George Oster - Academia.edu (original) (raw)
Papers by George Oster
Biophysical journal, Jan 1, 2005
Two theoretical formalisms are widely used in modeling mechanochemical systems such as protein mo... more Two theoretical formalisms are widely used in modeling mechanochemical systems such as protein motors: continuum Fokker-Planck models and discrete kinetic models. Both have advantages and disadvantages. Here we present a “finite volume” procedure to solve Fokker-Planck equations. The procedure relates the continuum equations to a discrete mechanochemical kinetic model while retaining many of the features of the continuum formulation. The resulting numerical algorithm is a generalization of the algorithm developed previously by Fricks, Wang, and Elston through relaxing the local linearization approximation of the potential functions, and a more accurate treatment of chemical transitions. The new algorithm dramatically reduces the number of numerical cells required for a prescribed accuracy. The kinetic models constructed in this fashion retain some features of the continuum potentials, so that the algorithm provides a systematic and consistent treatment of mechanical-chemical responses such as load-velocity relations, which are difficult to capture with a priori kinetic models. Several numerical examples are given to illustrate the performance of the method.
Proceedings of The National Academy of Sciences, 2001
Recent experiments have provided new quantitative measurements of the rippling phenomenon in fiel... more Recent experiments have provided new quantitative measurements of the rippling phenomenon in fields of developing myxobacteria cells. These measurements have enabled us to develop a mathematical model for the ripple phenomenon on the basis of the biochemistry of the C-signaling system, whereby individuals signal by direct cell contact. The model quantitatively reproduces all of the experimental observations and illustrates how
European Biophysics Journal With Biophysics Letters, 1996
Many cell movements appear to be driven by the polymerization of actin. Here we show how the forc... more Many cell movements appear to be driven by the polymerization of actin. Here we show how the force of polymerization can be generated by the thermal motions of the actin filaments near the sites of polymerization. We apply the model to explain the observations that the lamellipodial cytoskeleton is organized into an orthogonal network interspersed with filopodial protrusions, and that
... THE VELIGER © CMS, Inc., 1986 A Model for Shell Patterns Based on Neural Activity by BARD ERM... more ... THE VELIGER © CMS, Inc., 1986 A Model for Shell Patterns Based on Neural Activity by BARD ERMENTROUT ... 28, No.4 a b c Figure 1 Three fundamental classes of shell pigment markings on Bankivia fasciata: a, longitudinal bands; b, incremental lines; c, oblique stripes. ...
Trends in cell biology, 2003
Three protein motors have been unambiguously identified as rotary engines: the bacterial flagella... more Three protein motors have been unambiguously identified as rotary engines: the bacterial flagellar motor and the two motors that constitute ATP synthase (F(0)F(1) ATPase). Of these, the bacterial flagellar motor and F(0) motors derive their energy from a transmembrane ion-motive force, whereas the F(1) motor is driven by ATP hydrolysis. Here, we review the current understanding of how these protein motors convert their energy supply into a rotary torque.
Experimental and Theoretical Advances in Biological Pattern Formation, 1993
Institute for Nonlinear Science, 1996
Using molecular dynamics, we study the unbinding of ATP in F 1 -ATPase from its tight binding sta... more Using molecular dynamics, we study the unbinding of ATP in F 1 -ATPase from its tight binding state to its weak binding state. The calculations are made feasible through use of interpolated atomic structures from Wang and Oster [Nature 1998, 396: 279-282]. These structures are applied to atoms distant from the catalytic site. The forces from these distant atoms gradually drive a large primary region through a series of sixteen equilibrated steps that trace the hinge bending conformational change in the b-subunit that drives rotation of g-subunit. As the rotation progresses, we find a sequential weakening and breaking of the hydrogen bonds between the ATP molecule and the a-and b-subunits of the ATPase. This finding agrees with the ''binding-zipper'' model Wang, Biochim. Biophys. Acta 2000, 1458: 482-510.] In this model, the progressive formation of the hydrogen bonds is the energy source driving the rotation of the g-shaft during hydrolysis. Conversely, the corresponding sequential breaking of these bonds is driven by rotation of the shaft during ATP synthesis. Our results for the energetics during rotation suggest that the nucleotide's coordination with Mg 21 during binding and release is necessary to account for the observed high efficiency of the motor.
