Biomedical subjects

F Jülicher

Publications and source records attributed to F Jülicher.

At least 19 recordsLinked to original sources

PubMed2006

Dynamics and mechanics of motor-filament systems.

Motivated by the cytoskeleton of eukaryotic cells, we develop a general framework for describing the large-scale dynamics of an active filament network. In the cytoskeleton, active cross-links are formed by motor proteins that are able to induce relative motion between filaments. Starting from pair-wise interactions of filaments via such active processes, our framework is based on momentum conservation and an analysis of the momentum flux. This allows us to calculate the stresses in the filament network generated by the action of motor proteins. We derive effective theories for the filament dynamics which can be related to continuum theories of active polar gels. As an example, we discuss the stability of homogenous isotropic filament distributions in two spatial dimensions.

Biomechanical Phenomena↗

PubMed2006

Contractility and retrograde flow in lamellipodium motion.

We present a phenomenological description of cell locomotion on a solid substrate. The material properties of the actin cytoskeleton in the lamellipodium are described by the constitutive equations of a viscous polar gel with intrinsic activity. The polymerization of the gel takes place in a localized region near the leading edge. Using a simple two-dimensional description, we calculate in the steady state the thickness profile of the lamellipodium which at the rear connects to the cell body; we also calculate the flow profiles and the forces exerted on the substrate. The cell velocity is estimated as a function of externally applied forces. Our description is consistent with experimentally observed properties of motile cells such as the existence of a retrograde flow in the lamellipodium and a dipolar force distribution exerted by the cell on the substrate.

Actins↗

PubMed2005

Generic theory of active polar gels: a paradigm for cytoskeletal dynamics.

We develop a general theory for active viscoelastic materials made of polar filaments. This theory is motivated by the dynamics of the cytoskeleton. The continuous consumption of a fuel leads to a non equilibrium state characterized by the generation of flows and stresses. Our theory can be applied to experiments in which cytoskeletal patterns are set in motion by active processes such as those which are at work in cells.

Cell Physiological Phenomena↗

PubMed2005

Robust formation of morphogen gradients.

We discuss the formation of graded morphogen profiles in a cell layer by nonlinear transport phenomena, important for patterning developing organisms. We focus on a process termed transcytosis, where morphogen transport results from the binding of ligands to receptors on the cell surface, incorporation into the cell, and subsequent externalization. Starting from a microscopic model, we derive effective transport equations. We show that, in contrast to morphogen transport by extracellular diffusion, transcytosis leads to robust ligand profiles which are insensitive to the rate of ligand production.

Cell Communication↗

PubMed2004

Asters, vortices, and rotating spirals in active gels of polar filaments.

We develop a general theory for active viscoelastic materials made of polar filaments. This theory is motivated by the dynamics of the cytoskeleton. The continuous consumption of a fuel generates a nonequilibrium state characterized by the generation of flows and stresses. Our theory applies to any polar system with internal energy consumption such as active chemical gels and cytoskeletal networks which are set in motion by active processes at work in cells.

Adenosine Triphosphate↗

PubMed2004

Role of tensile stress in actin gels and a symmetry-breaking instability.

It has been observed experimentally that the actin gel grown from spherical beads coated with polymerization enzymes spontaneously breaks the symmetry of its spherical shape, and yields a "comet" pushing the bead forward. We propose a mechano-chemical coupling mechanism for the initialization of this symmetry breaking. Key assumptions are that the dissociation of the gel takes place mostly in the region of the external surface, and that the rates of the dissociation depend on the tensile stress in the gel. We analyze a simplified two-dimensional model with a circular substrate. Our analysis shows that the symmetric steady state is always unstable against the inhomogeneous modulation of the thickness of the gel layer, for any radius of the circular substrate. We argue that this model represents the essential feature of three-dimensional systems for a certain range of characteristic lengths of the modulation. The characteristic time of the symmetry-breaking process in our model depends linearly on the radius of curvature of the substrate surface, which is consistent with experimental results, using spherical latex beads as substrate. Our analysis of the symmetry-breaking phenomenon demonstrates aspects of mechano-chemical couplings that should be working in vivo as well as in vitro.

Actins↗

PubMed2004

Membranes with rotating motors: microvortex assemblies.

We study collections of rotatory motors confined to 2-dimensional manifolds. The rotational motion induces a repulsive hydrodynamic interaction between motors leading to a non-trivial collective behavior. For high rotation speed, motors should arrange on a triangular lattice exhibiting crystalline order. At low speed, they form a disordered phase where diffusion is enhanced by velocity fluctuations. In confining geometries and under suitable boundary conditions, motor-generated flow might enhance left-right symmetry-breaking transport. All these effects should be experimentally observable for motors driven by external fields and for dipolar biological motors embedded into lipid membranes in a viscoelastic solvent.

Adenosine Triphosphatases↗

PubMed2004

Fluid membranes exchanging material with external reservoirs.

