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  • 1
    Electronic Resource
    Electronic Resource
    Physical forces and the mammalian cell. Edited by J. A. Frangos, Academic Press, 1993, 400 pp. (1994)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 40 (1994), S. 738-739 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690400417
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  • 2
    Electronic Resource
    Electronic Resource
    Measurement of bacterial random motility and chemotaxis coefficients: II. Application of single-cell-based mathematical model (1991)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 37 (1991), S. 661-672 
    Details
    ISSN: 0006-3592
    Keywords: bacterial chemotaxis ; Escherichia coli ; random motility ; diffusion chamber assay ; mathematical model ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A quantitative description of bacterial chemotaxis is necessary for making predictions about the migratory behavior of bacterial populations in applications such as biofilm development, release of genetically engineered bacteria into the environment, and in situ bioremediation technologies. The bacterial chemotactic response is characterized by a mathematical model which relates individual cell properties such as swimming speed and tumbling frequency to population parameters, specifically the random motility coefficient and the chemotactic sensitivity coefficient. Our model includes a nonlinear dependence of the chemotactic velocity on the attractant gradient as well as a dependence of the random motility coefficient on the temporal and spatial attractant gradients, both of which previous analyses have neglected. As we will show, these aspects are critical for interpreting the results from experiments like those performed in the stopped-flow diffusion chamber (SFDC) because the initial temporal and spatial gradients are very steep. Our analysis demonstrates that values for the random motility coefficient and chemotactic sensitivity coefficient can be obtained from experimental plots of net cell redistribution from initial conditions versus the square root of time. Values for these parameters are determined from experimental measurements of bacterial population distributions in the SFDC as described in the companion article. Using parameter values determined from independent experiments, μ = 1.1 ± 0.4 ± 10-5 cm2/s and χ0 = 8 ± 3 ± 10-5 cm2/s, excellent agreement is found between theoretically predicted bacterial density profiles and actual experimental profiles for Escherichia coli K12 responding to fucose over two orders of magnitude in initial attractant concentration. Thus, our model captures the concentration dependence of this behavioral response satisfactorily in terms of cell population parameters which are derived from individual cell properties and will therefore be useful for making predictions about the migratory behavior of bacterial populations in the environment.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260370708
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  • 3
    Electronic Resource
    Electronic Resource
    Measurement of individual cell migration parameters for human tissue cells (1992)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 38 (1992), S. 1092-1104 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: We present an approach for determining in vitro the means and distributions of a set of phenomenological parameters, including cell speed and persistence time, which can be used to evaluate the effect of isotropic variations in the extracellular environment on the motility of human tissue cells. Using time-lapse videomicroscopy and semi-automated image analysis, we tracked the paths traveled by slow-moving, isolated human vascular smooth muscle cells over 48 hours on surfaces of petri dishes coated with 10 μg/mL of the adhesive extracellular matrix proteins type IV collagen, fibronectin or laminin. By applying a persistent random walk model to experimental data for mean-squared displacement as a function of time for these cells, we rigorously distinguished individual cells with different motile characteristics not obvious based on qualitative comparisons between the structures of individual cell paths. We also positively identified the presence of immotile cells. Based on the behavior of 34 to 77 cells on each substrate, we found mean cell speeds and persistence times on the order of 10 micron/h and 3 hours, respectively, on all three ECM substrates, while the fraction of motile cells varied from 65% on laminin to 78% on collagen. On all three surfaces experimental number distributions of speed and persistence time could be described by normal and exponential waiting time distributions, respectively. Our approach provides a framework for addressing questions concerning the mechanistic relationship between cellular and environmental properties and cell motility.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690380712
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  • 4
    Electronic Resource
    Electronic Resource
    Model for ER chaperone dynamics and secretory protein interactions (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 1443-1453 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Expression of proteins in eucaryotic systems is often the only way to ensure the correct folding and processing necessary for protein function. Heterologous proteins, however, are commonly retained in the secretory pathway, so that secreted product yield is low despite a high level of transcription. A major limiting step in protein secretion is protein folding in the lumen of the endoplasmic reticulum. This process is assisted by accessory macromolecules resident in this compartment, including chaperones such as the hsp70 homologue binding protein (BiP). Although induction of foreign proteins in yeast initially elicits a transient increase in local chaperone concentration, long-term protein expression lowers both chaperone and secreted product. A mechanistic model that can account for the experimentally observed role of BiP in secretion and the effects of BiP overexpression on the secretory pathway is described here. The model predicts that equimolar synthesis of chaperone and foreign protein should optimize protein secretion.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420525
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  • 5
    Electronic Resource
    Electronic Resource
    Measurement of bacterial random motility and chemotaxis coefficients: I. Stopped-flow diffusion chamber assay (1991)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 37 (1991), S. 647-660 
    Details
    ISSN: 0006-3592
