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Biomedical subjects

George Oster

Publications and source records attributed to George Oster.

34 records · Page 2Linked to original sources
PubMed2004

The junctional pore complex and the propulsion of bacterial cells.

Gliding motility is defined as translocation in the direction of the long axis of the bacterium while in contact with a surface. This definition leaves unspecified any mechanism and, indeed, it appears that there is more than one physiological system underlying the same type of motion. Currently, two distinct mechanisms have been discovered in myxobacteria. One requires the extension, attachment, and retraction of type IV pili to pull the cell forwards. Recent experimental evidence suggests that a second mechanism for gliding motility involves the extrusion of slime from an organelle called the 'junctional pore complex'. This review discusses the role of slime extrusion and the junctional pore complex in the gliding motility of both cyanobacteria and myxobacteria.

Cyanobacteria↗
PubMed2004

Torque generation by the Fo motor of the sodium ATPase.

Based on recent structural and functional findings, we have constructed a mathematical model for the sodium-driven Fo motor of the F1Fo-ATPase from the anaerobic bacterium Propionigenium modestum. The model reveals the mechanochemical principles underlying the Fo motor's operation, and explains all of the existing experimental data on wild-type and mutant Fo motors. In particular, the model predicts a nonmonotonic dependence of the ATP hydrolysis activity on the sodium concentration, a prediction confirmed by new experiments. To explain experimental observations, the positively charged stator residue (R227) must assume different positions in the ATP synthesis and hydrolysis directions. This work also illustrates how to extract a motor mechanism from dynamical experimental observations in the absence of complete structural information.

Adenosine Triphosphate↗
PubMed2003

The hydration dynamics of polyelectrolyte gels with applications to cell motility and drug delivery.

We combine the physics of gels with the hydrodynamics of two-phase fluids to construct a set of equations that describe the hydration dynamics of polyelectrolyte gels. We use the model to address three problems. First, we express the effective diffusion constants for neutral and charged spherically distributed gels in terms of microscopic parameters. Second, we use the model to describe the locomotion of nematode sperm cells. Finally, we describe the swelling dynamics of polyelectrolyte gels used for drug release.

Animals↗
PubMed2003

Polymer motors: pushing out the front and pulling up the back.

Mechanical work in cells is performed by specialized motor proteins that operate in a continuous mechanochemical cycle. Less complex, but still efficient, 'one-shot' motors evolved based on the assembly and disassembly of polymers. We review the mechanisms of pushing and pulling by actin and microtubule filaments and the organizational principles of actin networks. We show how these polymer force generators are used for the propulsion of intracellular pathogens, protrusion of lamellipodia and mitotic movements. We discuss several examples of cellular forces generated by the assembly and disassembly of polymer gels.

Actins↗
PubMed2003

Elastic energy storage in beta-sheets with application to F1-ATPase.

We present a methodology for obtaining the elastic properties of protein motifs. We combine the use of interpolated structures (IS), molecular dynamics (MD) and collective coordinates to deduce the elastic properties of the beta-sheet in F(1) ATPase. We find that about 3.5 kcal/mol (6 k(B) T at room temperature) of elastic energy is stored in the beta-sheet as the beta-subunit undergoes its hinge bending motion, in good agreement with the finite element model of Wang and Oster [Nature (1998) 396:279-282]. The technique should be useful for beta-sheets in other proteins and aid in the construction of phenomenological models for molecular motors that are computationally prohibitive for MD alone.

Kinetics↗
PubMed2003

The conformational states of Mg.ATP in water.

The conformational equilibria of Mg.ATP in solution is studied using molecular dynamics (MD) augmented with umbrella sampling methods. Free energy comparisons show that the Mg(2+) ion is equally likely to coordinate the oxygens of the two end phosphates, or of all three phosphates. The MD trajectories reveal two major degrees of freedom of the Mg.ATP molecule in solution, and we compute the free energy as a function of these variables, and determine its elastic properties. Comparing the free energy function with several crystallographic structures of ATP analogs, we find that the crystal structures correspond to states where ATP would be elastically strained. The average water density around Mg.ATP is investigated to show the average number of hydrogen bonds and the hydrophobicity.

Adenosine Triphosphate↗
PubMed2003

The unbinding of ATP from F1-ATPase.

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 beta-subunit that drives rotation of gamma-subunit. As the rotation progresses, we find a sequential weakening and breaking of the hydrogen bonds between the ATP molecule and the alpha- and beta-subunits of the ATPase. This finding agrees with the "binding-zipper" model [Oster and 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 gamma-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(2+) during binding and release is necessary to account for the observed high efficiency of the motor.

Adenosine Triphosphate↗
PubMed2003

The motility of mollicutes.

Recent experiments show that the conformation of filament proteins play a role in the motility and morphology of many different types of bacteria. Conformational changes in the protein subunits may produce forces to drive propulsion and cell division. Here we present a molecular mechanism by which these forces can drive cell motion. Coupling of a biochemical cycle, such as ATP hydrolysis, to the dynamics of elastic filaments enable elastic filaments to propagate deformations that generate propulsive forces. We demonstrate this possibility for two classes of wall-less bacteria called mollicutes: the swimming of helical-shaped Spiroplasma, and the gliding motility of Mycoplasma.