Human keratinocytes migrate towards the negative pole in DC electric fields of physiological stre... more Human keratinocytes migrate towards the negative pole in DC electric fields of physiological strength. This directional migration is promoted by epidermal growth factor (EGF). To investigate how EGF and its receptor (EGFR) regulate this directionality, we first examined the effect of protein tyrosine kinase inhibitors, including PD158780, a specific inhibitor for EGFR, on this response. At low concentrations, PD158780 inhibited
Biophysical Journal, 2014
Biophysical Journal, 2014
Biophysical Journal, 2014
Proceedings of the National Academy of Sciences of the United States of America, 1992
We propose that protein translocation across membranes is driven by biased random thermal motion.... more We propose that protein translocation across membranes is driven by biased random thermal motion. This "Brownian ratchet" mechanism depends on chemical asymmetries between the cis and trans sides of the membrane. Several mechanisms could contribute to rectifying the thermal motion of the protein, such as binding and dissociation of chaperonins to the translocating chain, chain coiling induced by pH and/or ionic gradients, glycosylation, and disulfide bond formation. This helps explain the robustness and promiscuity of these transport systems.
Communicative & integrative biology, 2009
The ornate and diverse patterns of seashells testify to the complexity of living systems. Provoca... more The ornate and diverse patterns of seashells testify to the complexity of living systems. Provocative computational explorations have shown that similarly complex patterns may arise from the collective interaction of a small number of rules. This suggests that, although a system may appear complex, it may still be understood in terms of simple principles. It is still debatable whether shell patterns emerge from some undiscovered simple principles, or are the consequence of an irreducibly complex interaction of many effects. Recent work by Boettiger, Ermentrout and Oster on the biological mechanisms of shell patterning has provided compelling evidence that, at least for this system, simplicity produces diversity and complexity.
Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics, 2000
The elastic interaction of membrane inclusions provides one of the simplest physical realizations... more The elastic interaction of membrane inclusions provides one of the simplest physical realizations of multibody forces. Here we show how the cross-sectional shape of the inclusion greatly changes the character of the interaction, and illustrates a pattern formation mechanism. The formalism provides a transparent framework for modeling bilayer-inclusion boundary effects on the multibody interaction.
Design, Synthesis, and Applications, 2004
ABSTRACT
Quarterly reviews of biophysics, 1973
... complex systems. We shall not deal to any great extent with linear graph theory since it is a... more ... complex systems. We shall not deal to any great extent with linear graph theory since it is adequately treated in the technical literature (Berge, 1962; Berge & Ghouila-Houri, 1965; Harary, 1969; Seshu & Reed, 1961). The example ...
The bacteriophage T7 helicase is a ring-shaped hexameric motor protein that unwinds double-strand... more The bacteriophage T7 helicase is a ring-shaped hexameric motor protein that unwinds double-stranded DNA during DNA replication and recombination. To accomplish this it couples energy from the nucleotide hydrolysis cycle to translocate along one of the DNA strands. Here, we combine computational biology with new biochemical measurements to infer the following properties of the T7 helicase: (1) all hexameric subunits are catalytic; (2) the mechanical movement along the DNA strand is driven by the binding transition of nucleotide into the catalytic site; (3) hydrolysis is coordinated between adjacent subunits that bind DNA; (4) the hydrolysis step changes the affinity of a subunit for DNA allowing passage of DNA from one subunit to the next. We construct a numerical optimization scheme to analyze transient and steady-state biochemical measurements to determine the rate constants for the hydrolysis cycle and determine the flux distribution through the reaction network. We find that, under physiological and experimental conditions, there is no dominant pathway; rather there is a distribution of pathways that varies with the ambient conditions. Our analysis methods provide a systematic procedure to study kinetic pathways of multi-subunit, multi-state cooperative enzymes.
Biophysical Journal, 2014
Myxococcus xanthus is a Gram-negative, soil-dwelling bacterium that glides on surfaces, reversing... more Myxococcus xanthus is a Gram-negative, soil-dwelling bacterium that glides on surfaces, reversing direction approximately once every 6 min. Motility in M. xanthus is governed by the Che-like Frz pathway and the Ras-like Mgl pathway, which together cause the cell to oscillate back and forth. Previously, Igoshin et al. (2004) suggested that the cellular oscillations are caused by cyclic changes in concentration of active Frz proteins that govern motility. In this study, we present a computational model that integrates both the Frz and Mgl pathways, and whose downstream components can be read as motor activity governing cellular reversals. This model faithfully reproduces wildtype and mutant behaviors by simulating individual protein knockouts. In addition, the model can be used to examine the impact of contact stimuli on cellular reversals. The basic model construction relies on the presence of two nested feedback circuits, which prompted us to reexamine the behavior of M. xanthus cells. We performed experiments to test the model, and this cell analysis challenges previous assumptions of 30 to 60 min reversal periods in frzCD, frzF, frzE, and frzZ mutants. We demonstrate that this average reversal period is an artifact of the method employed to record reversal data, and that in the absence of signal from the Frz pathway, Mgl components can occasionally reverse the cell near wildtype periodicity, but frz- cells are otherwise in a long nonoscillating state.