We investigate the dynamics of a single component fluid bilayer, which exchanges material with the surrounding fluid. We derive covariant equations of motion taking into account solvent permeation, exchange of lipids between solvent and the membrane and discuss the sources of noise in these equations. Different lipid concentrations on both sides of the membrane lead to a non-equilibrium state. We discuss steady states as well as shape instabilities which occur at a critical osmotic-pressure difference.

Biophysics↗

PubMed2002

Bidirectional cooperative motion of molecular motors.

Recently, in a beautiful set of experiments, it has been shown that a Ncd mutant, NK11, which lacks directionality in its individual motion, was able to exhibit a new kind of directed motion in motility assays (Endow, S. A. & Higuchi, H. (2000) Nature (London) 406, 913-916): the filaments keep a given velocity for a while and then suddenly move in the opposite direction with similar velocity. We show that these observations nicely illustrate the concept of dynamic transitions in motor collections introduced earlier in the case of an infinite number of motors. We investigate the experimentally relevant case of a finite number of motors both when directionality is present (kinesins, myosins, Ncd) and absent (NK11). Using a symmetric two-state model, we demonstrate that bidirectional motion is the signature of a dynamic transition that results from the collective behavior of many motors acting on the same filament. For motors exhibiting directional bias individually, an asymmetric two-state model is appropriate. In that case, dynamic transitions exist for motor collections in the presence of an external force. We give predictions for the dependence of motion on ATP concentration, external forces, and the number of motors involved. In particular, we show that the reversal time grows exponentially with the number of motors per filament.

Computer Simulation↗

PubMed2001

Comparison of a hair bundle's spontaneous oscillations with its response to mechanical stimulation reveals the underlying active process.

Hearing relies on active filtering to achieve exquisite sensitivity and sharp frequency selectivity. In a quiet environment, the ears of many vertebrates become unstable and emit one to several tones. These spontaneous otoacoustic emissions, the most striking manifestation of the inner ear's active process, must result from self-sustained mechanical oscillations of aural constituents. The mechanoreceptive hair bundles of hair cells in the bullfrog's sacculus have the ability to amplify mechanical stimuli and oscillate spontaneously. By comparing a hair bundle's spontaneous oscillations with its response to small mechanical stimuli, we demonstrate a breakdown in a general principle of equilibrium thermodynamics, the fluctuation-dissipation theorem. We thus confirm that a hair bundle's spontaneous movements are produced by energy-consuming elements within the hair cell. To characterize the dynamical behavior of the active process, we introduce an effective temperature that, for each frequency component, quantifies a hair bundle's deviation from thermal equilibrium. The effective temperature diverges near the bundle's frequency of spontaneous oscillation. This behavior, which is not generic for active oscillators, can be accommodated by a simple model that characterizes quantitatively the fluctuations of the spontaneous movements as well as the hair bundle's linear response function.

Animals↗

PubMed2001

Self-propagating patterns in active filament bundles.

Bundles of polar filaments which interact via active elements can exhibit complex dynamic behaviors. By using a simple and general description for the bundle dynamics, we find regimes for which density profiles propagate as solitary waves with a characteristic velocity along the bundle. These behaviors emerge from an interplay of local contractions in the bundle and relative sliding of oppositely oriented filaments. By introducing filament binding to and detachment from a substrate, the system is able to generate net motion as a self-organization phenomenon.

Cell Movement↗

PubMed2001

Physical basis of two-tone interference in hearing.

The cochlea uses active amplification to capture faint sounds. It has been proposed that the amplifier comprises a set of self-tuned critical oscillators: each hair cell contains a force-generating dynamical system that is maintained at the threshold of an oscillatory instability, or Hopf bifurcation. While the active response to a pure tone provides frequency selectivity, exquisite sensitivity, and wide dynamic range, its intrinsic nonlinearity causes tones of different frequency to interfere with one another in the cochlea. Here we determine the response to two tones, which provides a framework for understanding how the ear processes the more complex sounds of speech and music. Our calculations of two-tone suppression and the spectrum of distortion products generated by a critical oscillator accord with experimental observations of basilar membrane motion and the nervous response. We discuss how the response of a set of self-tuned oscillators, covering a range of characteristic frequencies, represents the structure of a complex sound. The frequency components of the stimulus can be inferred from the timing of neural spikes elicited by the vibrating hair cells. Passive prefiltering by the basilar membrane improves pitch discrimination by reducing interference between tones. Our analysis provides a general framework for examining the relation between the physical nature of the peripheral detection apparatus and psychophysical phenomena such as the sensation of dissonance and auditory illusions.

Cochlea↗

PubMed2000

Actively contracting bundles of polar filaments.

We introduce a phenomenological model to study the properties of bundles of polar filaments which interact via active elements. The stability of the homogeneous state, the attractors of the dynamics in the unstable regime, and the tensile stress generated in the bundle are discussed. We find that the interaction of parallel filaments can induce unstable behavior and is responsible for active contraction and tension in the bundle. The interaction between antiparallel filaments leads to filament sorting. Our model could apply to simple contractile structures in cells such as stress fibers.