Bacterial Physiological Phenomena↗
PubMed2003

Protein interactions and membrane geometry.

The difficulty in growing crystals for x-ray diffraction analysis has hindered the determination of membrane protein structures. However, this is changing with the advent of a new method for growing high quality membrane protein crystals from the lipidic cubic phase. Although successful, the mechanism underlying this method has remained unclear. Here, we present a theoretical analysis of the process. We show that it is energetically favorable for proteins embedded in the highly curved cubic phase to cluster together in flattened regions of the membrane. This stabilizes the lamellar phase, permitting its outgrowth from the cubic phase. A kinetic barrier-crossing model is developed to determine the free energy barrier to crystallization from the time-dependent growth of protein clusters. Determining the values of key parameters provides both a rational basis for optimizing the experimental procedure for membrane proteins that have not yet been crystallized and insight into the analogous cubic to lamellar transitions in cells. We also discuss the implications of this mechanism for protein sorting at the exit sites of the Golgi and endoplasmic reticulum and the general stabilization of membrane structures.

Computer Simulation↗
PubMed2003

Force generation by actin polymerization II: the elastic ratchet and tethered filaments.

The motion of many intracellular pathogens is driven by the polymerization of actin filaments. The propulsive force developed by the polymerization process is thought to arise from the thermal motions of the polymerizing filament tips. Recent experiments suggest that the nucleation of actin filaments involves a phase when the filaments are attached to the pathogen surface by a protein complex. Here we extend the "elastic ratchet model" of Mogilner and Oster to incorporate these new findings. We apply this "tethered ratchet" model to derive the force-velocity relation for Listeria and discuss relations of our theoretical predictions to experimental measurements. We also discuss "symmetry breaking" dynamics observed in ActA-coated bead experiments, and the implications of the model for lamellipodial protrusion in migrating cells.

Actins↗
PubMed2003

Rotary protein motors.

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.

Adenosine Triphosphate↗
PubMed2002

How myxobacteria glide.

BACKGROUND: Many microorganisms, including myxobacteria, cyanobacteria, and flexibacteria, move by gliding. Although gliding always describes a slow surface-associated translocation in the direction of the cell's long axis, it can result from two very different propulsion mechanisms: social (S) motility and adventurous (A) motility. The force for S motility is generated by retraction of type 4 pili. A motility may be associated with the extrusion of slime, but evidence has been lacking, and how force might be generated has remained an enigma. Recently, nozzle-like structures were discovered in cyanobacteria from which slime emanated at the same rate at which the bacteria moved. This strongly implicates slime extrusion as a propulsion mechanism for gliding. RESULTS: Here we show that similar but smaller nozzle-like structures are found in Myxococcus xanthus and that they are clustered at both cell poles, where one might expect propulsive organelles. Furthermore, light and electron microscopical observations show that slime is secreted in ribbons from the ends of cells. To test whether the slime propulsion hypothesis is physically reasonable, we construct a mathematical model of the slime nozzle to see if it can generate a force sufficient to propel M. xanthus at the observed velocities. The model assumes that the hydration of slime, a cationic polyelectrolyte, is the force-generating mechanism. CONCLUSIONS: The discovery of nozzle-like organelles in various gliding bacteria suggests their role in prokaryotic gliding. Our calculations and our observations of slime trails demonstrate that slime extrusion from such nozzles can account for most of the observed properties of A motile gliding.

Cyanobacteria↗
PubMed2002

How nematode sperm crawl.

Sperm of the nematode, Ascaris suum, crawl using lamellipodial protrusion, adhesion and retraction, a process analogous to the amoeboid motility of other eukaryotic cells. However, rather than employing an actin cytoskeleton to generate locomotion, nematode sperm use the major sperm protein (MSP). Moreover, nematode sperm lack detectable molecular motors or the battery of actin-binding proteins that characterize actin-based motility. The Ascaris system provides a simple 'stripped down' version of a crawling cell in which to examine the basic mechanism of cell locomotion independently of other cellular functions that involve the cytoskeleton. Here we present a mechanochemical analysis of crawling in Ascaris sperm. We construct a finite element model wherein (a) localized filament polymerization and bundling generate the force for lamellipodial extension and (b) energy stored in the gel formed from the filament bundles at the leading edge is subsequently used to produce the contraction that pulls the rear of the cell forward. The model reproduces the major features of crawling sperm and provides a framework in which amoeboid cell motility can be analyzed. Although the model refers primarily to the locomotion of nematode sperm, it has important implications for the mechanics of actin-based cell motility.

Animals↗
PubMedDate not supplied

Rippling of myxobacteria.

Myxobacteria colonies during their aggregation phase propagate complex waves over their surface. These waves are fundamentally different from the analogous phenomenon in diffusion-reaction systems or in populations of Dictyostelium discoideum where colliding waves annhilate. Myxobacterial waves appear to pass through one another, analogous to solitons. Moreover, individual bacteria oscillate back and forth, exhibiting no net mass transfer. A mathematical model can explain virtually all of the experimentally observed properties of these waves and draw several conclusions about the properties of the intercelular signaling system.

Cell Movement↗