Biophysical journal, Jan 1, 2005
Two theoretical formalisms are widely used in modeling mechanochemical systems such as protein mo... more Two theoretical formalisms are widely used in modeling mechanochemical systems such as protein motors: continuum Fokker-Planck models and discrete kinetic models. Both have advantages and disadvantages. Here we present a “finite volume” procedure to solve Fokker-Planck equations. The procedure relates the continuum equations to a discrete mechanochemical kinetic model while retaining many of the features of the continuum formulation. The resulting numerical algorithm is a generalization of the algorithm developed previously by Fricks, Wang, and Elston through relaxing the local linearization approximation of the potential functions, and a more accurate treatment of chemical transitions. The new algorithm dramatically reduces the number of numerical cells required for a prescribed accuracy. The kinetic models constructed in this fashion retain some features of the continuum potentials, so that the algorithm provides a systematic and consistent treatment of mechanical-chemical responses such as load-velocity relations, which are difficult to capture with a priori kinetic models. Several numerical examples are given to illustrate the performance of the method.
Proceedings of The National Academy of Sciences, 2001
Recent experiments have provided new quantitative measurements of the rippling phenomenon in fiel... more Recent experiments have provided new quantitative measurements of the rippling phenomenon in fields of developing myxobacteria cells. These measurements have enabled us to develop a mathematical model for the ripple phenomenon on the basis of the biochemistry of the C-signaling system, whereby individuals signal by direct cell contact. The model quantitatively reproduces all of the experimental observations and illustrates how
European Biophysics Journal With Biophysics Letters, 1996
Many cell movements appear to be driven by the polymerization of actin. Here we show how the forc... more Many cell movements appear to be driven by the polymerization of actin. Here we show how the force of polymerization can be generated by the thermal motions of the actin filaments near the sites of polymerization. We apply the model to explain the observations that the lamellipodial cytoskeleton is organized into an orthogonal network interspersed with filopodial protrusions, and that
... THE VELIGER © CMS, Inc., 1986 A Model for Shell Patterns Based on Neural Activity by BARD ERM... more ... THE VELIGER © CMS, Inc., 1986 A Model for Shell Patterns Based on Neural Activity by BARD ERMENTROUT ... 28, No.4 a b c Figure 1 Three fundamental classes of shell pigment markings on Bankivia fasciata: a, longitudinal bands; b, incremental lines; c, oblique stripes. ...
Trends in cell biology, 2003
Three protein motors have been unambiguously identified as rotary engines: the bacterial flagella... more Three protein motors have been unambiguously identified as rotary engines: the bacterial flagellar motor and the two motors that constitute ATP synthase (F(0)F(1) ATPase). Of these, the bacterial flagellar motor and F(0) motors derive their energy from a transmembrane ion-motive force, whereas the F(1) motor is driven by ATP hydrolysis. Here, we review the current understanding of how these protein motors convert their energy supply into a rotary torque.
Experimental and Theoretical Advances in Biological Pattern Formation, 1993
Institute for Nonlinear Science, 1996
Using molecular dynamics, we study the unbinding of ATP in F 1 -ATPase from its tight binding sta... more Using molecular dynamics, we study the unbinding of ATP in F 1 -ATPase from its tight binding state to its weak binding state. The calculations are made feasible through use of interpolated atomic structures from Wang and Oster [Nature 1998, 396: 279-282]. These structures are applied to atoms distant from the catalytic site. The forces from these distant atoms gradually drive a large primary region through a series of sixteen equilibrated steps that trace the hinge bending conformational change in the b-subunit that drives rotation of g-subunit. As the rotation progresses, we find a sequential weakening and breaking of the hydrogen bonds between the ATP molecule and the a-and b-subunits of the ATPase. This finding agrees with the ''binding-zipper'' model Wang, Biochim. Biophys. Acta 2000, 1458: 482-510.] In this model, the progressive formation of the hydrogen bonds is the energy source driving the rotation of the g-shaft during hydrolysis. Conversely, the corresponding sequential breaking of these bonds is driven by rotation of the shaft during ATP synthesis. Our results for the energetics during rotation suggest that the nucleotide's coordination with Mg 21 during binding and release is necessary to account for the observed high efficiency of the motor.