Actins↗

PubMed2000

Auditory sensitivity provided by self-tuned critical oscillations of hair cells.

We introduce the concept of self-tuned criticality as a general mechanism for signal detection in sensory systems. In the case of hearing, we argue that active amplification of faint sounds is provided by a dynamical system that is maintained at the threshold of an oscillatory instability. This concept can account for the exquisite sensitivity of the auditory system and its wide dynamic range as well as its capacity to respond selectively to different frequencies. A specific model of sound detection by the hair cells of the inner ear is discussed. We show that a collection of motor proteins within a hair bundle can generate oscillations at a frequency that depends on the elastic properties of the bundle. Simple variation of bundle geometry gives rise to hair cells with characteristic frequencies that span the range of audibility. Tension-gated transduction channels, which primarily serve to detect the motion of a hair bundle, also tune each cell by admitting ions that regulate the motor protein activity. By controlling the bundle's propensity to oscillate, this feedback automatically maintains the system in the operating regime where it is most sensitive to sinusoidal stimuli. The model explains how hair cells can detect sounds that carry less energy than the background noise.

Animals↗

PubMed1999

Energy transduction of isothermal ratchets: generic aspects and specific examples close to and far from equilibrium.

We study the energetics of isothermal ratchets which are driven by a chemical reaction between two states, and operate in contact with a single heat bath of constant temperature. We discuss generic aspects of energy transduction such as Onsager relations in the linear response regime as well as the efficiency and dissipation close to and far from equilibrium. In the linear response regime where the system operates reversibly, the efficiency is in general nonzero. Studying the properties for specific examples of energy landscapes and transitions, we observe in the linear response regime that the efficiency can have a maximum as a function of temperature. Far from equilibrium in the fully irreversible regime, we find a maximum of the efficiency with values larger than in the linear regime for an optimal choice of the chemical driving force. We show that the corresponding efficiencies can be of the order of 50%. A simple analytic argument allows us to estimate the efficiency in this irreversible regime for small external forces.

Energy Metabolism↗

PubMed1998

Acting on actin: the electric motility assay.

We have developed a novel technique which allows one to direct the two dimensional motion of actin filaments on a myosin coated sheet using a weak electric field parallel to the plane of motion. The filament velocity can be increased or decreased, and even reversed, as a function of orientation and strength of the field. PMMA (poly(methylmethacrylate)) gratings, which act as rails for actin, allow one for the first time to explore three quadrants of the force velocity diagram. We discuss effective friction, duty ratio and stall force at different myosin densities. A discontinuity in the velocity force relationship suggests the existence of dynamical phase transition.

Actins↗

PubMed1998

Motion of RNA polymerase along DNA: a stochastic model.

RNA polymerase is a key transcription enzyme that moves along a DNA double helix to polymerize an RNA transcript. Recent progress in micromechanical experiments permits quantitative studies of forces and motion generated by the enzyme. We present in this paper a chemical kinetics description of RNA polymerase motion. The model is based on a classical chemical kinetics description of polymerization reactions driven by a free energy gain that depends on forces applied externally at the catalytic site. The RNA polymerase controlled activation barrier of the reaction is assumed to be strongly dependent on inhibitory internal strains of the RNA polymerase molecule. The sequence sensitivity of RNA polymerase is described by a linear coupling between the height of the activation barrier and the local DNA sequence. Our model can simulate optical trap experiments and allows us to study the dynamics of chemically halted complexes that are important for footprinting studies. We find that the effective stall force is a sequence-dependent, statistical quantity, whose distribution depends on the observation time. The results are consistent with the experimental observations to date.

Base Sequence↗

PubMed1996

Quantitation of regional cerebral blood flow with 15O-butanol and positron emission tomography in humans.

We describe the implementation and validation of a combined dynamic-autoradiographic approach for measuring the regional cerebral blood flow (rCBF) with 15O-butanol. From arterial blood data sampled at a rate of 1 s and list mode data of the cerebral radioactivity accumulated over 100 s, the time shift between blood and tissue curves, the dispersion constant DC, the partition coefficient p, and the CBF were estimated by least squares fitting. Using the fit results, a pixel-by-pixel parametrization of rCBF was computed for a single 40-s (autoradiographic) 15O-butanol uptake image. The mean global CBF found in 27 healthy subjects was 49 +/- 8 ml 100 g-1 min-1. Gray and white matter rCBF were 83 +/- 20 and 16 +/- 3 ml 100 g-1 min-1, respectively, with a corresponding partition coefficient p of 0.77 +/- 0.18 and 0.77 +/- 0.29 ml/g in both compartments. The quantitative images resulted in a significantly higher gray matter rCBF than the autoradiographic images.

Adult↗