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1.
BMC Cancer ; 20(1): 1201, 2020 Dec 07.
Article in English | MEDLINE | ID: mdl-33287759

ABSTRACT

BACKGROUND: The mechanisms of action and efficacy of cisplatin and paclitaxel at cell population level are well studied and documented, however the localized spatio-temporal effects of the drugs are less well understood. We explore the emergence of spatially preferential drug efficacy resulting from variations in mechanisms of cell-drug interactions. METHODS: 3D spheroids of HeLa-C3 cells were treated with drugs, cisplatin and paclitaxel. This was followed by sectioning and staining of the spheroids to track the spatio-temporal apoptotic effects of the drugs. A mechanistic drug-cell interaction model was developed and simulated to analyse the localized efficacy of these drugs. RESULTS: The outcomes of drug actions on a local cell population was dependant on the interactions between cell repair probability, intracellular drug concentration and cell's mitosis phase. In spheroids treated with cisplatin, drug induced apoptosis is found to be scattered throughout the volume of the spheroids. In contrast, effect of paclitaxel is found to be preferentially localized along the periphery of the spheroids. Combinatorial treatments of cisplatin and paclitaxel result in varying levels of cell apoptosis based on the scheduling strategy. CONCLUSIONS: The preferential action of paclitaxel can be attributed to the cell characteristics of the peripheral population. The model simulations and experimental data show that treatments initiated with paclitaxel are more efficacious due to the cascading of spatial effects of the drugs.


Subject(s)
Antineoplastic Agents/therapeutic use , Imaging, Three-Dimensional/methods , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Spheroids, Cellular/metabolism , Apoptosis , Cell Proliferation , Female , HeLa Cells , Humans , Transfection
2.
J Theor Biol ; 482: 109994, 2019 12 07.
Article in English | MEDLINE | ID: mdl-31487498

ABSTRACT

Morphological changes in bacterial biofilm structures arise from the fluid-structure interactions between the biofilm and the surrounding fluid. Depending on the magnitude of the force acting on the structure, the bacteria rearrange to attain an equilibrium shape or get washed away by the moving fluid. Understanding the dynamics behind the evolution of such equilibrium or failed states can aid in development of tools for biofilm removal or eradication. We develop a Glazier-Graner-Hogeweg method-based model to explore the collective evolution of biofilm morphology arising from cell-cell and cell-fluid interactions. We show that low adherence and high motility of the cells leads to sloughing of biofilms. Also, streamers are found to form under laminar flow conditions in tightly packed biofilms. In mixed species biofilms, we found that a species with less cell-cell binding affinity gets eroded faster than its counterpart. Therefore, we hypothesize that in nature these less-adherent species should be present encapsulated within the biofilm structure to maximize their chances of survival.


Subject(s)
Bacterial Adhesion/physiology , Biofilms/growth & development , Hydrodynamics , Stress, Mechanical , Computer Simulation , Pseudomonas aeruginosa/physiology , Shear Strength/physiology
3.
Article in English | MEDLINE | ID: mdl-29463543

ABSTRACT

Segregation of bacteria based on their metabolic activities in biofilms plays an important role in the development of antibiotic resistance. Mushroom-shaped biofilm structures, which are reported for many bacteria, exhibit topographically varying levels of multiple drug resistance from the cap of the mushroom to its stalk. Understanding the dynamics behind the formation of such structures can aid in design of drug delivery systems, antibiotics, or physical systems for removal of biofilms. We explored the development of metabolically heterogeneous Pseudomonas aeruginosa biofilms using numerical models and laboratory knockout experiments on wild-type and chemotaxis-deficient mutants. We show that chemotactic processes dominate the transformation of slender and hemispherical structures into mushroom structures with a signature cap. Cellular Potts model simulation and experimental data provide evidence that accelerated movement of bacteria along the periphery of the biofilm, due to nutrient cues, results in the formation of mushroom structures and bacterial segregation. Multidrug resistance of bacteria is one of the most threatening dangers to public health. Understanding the mechanisms of the development of mushroom-shaped biofilms helps to identify the multidrug-resistant regions. We decoded the dynamics of the structural evolution of bacterial biofilms and the physics behind the formation of biofilm structures as well as the biological triggers that produce them. Combining in vitro gene knockout experiments with in silico models showed that chemotactic motility is one of the main driving forces for the formation of stalks and caps. Our results provide physicists and biologists with a new perspective on biofilm removal and eradication strategies.