Human keratinocytes migrate towards the negative pole in DC electric fields of physiological stre... more Human keratinocytes migrate towards the negative pole in DC electric fields of physiological strength. This directional migration is promoted by epidermal growth factor (EGF). To investigate how EGF and its receptor (EGFR) regulate this directionality, we first examined the effect of protein tyrosine kinase inhibitors, including PD158780, a specific inhibitor for EGFR, on this response. At low concentrations, PD158780 inhibited
Biophysical Journal, 2014
Biophysical Journal, 2014
Biophysical Journal, 2014
Proceedings of the National Academy of Sciences of the United States of America, 1992
We propose that protein translocation across membranes is driven by biased random thermal motion.... more We propose that protein translocation across membranes is driven by biased random thermal motion. This "Brownian ratchet" mechanism depends on chemical asymmetries between the cis and trans sides of the membrane. Several mechanisms could contribute to rectifying the thermal motion of the protein, such as binding and dissociation of chaperonins to the translocating chain, chain coiling induced by pH and/or ionic gradients, glycosylation, and disulfide bond formation. This helps explain the robustness and promiscuity of these transport systems.
Communicative & integrative biology, 2009
The ornate and diverse patterns of seashells testify to the complexity of living systems. Provoca... more The ornate and diverse patterns of seashells testify to the complexity of living systems. Provocative computational explorations have shown that similarly complex patterns may arise from the collective interaction of a small number of rules. This suggests that, although a system may appear complex, it may still be understood in terms of simple principles. It is still debatable whether shell patterns emerge from some undiscovered simple principles, or are the consequence of an irreducibly complex interaction of many effects. Recent work by Boettiger, Ermentrout and Oster on the biological mechanisms of shell patterning has provided compelling evidence that, at least for this system, simplicity produces diversity and complexity.
Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics, 2000
The elastic interaction of membrane inclusions provides one of the simplest physical realizations... more The elastic interaction of membrane inclusions provides one of the simplest physical realizations of multibody forces. Here we show how the cross-sectional shape of the inclusion greatly changes the character of the interaction, and illustrates a pattern formation mechanism. The formalism provides a transparent framework for modeling bilayer-inclusion boundary effects on the multibody interaction.
Design, Synthesis, and Applications, 2004
ABSTRACT
Quarterly reviews of biophysics, 1973
... complex systems. We shall not deal to any great extent with linear graph theory since it is a... more ... complex systems. We shall not deal to any great extent with linear graph theory since it is adequately treated in the technical literature (Berge, 1962; Berge & Ghouila-Houri, 1965; Harary, 1969; Seshu & Reed, 1961). The example ...
The bacteriophage T7 helicase is a ring-shaped hexameric motor protein that unwinds double-strand... more The bacteriophage T7 helicase is a ring-shaped hexameric motor protein that unwinds double-stranded DNA during DNA replication and recombination. To accomplish this it couples energy from the nucleotide hydrolysis cycle to translocate along one of the DNA strands. Here, we combine computational biology with new biochemical measurements to infer the following properties of the T7 helicase: (1) all hexameric subunits are catalytic; (2) the mechanical movement along the DNA strand is driven by the binding transition of nucleotide into the catalytic site; (3) hydrolysis is coordinated between adjacent subunits that bind DNA; (4) the hydrolysis step changes the affinity of a subunit for DNA allowing passage of DNA from one subunit to the next. We construct a numerical optimization scheme to analyze transient and steady-state biochemical measurements to determine the rate constants for the hydrolysis cycle and determine the flux distribution through the reaction network. We find that, under physiological and experimental conditions, there is no dominant pathway; rather there is a distribution of pathways that varies with the ambient conditions. Our analysis methods provide a systematic procedure to study kinetic pathways of multi-subunit, multi-state cooperative enzymes.
Biophysical Journal, 2014
Myxococcus xanthus is a Gram-negative, soil-dwelling bacterium that glides on surfaces, reversing... more Myxococcus xanthus is a Gram-negative, soil-dwelling bacterium that glides on surfaces, reversing direction approximately once every 6 min. Motility in M. xanthus is governed by the Che-like Frz pathway and the Ras-like Mgl pathway, which together cause the cell to oscillate back and forth. Previously, Igoshin et al. (2004) suggested that the cellular oscillations are caused by cyclic changes in concentration of active Frz proteins that govern motility. In this study, we present a computational model that integrates both the Frz and Mgl pathways, and whose downstream components can be read as motor activity governing cellular reversals. This model faithfully reproduces wildtype and mutant behaviors by simulating individual protein knockouts. In addition, the model can be used to examine the impact of contact stimuli on cellular reversals. The basic model construction relies on the presence of two nested feedback circuits, which prompted us to reexamine the behavior of M. xanthus cells. We performed experiments to test the model, and this cell analysis challenges previous assumptions of 30 to 60 min reversal periods in frzCD, frzF, frzE, and frzZ mutants. We demonstrate that this average reversal period is an artifact of the method employed to record reversal data, and that in the absence of signal from the Frz pathway, Mgl components can occasionally reverse the cell near wildtype periodicity, but frz- cells are otherwise in a long nonoscillating state.