceptible to both exogenous and self-produced proteases. We previously reported that CdrA directly binds the biofilm matrix exopolysaccharide Psl. Now we have found that when CdrA bound to Psl, it was protected from proteolysis. Together, these results support the idea of the importance of multibiomolecular components in matrix stability and led us to propose a model in which CdrA-CdrA interactions can enhance cell-cell packing in an aggregate that is resistant to physical shear, while Psl-CdrA interactions enhance aggregate integrity in the presence of self-produced and exogenous proteases.IMPORTANCEPseudomonas aeruginosa forms multicellular aggregates or biofilms using both exopolysaccharides and the CdrA matrix adhesin. We showed for the first time that P. aeruginosa can use CdrA to build biofilms that do not require known matrix exopolysaccharides. It is appreciated that biofilm growth is protective against environmental assaults. However, little is known about how the interactions between individual matrix components aid in this protection. We found that interactions between CdrA and the exopolysaccharide Psl fortify the matrix by preventing CdrA proteolysis. When both components-CdrA and Psl-are part of the matrix, robust aggregates form that are tightly packed and protease resistant. These findings provide insight into how biofilms persist in protease-rich host environments.

Geometry, packing, and evolutionary paths to increased multicellular size.

The evolutionary transition to multicellularity transformed life on earth, heralding the evolution of large, complex organisms. Recent experiments demonstrated that laboratory-evolved multicellular "snowflake yeast" readily overcome the physical barriers that limit cluster size by modifying cellular geometry [Jacobeen et al., Nat. Phys. 14, 286 (2018)10.1038/s41567-017-0002-y]. However, it is unclear why this route to large size is observed, rather than an evolved increase in intercellular bond strength. Here, we use a geometric model of the snowflake yeast growth form to examine the geometric efficiency of increasing size by modifying geometry and bond strength. We find that changing geometry is a far more efficient route to large size than evolving increased intercellular adhesion. In fact, increasing cellular aspect ratio is on average ∼13 times more effective than increasing bond strength at increasing the number of cells in a cluster. Modifying other geometric parameters, such as the geometric arrangement of mother and daughter cells, also had larger effects on cluster size than increasing bond strength. Simulations reveal that as cells reproduce, internal stress in the cluster increases rapidly; thus, increasing bond strength provides diminishing returns in cluster size. Conversely, as cells become more elongated, cellular packing density within the cluster decreases, which substantially decreases the rate of internal stress accumulation. This suggests that geometrically imposed physical constraints may have been a key early selective force guiding the emergence of multicellular complexity.

Packing of flexible 2D materials in vesicles

To understand the mechanics of cellular packing of two-dimensional (2D) materials, we perform systematic molecular dynamics simulations and theoretical analysis to investigate the packing of a flexible circular sheet in a spherical vesicle and the 2D packing problem of a strip in a cylindrical vesicle. Depending on the system dimensions and the bending rigidity ratio between the confined sheet and the vesicle membrane, a variety of packing morphologies are observed, including a conical shape, a shape of three-fold symmetry, a cylindrically curved shape, an axisymmetrically buckled shape, as well as the initial circular shape. A set of buckling analyses lead to phase diagrams of the packing morphologies of the encapsulated sheets. These results may have important implications on the mechanism of intracellular packing and toxicity of 2D materials.

Approximate Bayesian computation reveals the importance of repeated measurements for parameterising cell-based models of growing tissues

The growth and dynamics of epithelial tissues govern many morphogenetic processes in embryonic development. A recent quantitative transition in data acquisition, facilitated by advances in genetic and live-imaging techniques, is paving the way for new insights to these processes. Computational models can help us understand and interpret observations, and then make predictions for future experiments that can distinguish between hypothesised mechanisms. Increasingly, cell-based modelling approaches such as vertex models are being used to help understand the mechanics underlying epithelial morphogenesis. These models typically seek to reproduce qualitative phenomena, such as cell sorting or tissue buckling. However, it remains unclear to what extent quantitative data can be used to constrain these models so that they can then be used to make quantitative, experimentally testable predictions. To address this issue, we perform an in silico study to investigate whether vertex model parameters can be inferred from imaging data, and explore methods to quantify the uncertainty of such estimates. Our approach requires the use of summary statistics to estimate parameters. Here, we focus on summary statistics of cellular packing and of laser ablation experiments, as are commonly reported from imaging studies. We find that including data from repeated experiments is necessary to generate reliable parameter estimates that can facilitate quantitative model predictions.

Mechanics of cellular packing of nanorods with finite and non-uniform diameters.