    Keywords: bacterial chemotaxis ; Escherichia coli ; motility, random ; diffusion chamber assay ; mathematical model ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Bacterial chemotaxis, the directed movement of a cell population in response to a chemical gradient, plays a critical role in the distribution and dynamic interaction of bacterial populations in nonmixed systems. Therefore, in order to make reliable predictions about the migratory behavior of bacteria within the environment, a quantitative characterization of the chemotactic response in terms of intrinsic cell properties is needed.The design of the stopped-flow diffusion chamber (SFDC) provides a well-characterized chemical gradient and reliable method for measuring bacterial migration behavior. During flow through the chamber, a step change in chemical concentration is imposed on a uniform suspension of bacteria. Once flow is stopped, diffusion causes a transient chemical gradient to develop, and bacteria respond by forming a band of high cell density which travels toward higher concentrations of the attractant. Changes in bacterial spatial distributions observed through light scattering are recorded on photomicrographs during a 10-min period. Computer-aided image analysis converts absorbance of the photographic negatives to a digital representation of bacterial density profiles. A mathematical model (part II) is used to quantitatively characterize these observations in terms of intrinsic cell parameters: a chemotactic sensitivity coefficient, μ0, from the aggregate cell density accumulated in the band and a random motility coefficient, μ, from population dispersion in the absence of a chemical gradient.Using the SFDC assay and an individual-cell-based mathematical model, we successfully determined values for both of these population parameters for Escherichia coli K12 responding to fucose. The values obtained were μ = 1.1 ± 0. 4 × 10-5 cm2/s and χo = 8 ± 3 ± 10-5 cm2/s. We have demonstrated a method capable of determining these parameter values from the now validated mathematical model which will be useful for predicting bacterial migration in application systems.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260370707
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  • 6
    Electronic Resource
    Electronic Resource
    Quantification of bacterial chemotaxis by measurement of model parameters using the capillary assay (1986)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 28 (1986), S. 1178-1190 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The capillary assay for quantitative characterization of bacterial motility and chemotaxis is analyzed in terms of a mathematical model for cell population migration, in order to determine values for the cell random motility coefficient, μ and the cell chemotaxis coefficient, χ. The analysis involves both analytical perturbation methods and numerical finite-difference techniques. Transient cell density profiles within the capillary tube are determined as they depend upon μ and χ, providing a means for estimating μ and χ from the common protocol measurements of cell accumulation in the tube at specified observation times. The effects of extraneous factors such as assay geometry, stimulus diffusivity, bacterial density, and observation time are thus separated from the intrinsic cell-stimulus interaction and response. This allows independent population measurements of cell chemosensory movement properties to be extrapolated to situations involving growth and competition of populations, for purposes of better understanding microbial population dynamics in systems of biotechnological and microbial ecological importance.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260280808
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  • 7
    Electronic Resource
    Electronic Resource
    Cell transport in the millipore filter assay (1989)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 35 (1989), S. 459-465 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690350314
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  • 8
    Electronic Resource
    Electronic Resource
    Engineering dynamics of growth factors and other therapeutic ligands (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 52 (1996), S. 61-80 
    Details
    ISSN: 0006-3592
    Keywords: growth factors ; receptors ; trafficking ; mammalian cells ; cell engineering ; cytokine ligands ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Peptide growth factors and other receptor-binding cytokine ligands are of interest in contemporary molecular health care approaches in applications such as wound healing, tissue regeneration, and gene therapy. Development of effective technologies based on operation of these regulatory molecules requires an ability to deliver the ligands to target cells in a reliable and well-characterizable manner. Quantitative information concerning the fate of peptide ligands within tissues is necessary for adequate interpretation of experimental observations at the tissue level and for truly rational engineering design of ligand-based therapies. To address this need, we are undertaking efforts to elucidate effects of key molecular and cellular parameters on temporal and spatial distribution of cytokines in cell population and cell/matrix systems. In this article we summarize some of our recent findings on dynamics of growth factor depletion by cellular endocytic trafficking, growth factor transport through cellular matrices, and growth factor production and release by autocrine cell systems. © 1996 John Wiley & Sons, Inc.
    Additional Material: 18 Ill.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Intracellular receptor/ligand sorting based on endosomal retention components (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 51 (1996), S. 281-297 
    Details
    ISSN: 0006-3592
    Keywords: endosome ; sorting ; retention ; epidermal growth factor ; transforming growth factor α ; epidermal growth factor receptor ; intracellular trafficking ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Endocytosed molecules are sorted in endosomes to different cellular destinations (e.g., to lysosomes or to the plasma membrane). Diverse endosomal sorting results have been reported for different ligands and receptors in a variety of cell types, but the general principles governing these sorting outcomes are not well understood. For example, we observed a wide range of sorting outcomes with the epidermal growth factor (EGF)/receptor system in fibroblasts using several members of the EGF family and site-directed ligand and receptor mutants. In this article we describe a mechanistic mathematical model of endosomal sorting based on the hypothesis that receptors may be selectively retained by the endosomal sorting apparatus and that this process may be modulated by receptor occupancy. Our results show that this single mechanism can account for the wide variety of observed sorting outcomes. By providing a conceptual framework for understanding endosomal sorting, this model not only helps interpret our experimental results for the EGF/receptor system, but also provides some insight into the principles governing sorting. For example, the model predicts that the influence of selective endosomal retention of receptor/ligand complexes is seen in deviations of ligand sorting outcomes from pure fluid phase sorting behavior. Furthermore, the model suggests that selective endosomal retention of complexes within endosomes gives rise to three sorting regimes characterized by distinguishable qualitative trends in the dependence of ligand sorting fractions on intracellular ligand concentrations. © 1996 John Wiley & Sons, Inc.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
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