Subject(s)
Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/metabolism , Pseudomonas aeruginosa/cytology
4.
Sci Rep ; 5: 11652, 2015 Jun 26.
Article in English | MEDLINE | ID: mdl-26113515

ABSTRACT

Silica deposition by diatoms, a common component of the phytoplankton, has attracted considerable interest given the importance in ecology and materials science. There has recently been a great deal of research into the biological control of biosilicifcation, yet the in vivo physical and chemical effects have not been quantitatively investigated. We have grown the marine diatom Thalassiosira pseudonana in batch culture at three temperatures (14°, 18°, and 23 °C). We observed three distinct temperature-dependent growth phases. The morphology of silica was investigated using scanning electron microscopy followed by image analysis and supervised learning. The silica in the valves of the same species showed different structures: a mesh-like pattern in silicon-rich cultures and a tree-like pattern in silicon-limited cultures. Moreover, temperature affected this silica pattern, especially in silicon-limited cultures. We conclude that cells grown at 14 °C and 18 °C divide more successfully in Si-limited conditions by developing a tree-like pattern (lower silicification).

5.
BMC Infect Dis ; 11: 118, 2011 May 11.
Article in English | MEDLINE | ID: mdl-21569307

ABSTRACT

BACKGROUND: The transmission through contacts among MSM (men who have sex with men) is one of the dominating contributors to HIV prevalence in industrialized countries. In Amsterdam, the capital of the Netherlands, the MSM risk group has been traced for decades. This has motivated studies which provide detailed information about MSM's risk behavior statistically, psychologically and sociologically. Despite the era of potent antiretroviral therapy, the incidence of HIV among MSM increases. In the long term the contradictory effects of risk behavior and effective therapy are still poorly understood. METHODS: Using a previously presented Complex Agent Network model, we describe steady and casual partnerships to predict the HIV spreading among MSM. Behavior-related parameters and values, inferred from studies on Amsterdam MSM, are fed into the model; we validate the model using historical yearly incidence data. Subsequently, we study scenarios to assess the contradictory effects of risk behavior and effective therapy, by varying corresponding values of parameters. Finally, we conduct quantitative analysis based on the resulting incidence data. RESULTS: The simulated incidence reproduces the ACS historical incidence well and helps to predict the HIV epidemic among MSM in Amsterdam. Our results show that in the long run the positive influence of effective therapy can be outweighed by an increase in risk behavior of at least 30% for MSM. CONCLUSION: We recommend, based on the model predictions, that lowering risk behavior is the prominent control mechanism of HIV incidence even in the presence of effective therapy.


Subject(s)
HIV Infections/epidemiology , HIV Infections/psychology , Homosexuality, Male/psychology , Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , Humans , Incidence , Male , Netherlands/epidemiology , Risk-Taking , Sexual Behavior , Sexual Partners
6.
Philos Trans A Math Phys Eng Sci ; 367(1898): 2691-703, 2009 Jul 13.
Article in English | MEDLINE | ID: mdl-19487205

ABSTRACT

Human immunodeficiency virus (HIV) is recognized to be one of the most destructive pandemics in recorded history. Effective highly active antiretroviral therapy and the availability of genetic screening of patient virus data have led to sustained viral suppression and higher life expectancy in patients who have been infected with HIV. The sheer complexity of the disease stems from the multiscale and highly dynamic nature of the system under study. The complete cascade from genome, proteome, metabolome and physiome to health forms a multidimensional system that crosses many orders of magnitude in temporal and spatial scales. Understanding, quantifying and handling this complexity is one of the biggest challenges of our time, which requires a highly multidisciplinary approach. In order to supply researchers with an interactive framework and to provide the medical professional with appropriate tools and information for making a balanced and reliable clinical decision, we have developed 'ViroLab', a collaborative decision-support system (http://www.virolab.org/). ViroLab contains computational models that cover various spatial and temporal scales from atomic-level interactions in nanoseconds up to sociological interactions on the epidemiological level, spanning years of disease progression. ViroLab allows for personalized drug ranking. It is on trial in six hospitals and various virology and epidemiology laboratories across Europe.


Subject(s)
Antiretroviral Therapy, Highly Active , HIV Infections , Disease Progression , Europe , Humans , Male , Software
7.
Phys Rev E Stat Nonlin Soft Matter Phys ; 75(4 Pt 2): 046116, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17500970

ABSTRACT

We present a cellular automaton (CA) model for simulating the complex dynamics of stock markets. Within this model, a stock market is represented by a two-dimensional lattice, of which each vertex stands for a trader. According to typical trading behavior in real stock markets, agents of only two types are adopted: fundamentalists and imitators. Our CA model is based on local interactions, adopting simple rules for representing the behavior of traders and a simple rule for price updating. This model can reproduce, in a simple and robust manner, the main characteristics observed in empirical financial time series. Heavy-tailed return distributions due to large price variations can be generated through the imitating behavior of agents. In contrast to other microscopic simulation (MS) models, our results suggest that it is not necessary to assume a certain network topology in which agents group together, e.g., a random graph or a percolation network. That is, long-range interactions can emerge from local interactions. Volatility clustering, which also leads to heavy tails, seems to be related to the combined effect of a fast and a slow process: the evolution of the influence of news and the evolution of agents' activity, respectively. In a general sense, these causes of heavy tails and volatility clustering appear to be common among some notable MS models that can confirm the main characteristics of financial markets.