To understand the mechanics of cellular/intracellular packing of one-dimensional nanomaterials, we performed theoretical analysis and molecular dynamics simulations to investigate how the morphology and mechanical behaviors of a lipid vesicle are regulated by encapsulated rigid nanorods of finite and non-uniform diameters, including a cylindrical rod, a rod with widened ends, a cone-shaped rod, and a screwdriver-shaped rod. As the rod length increases, the vesicle evolves from a sphere into different shapes, such as a lemon, a conga drum, a cherry, a bowling pin, or a tubular shape for long and thick rods. The contact between the vesicle protrusion and the rod plays an important role in regulating the vesicle tubulation, membrane tension, and axial contact force on the rod. Our analysis provides a theoretical basis to understand a wide range of experiments on morphological transitions that occur in cellular packing of actin or microtubule bundles, mitotic cell division, and intracellular packing of carbon nanotubes.

Packing of flexible nanofibers in vesicles

Cellular packing of flexible nanofibers, including natural cytoskeletal microtubules, actin filaments, synthetic nanotubes and nanowires, is of fundamental interest to the understanding of a wide range of cell activities, including cell shape control, cell movement, cell division, and nano-cytotoxicity. Here, we perform molecular dynamics simulations and theoretical analysis to elucidate how the geometrical and mechanical properties of a flexible nanofiber influence its encapsulation within a lipid vesicle. Our analysis indicates that the packing morphology depends on the length and stiffness of the nanofiber, the initial configuration of the nanofiber–vesicle system and the pressure difference across the vesicle membrane. We establish a packing phase diagram based on three distinct vesicle morphologies in equilibrium, including a non-axisymmetric dumpling-shaped vesicle with a strongly curved nanofiber, a cherry-shaped vesicle with a tubular membrane protrusion enclosing a significant portion of the nanofiber, and an axisymmetric lemon-shaped vesicle with a pair of protruding tips induced by the encapsulated nanofiber.

Cellular packing, mechanical stress and the evolution of multicellularity.

The evolution of multicellularity set the stage for sustained increases in organismal complexity1-5. However, a fundamental aspect of this transition remains largely unknown: how do simple clusters of cells evolve increased size when confronted by forces capable of breaking intracellular bonds? Here we show that multicellular snowflake yeast clusters6-8 fracture due to crowding-induced mechanical stress. Over seven weeks (~291 generations) of daily selection for large size, snowflake clusters evolve to increase their radius 1.7-fold by reducing the accumulation of internal stress. During this period, cells within the clusters evolve to be more elongated, concomitant with a decrease in the cellular volume fraction of the clusters. The associated increase in free space reduces the internal stress caused by cellular growth, thus delaying fracture and increasing cluster size. This work demonstrates how readily natural selection finds simple, physical solutions to spatial constraints that limit the evolution of group size-a fundamental step in the evolution of multicellularity.

On the relationship between cellular and hemodynamic properties of the human brain cortex throughout adult lifespan

Establishing baseline MRI biomarkers for normal brain aging is significant and valuable for separating normal changes in the brain structure and function from different neurological diseases. In this paper for the first time we have simultaneously measured a variety of tissue specific contributions defining R2* relaxation of the gradient recalled echo (GRE) MRI signal in human brains of healthy adults (ages 22 to 74years) and related these measurements to tissue structural and functional properties. This was accomplished by separating tissue (R2t⁎) and extravascular BOLD contributions to the total tissue specific GRE MRI signal decay (R2⁎) using an advanced version of previously developed Gradient Echo Plural Contrast Imaging (GEPCI) approach and the acquisition and post-processing methods that allowed the minimization of artifacts related to macroscopic magnetic field inhomogeneities, and physiological fluctuations.Our data (20 healthy subjects) show that in most cortical regions R2t⁎ increases with age while tissue hemodynamic parameters, i.e. relative oxygen extraction fraction (OEFrel), deoxygenated cerebral blood volume (dCBV) and tissue concentration of deoxyhemoglobin (Cdeoxy) remain practically constant. We also found the important correlations characterizing the relationships between brain structural and hemodynamic properties in different brain regions. Specifically, thicker cortical regions have lower R2t⁎ and these regions have lower OEF.The comparison between GEPCI-derived tissue specific structural and functional metrics and literature information suggests that (a) regions in a brain characterized by higher R2t⁎ contain higher concentration of neurons with less developed cellular processes (dendrites, spines, etc.), (b) regions in a brain characterized by lower R2t⁎ represent regions with lower concentration of neurons but more developed cellular processes, and (c) the age-related increases in the cortical R2t⁎ mostly reflect the age-related increases in the cellular packing density.The baseline GEPCI-based biomarkers obtain herein could serve to help distinguish age-related changes in brain cellular and hemodynamic properties from changes which occur due to the neurodegenerative diseases.

