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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 745 (1994), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 35 (1989), S. 459-465 
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: During inflammation, leukocytes cross the blood vessel wall and migrate to the inflammatory site in response to gradients of diffusible chemical attractants produced there. This directed migration response to a chemical gradient, termed chemotaxis, can be studied experimentally in the Millipore filter assay. We have applied a mathematical model to analyze cell population migration in the assay in terms of two parameters analogous to molecular transport coefficients. The random motility coefficient, μ, reflects the cell response to uniform concentrations of chemical attractant, while the chemotaxis coefficient, χ, reflects the response to a concentration gradient. We have measured μ and χ by comparing theoretical cell density profiles to those measured in the assay. Both parameters vary as a function of the attractant concentration; μ ranges from 10-10-10-9 cm2/s and χ ranges from 10-100 cm2/s.M for the attractant tested. These values agree with ones predicted from a priori theoretical relationships for μ and χ. Quantitation of the Millipore filter assay provides a framework for the quantitation of analogous cell transport systems such as a composite assay simulating cell migration across the vessel wall.
    Additional Material: 10 Ill.
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  • 3
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 41 (1995), S. 691-700 
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Transport of small molecules in heterogeneous materials can be an important factor in many engineering and biological applications. This study focuses on the diffusion of cellular nutrients in an immobilized cell system. A Monte Carlo simulation technique is used to describe the diffusion of small molecules in a variety of simulated cellular structures. Diffusivity predictions are in close agreement with experimental values as well as with theoretical bounds reported in the literature. It is revealed that effective diffusivities are highly dependent on the diffusivities of the species in the various phases and on the volume fraction of cells. The spatial arrangement of the cells, however, has no apparent effect on the predicted diffusivity for the range of conditions investigated.
    Additional Material: 10 Ill.
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 49 (1996), S. 223-227 
    ISSN: 0006-3592
    Keywords: immobilized cells ; diffusivity measurement ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A simple correlation method has been developed to predict effective diffusivities of small molecules in heterogeneous materials such as immobilized cell systems. This correlation uses a single diffusivity measurement at one cell volume fraction to predict diffusivities for any other volume fraction of cell. The method has been applied to 20 sets of published diffusivity measurements in immobilized cell systems and accurately predicts affective diffusivities of molecules for the full range of cell fractions. It may also be used to predict effective diffusivities in heterogeneous materials in which the diffusivity of a molecule in each phase and the volume fraction of each phase are known. © 1996 John Wiley & Sons, Inc.
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 50 (1996), S. 452-461 
    ISSN: 0006-3592
    Keywords: cytoskeletal dynamics ; time series analysis ; anticorrelation ; cell motility ; neurites ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The controlled extension of neurites is essential not only for nervous system development, but also for effective nerve regeneration after injury. This process is critically dependent on microtubule assembly since axons fail to elongate in the presence of drugs which disrupt normal assembly dynamics. For this reason, neurite outgrowth is potentially controllable by manipulation of the assembly state of the intracellular array of microtubules. Therefore, understanding how microtubule assembly dynamics and neurite outgrowth are coupled, in the absence of drugs, can lend valuable insight into the control and guidance of the outgrowth process. In the present study we characterized the stochastic dynamics of neurite outgrowth and its corresponding microtubule array, which advances concomitantly with the advance of the nerve growth cone, the highly motile structure at the terminus of the growing neurite, using reported fluorescent microscopic image sequences (Tanaka and Kirschner, 1991, J. Cell Biol. 115:345-363). Although previously modeled as an uncorrelated random walk, the stochastic advance of the growth cone was found to be anticorrelated over a time scale of ∼4 min, meaning that growth cone advances tended to be followed by growth cone retractions ∼4 min later. The observed anticorrelation most likely reflects the periodic stops and starts of neurite outgrowth that have been reported anecdotally. A strikingly similar pattern of anticorrelation was also identified in the advance of the growth cone's microtubule array. Cross-correlation analysis showed that growth cone dynamics tended to precede microtubule dynamics on a time scale of ∼0-2 min, while microtubules tended to precede growth cone dynamics on a ∼0-20-s time scale, indicating a close temporal coupling between microtubule and growth cone dynamics. Finally, the scaling of the mean-squared displacements with time for both the growth cone and microtubules suggested a fractional Brownian motion model which accounts for the observed anticorrelation of growth cone and microtubule advance. © 1996 John Wiley & Sons, Inc.
    Additional Material: 6 Ill.