8.
J Biomech ; 39(5): 873-84, 2006.
Article in English | MEDLINE | ID: mdl-16488226

ABSTRACT

The complex nature of blood flow in the human arterial system is still gaining more attention, as it has become clear that cardiovascular diseases localize in regions of complex geometry and complex flow fields. In this article, we demonstrate that the lattice Boltzmann method can serve as a mesoscopic computational hemodynamic solver. We argue that it may have benefits over the traditional Navier-Stokes techniques. The accuracy of the method is tested by studying time-dependent systolic flow in a 3D straight rigid tube at typical hemodynamic Reynolds and Womersley numbers as an unsteady flow benchmark. Simulation results of steady and unsteady flow in a model of the human aortic bifurcation reconstructed from magnetic resonance angiography, are presented as a typical hemodynamic application.


Subject(s)
Aorta, Abdominal/physiology , Blood Flow Velocity/physiology , Models, Cardiovascular , Systole/physiology , Computer Simulation , Humans
9.
J Chem Phys ; 123(8): 084105, 2005 Aug 22.
Article in English | MEDLINE | ID: mdl-16164280

ABSTRACT

To learn about the basic aspects of nanoscale spherical molecular shells during their formation, spherically curved two-dimensional N-particle Lennard-Jones systems are simulated, studying curvature evolution paths at zero temperature. For many N values (N<800) equilibrium configurations are traced as a function of the curvature radius R. Sharp jumps for tiny changes in R between trajectories with major differences in topological structure correspond to avalanche-like transitions. For a typical case, N=25, equilibrium configurations fall on smooth trajectories in state space which can be traced in the E-R plane. The trajectories show up with local energy minima, from which growth in N at steady curvature can develop.


Subject(s)
Chemistry, Physical/methods , Computer Simulation , Models, Statistical , Models, Theoretical , Molecular Conformation , Temperature , Thermodynamics
10.
Phys Rev E Stat Nonlin Soft Matter Phys ; 66(4 Pt 2): 046110, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12443262

ABSTRACT

The Yang-Lee zeros of the Q-state Potts model on recursive lattices are studied for noninteger values of Q. Considering one-dimensional (1D) lattice as a Bethe lattice with coordination number equal to 2, the location of Yang-Lee zeros of 1D ferromagnetic and antiferromagnetic Potts models is completely analyzed in terms of neutral periodical points. Three different regimes for Yang-Lee zeros are found for Q>1 and 01. Complex magnetic field metastability regions are studied for the Q>1 and 0

11.
Phys Rev Lett ; 88(23): 234501, 2002 Jun 10.
Article in English | MEDLINE | ID: mdl-12059367

ABSTRACT

The role of stagnant zones in hydrodynamic dispersion is studied for creeping flow through a fixed bed of spherical permeable particles, covering several orders of characteristic time and length scales associated with fluid transport. Numerical simulations employ a hierarchical model to cope with the different temporal and spatial scales, showing good agreement with our experimental results on diffusion-limited mass transfer, transient, and asymptotic longitudinal dispersion. These data demonstrate that intraparticle liquid holdup in macroscopically homogeneous porous media clearly dominates over contributions caused by the intrinsic flow field heterogeneity and boundary-layer mass transfer.

12.
Philos Trans A Math Phys Eng Sci ; 360(1792): 521-34, 2002 Mar 15.
Article in English | MEDLINE | ID: mdl-16214692

ABSTRACT

We have studied hydrodynamic dispersion in single-phase incompressible liquid flow through a fixed bed made of spherical, permeable (porous) particles. The observed behaviour was contrasted with the corresponding fluid dynamics in a random packing of impermeable (non-porous) spheres with an interparticle void fraction of 0.37. Experimental data were obtained in the laminar flow regime by pulsed field gradient nuclear magnetic resonance and were complemented by numerical simulations employing a hierarchical transport model with a discrete (lattice Boltzmann) interparticle flow field. Finite-size effects in the simulation associated with the spatial discretization of support particles or dimension and boundaries of the bed were minimized and the simulation results are in reasonable agreement with experiment.


Subject(s)
Colloids/chemistry , Diffusion , Magnetic Resonance Spectroscopy/methods , Models, Chemical , Rheology/methods , Solutions/chemistry , Biological Transport , Computer Simulation , Kinetics , Motion , Numerical Analysis, Computer-Assisted , Particle Size , Porosity , Pressure , Quantum Theory
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