Automation of cell production system for cellular phones using dual-arm robots

The demands placed on automation of cell production processes for IT products are becoming increasingly sophisticated. Dual-arm robots are drawing particular attention as a process solution because they offer flexibility and can work in a similar manner to a human operator. In this paper, we propose an automation system for cellular phone packing processes that uses two dual-arm robots. The applied robots are designed with specifications that meet the requirements of the cellular phone packing tasks. In addition, a robotic cell production system is proposed that applies a task allocation method to perform an efficient packing job for cellular phones. In particular, each task is assigned with the intention of reducing the takt time , which is the time taken to finish a single product in the production line and to avoid collisions between the two robots. Finally, we implement some of our results in a demonstration of a packing job that involves filling five unit boxes with seven kinds of accessories.

복수의 양팔로봇을 적용한 휴대폰 셀 생산시스템의 자동화

Demands for automation in the cell production process of IT products are becoming increasingly sophisticated. In particular, the dual ‐arm robot has drawn attention as a solution because it has a flexibility and works similarly to humans. In this paper, we propose an automation system for cellular phone packing processes using two dual‐arm robots. Applied robots are designed with specifications to meet the requirements of cellular phone packing jobs. In addition, a robotic cell production system is proposed by applying a method of task allocation for efficient packing of cellular phones. Specifically, a task is assigned to reduce takt‐time and to avoid collision between two robots. Finally, we discuss some experimental results that include the packing job of five unit boxes with seven kinds of accessories.Received 20 October 2014Revised 1 December 2014Accepted 10 December 2014

Diffusional kurtosis imaging: a promising technique for detecting microstructural changes in neural development and regeneration

Diffusional kurtosis imaging: a promising technique for detecting microstructural changes in neural development and regeneration

Simulation of Cellular Packing in Non-Proliferative Epithelia

Simulation of Cellular Packing in Non-Proliferative Epithelia

Simulation of cellular packing in non-proliferative epithelia

The physical laws governing the morphogenesis of biological tissues remain largely misunderstood. In particular, the role of the mechanical interactions occurring in this process needs to be better understood and studied. Inner follicular cells surrounding the oocytes of Ciona intestinalis form an epithelial monolayer resulting from an accretion process (without mitosis or apoptosis). This epithelium is elementary and useful for morphogenesis studies: the cells exhibit polygon packing with a specific but non-systematically repeatable topology (i.e. the distribution of pentagons, hexagons and heptagons changes). To understand the role of mechanical forces in tissue formation, we propose an innovative “2D spherical” model based on the physics of divided media. This approach simulates the cellular mechanical behavior and epithelium structuration by allowing cells to adopt a large variety of shapes and to self-organize in response to mechanical interactions. The numerical parameters considered in the model are derived from experimental data in order to perform pertinent and realistic simulations. The results obtained are compared to biological observations using the same counting method to characterize epithelium topology. Numerical and experimental data appear close enough to validate the model. It is then used for exploratory studies dealing with “Tissue Development Speed” variation, which is not easily attainable by experimentation. We show that the formation speed of the tissue influences its topology and hence its packing organization.

Penetration of anticancer drugs through tumour tissue as a function of cellular packing density and interstitial fluid pressure and its modification by bortezomib

BackgroundLimited penetration of anticancer drugs in solid tumours is a probable cause of drug resistance. Our previous results indicate that drug penetration depends on cellular packing density and adhesion between cancer cells.MethodsWe used epithelioid and round cell variants of the HCT-8 human colon carcinoma cell lines to generate tightly and loosely packed xenografts in nude mice. We measured packing density and interstitial fluid pressure (IFP) and studied the penetration of anti-cancer drugs through multilayered cell cultures (MCC) derived from epithelioid HCT-8 variants, and the distribution of doxorubicin in xenografts with and without pre-treatment with bortezomib.ResultsWe show lower packing density in xenografts established from round cell than epithelioid cell lines, with lower IFP in xenografts. There was better distribution of doxorubicin in xenografts grown from round cell variants, consistent with previous data in MCC. Bortezomib pre-treatment reduced cellular packing density, improved penetration, and enhanced cytotoxcity of several anticancer drugs in MCC derived from epithelioid cell lines. Pre-treatment of xenografts with bortezomib enhanced the distribution of doxorubicin within them.ConclusionsOur results provide a rationale for further investigation of agents that enhance the distribution of chemotherapeutic drugs in combination with conventional chemotherapy in solid tumours.

Analytical Results for Size-Topology Correlations in 2D Disk and Cellular Packings

Random tilings or packings in the plane are characterized by a size distribution of individual elements (domains) and by the statistics of neighbor relations between the domains. Most systems occurring in nature or technology have a unimodal distribution of both areas and number of neighbors. Empirically, strong correlations between these distributions have been observed and formulated as universal laws. Using only the local, correlation-free granocentric model approach with no free parameters, we construct accurate analytical descriptions for disk crystallization, size-topology correlations, and Lemaître's law.