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  • 6
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 32 (1995), S. 187-204 
    ISSN: 0886-1544
    Keywords: neuronal growth cone migration ; filopodial dynamics ; simulation model ; computer graphics ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The neuronal growth cone plays a fundamental role in nerve development and regeneration. A sensory-motile structure, it determines the path of axonal extension through its interactions with the extracellular environment, ultimately directing the formation of functional connections in the nervous system. Though several mechanisms of interaction have been proposed, these have been difficult to describe quantitatively due to the complexity of growth cone behavior, as manifested in the randomly and rapidly changing shape of the growth cone. The application of mathematical techniques to model growth cone shape and motility in terms of underlying processes represents a promising approach with untapped potential for helping to unravel this complexity while revealing new insights into axonal pathfinding events. This paper presents a simulation model for filopodial dynamics, a primary feature of the motile growth cone. The model produces realizations of dynamic filopodial structure on representative growth cones for a given set of model parameters, which include the rates of filopodial initiation, extension, and retraction, filopodial length at maximum extension, and angular orientation. These parameters are based on recent experimental characterization of filopodial dynamics [Buettner et al., 1994: Dev. Biol. 163:407-422]. The mathematical relationship between the model parameters and average filopodial number and length per growth cone is described, and the contribution of individual parameters to overall filopodial morphology is illustrated both visually and numerically. In addition, the model is used to simulate filopodial encounter with a target for various conditions of filopodial dynamics. The result is characterized in terms of a mean encounter time for a population of growth cones and provides an indication of the effect of individual parameters of filopodial dynamics on the encounter process. Future experimental testing will be required to develop the model further. However, in its current form, the model enables a first approximation analysis of many hypotheses of growth cone migration and pathfinding and offers insight into the the underlying mechanismes of nerve growth and regeneration. © 1995 Wiley-Liss, Inc.
    Additional Material: 10 Ill.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Annals of biomedical engineering 23 (1995), S. 268-286 
    ISSN: 1573-9686
    Keywords: Microtubule dynamic instability ; Probability models ; Simulation ; Nerve regeneration ; Neuroengineering
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract The process of neurite outgrowth is critically dependent on proper microtubule assembly. However, characterizing the dynamics of microtubule assembly and their quantitative relationship to neurite outgrowth is a difficult task. The difficulty can be reduced by using time series analysis which has broad application in characterizing the dynamics of stochastic, or “noisy,” behaviors. Here we apply time series analysis to quantitatively compare simulated microtubule assembly and neurite outgrowth in vitro. Microtubule length life histories were simulated assuming constant growth and shrinkage rates coupled with random selection of growth and shrinkage times, a formulation based on the dynamic instability model of microtubules assembly. Net length displacements of simulated microtubules were calculated at discrete, evenly spaced times, and the resulting time series were characterized by both spectral and autocorrelation analysis. Depending on the sampling rate and the dynamic parameters, simulated microtubules exhibited significant autocorrelation and periodicity. To make a comparison to neurite outgrowth, we characterized the dynamic behavior of simulated microtubule populations and found it was not significantly different from that of single microtubules. The net displacements of rat superior cervical ganglion neurite tips were measured and characterized using time series methods. Their behavior was consistent with the microtubule dynamics for appropriate simulation parameters and sampling rates. Our results show that time series analysis can provide a useful tool for quantitative characterization of microtubule dynamics and neurite outgrowth and for assessing the relationship between them.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 1127-1138 
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Dynamic projections from the surface of many motile cell types provide for variable contact with the extracellular environment and can be important in regulating cell migration events. For example, during nerve development and regeneration, the sensory motile tip of the axon exhibits long, slender filopodia projecting from the growth cone periphery. Extension and retraction of these filopodia continually remodel the points of contact between axon and surroundings. Experimental studies show that filopodial contact with specific extracellular features can guide subsequent growth cone migration, suggesting a potentially important means of engineering nerve growth to repair nerve injury or construct biological neural networks. A simulation model is presented of the dynamic filopodial structure on the nerve growth cone based on recent experimental characterization. The model is analyzed to obtain quantitative relationships between average filopodial characteristics, which are commonly measured experimental quantities, and the underlying parameters of individual filopodium dynamics. It is then applied to simulate encounter between a growth cone and its target due to filopodial dynamics alone. Filopodial contribution to growth cone-target encounter is summarized in terms of a mean encounter time that is reminiscent of a first passage time for a diffusing particle. The parametric relationships in this study provide a basis for further investigation of filopodial-mediated mechanisms in nerve growth and other cellular processes.
    Additional Material: 10 Ill.
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  • 9
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 1434-1442 
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Microtubules are linear polymers of the cytoskeleton that serve to organize the cytoplasm of eukaryotic cells. Understanding how microtubule polymers self-assemble is important in biotechnology, including the development of novel cancer therapies and proper guidance of regenerating neurons. The assembly of microtubules occurs by a unique process whereby an individual microtubule undergoes abrupt and apparently stochastic switching between alternating steady states of growth and shrinkage, a phenomenon known as microtubule dynamic instability. To characterize these oscillations spectral (frequency-domain) analysis, commonly used in engineering for system identification, was applied. Power spectra of the individual microtubule-length life histories revealed oscillations within growth phases, directly reflecting acceleration and deceleration in the growth process. These fluctuations were not accounted for by the standard two-state model commonly used in the analysis of microtubule assembly, despite the inclusion of simulated measurement error in the model. Thus, the spectral analysis of microtubule assembly permitted characterization of assembly process dynamics independent of particular assembly models, and as such represents a powerful analytical framework within which to study microtubule dynamic instability and assess its function in vivo.
    Additional Material: 8 Ill.
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  • 10
    Publication Date: 1994-04-01
    Print ISSN: 1063-651X
    Electronic ISSN: 1095-3787
    Topics: Physics
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