Aerodynamic tests of new regular cellular packings for mass-transfer towers

The results of aerodynamic tests of new regular cellular packings for mass-transfer towers are reported. The key geometric and aerodynamic characteristics of the test cellular packings are compared with the characteristics of similarly designed regular packings that are widely used in the industry.

Hydraulic tests of cellular packing

The experimental unit on which the hydraulic tests of a new regular cellular (meshed) packing were performed is described. Based on the packing test data, we obtained graphical and analytical relationships which help determine the hydraulic resistance of the packing being sprinkled at various sprinkling densities for two most important hydrodynamic conditions applicable in practice.

Aerodynamics of cellular polymeric packing

created at the Moscow State University of Engineering Ecology (MGUIE), meet these requirements to a large extent. The packing is arranged in the tower in layers made from goffered (crimped) cellular flexible tubes, which ensures uniform distribution and good mixing of the liquid and gas phases. The experimental unit is shown schematically in Fig. 1. The working gas is air. The test regular cellular packing (RCP) 1 was placed in the experimental pipe 2 having an inner diameter of 100 mm. Before the packing layer, there was a hydrodynamic flow stabilization section whose length is eight times the diameter of the unit. The air was sucked into the pipe by the vacuum cleaner (pump) 3. In the course of the experiments, the air velocity (flow rate) in the pipe was measured by the thermoanemometer (hot-wire anemometer) 4. The pressure gradient Δp in the packing layer was measured by the differential spirit manometer 5. The air velocity w 0 calculated for the whole section of the empty unit varied from 2.55 m/sec to 4.46 m/sec. In Fig. 2, the hydraulic resistance Δp/H test data for the RCP-type polymeric packing is plotted against the air velocity w 0 . The hydraulic resistance data for polymeric Pall rings 25 mm and 50 mm in diameter supplied by The Pall Ring Company Ltd. [2] are also plotted there for comparison. As evident from Fig. 2, the hydraulic resistance of the RCP-type packing is close to that of Pall rings having a diameter of 50 mm. The new RCP-type packing, however, possesses four times larger specific surface (400 m 2 /m 3 ), a higher porosity (0.97 m 3 /m 3 ), and, consequently, a lower material content than Pall rings with a diameter of 50 mm whose specific surface is 100 m 2 /m 3 and porosity is 0.95 m 3 /m 3 . In comparison with Pall rings 25 mm in diameter (specific surface 209 m 2 /m 3 and porosity 0.91 m 3 /m 3 ), the RCP-type packing possesses twice as less hydraulic resistance, twice as large specific surface, and a higher porosity. The performed tests helped derive the relationship between the hydraulic resistance Δp/H (Pa/m) of dry polymeric RCP and the air velocity in the test w 0 (m/sec) range, which is described by the empirical equation:

Heat- and mass-transfer tests of cellular packing

Various schemes of water supply to industrial enterprises are examined. The geometric characteristics of a new regular cellular packing for heat- and mass-transfer processes are given. The experimental unit where the heat- and mass-transfer tests were performed is described. The systems of differential equations that describe the process of evaporative cooling of water in cooling towers are given. The test data are presented in the form a graph depicting the dependence of the evaporation number referred to the packing height on the relative air flow rate.

Correlation of MR Relative Cerebral Blood Volume Measurements with Cellular Density and Proliferation in High-Grade Gliomas: An Image-Guided Biopsy Study

As newer MR imaging techniques are used to assist with tumor grading, biopsy planning, and therapeutic response assessment, there is a need to relate the imaging characteristics to underlying pathologic processes. The aim of this study was to see how rCBV, a known marker of tumor vascularity, relates to cellular packing attenuation and cellular proliferation. Nine patients with histologically proved high-grade gliomas and 1 with a supratentorial PNET requiring an image-guided biopsy were recruited. Patients underwent a DSC study. The rCBV at the intended biopsy sites was determined by using a histogram measure to derive the mean, maximum, and 75th centile and 90th centile values. This measure was correlated with histologic markers of the MIB-1 labeling index (as a marker of glioma cell proliferation) and the total number of neoplastic cells in a high-power field (cellular packing attenuation). There was a good correlation between rCBV and MIB-1 by using all the measures of rCBV. The mean rCBV provided the best results (r = 0.66, P < .001). The only correlation with cellular packing attenuation was with the 90% centile (rCBV(90%), r = 0.36, P = .03). The increase in rCBV could be seen over 1 cm from the edge of enhancement in 4/10 cases, and at 2 cm in 1/10. rCBV correlated with cellular proliferation in high-grade gliomas but not with cellular packing attenuation. The increase in rCBV extended beyond the contrast-enhancing region in 50% of our patients.