Biomedical subjects

Frank Jülicher

Publications and source records attributed to Frank Jülicher.

18 recordsLinked to original sources

PubMed2006

Spindle oscillations during asymmetric cell division require a threshold number of active cortical force generators.

BACKGROUND: Asymmetric division of the C. elegans zygote is due to the posterior-directed movement of the mitotic spindle during metaphase and anaphase. During this movement along the anterior-posterior axis, the spindle oscillates transversely. These motions are thought to be driven by a force-generating complex-possibly containing the motor protein cytoplasmic dynein-that is located at the cell cortex and pulls on microtubules growing out from the spindle poles. A theoretical analysis indicates that the oscillations might arise from mechanical coordination of the force-generating motors, and this coordination is mediated by the load dependence of the motors' detachment from the microtubules. The model predicts that the motor activity must exceed a threshold for oscillations to occur. RESULTS: We have tested the existence of a threshold by using RNA interference to gradually reduce the levels of dynein light intermediate chain as well as GPR-1 and GPR-2 that are involved in the G protein-mediated regulation of the force generators. We found an abrupt cessation of oscillations as expected if the motor activity dropped below a threshold. Furthermore, we can account for the complex choreography of the mitotic spindle-the precise temporal coordination of the buildup and die-down of the transverse oscillations with the posterior displacement-by a gradual increase in the processivity of a single type of motor machinery during metaphase and anaphase. CONCLUSIONS: The agreement between our results and modeling suggests that the force generators themselves have the intrinsic capability of generating oscillations when opposing forces exceed a threshold.

Anaphase↗

PubMed2006

Postsynaptic mad signaling at the Drosophila neuromuscular junction.

BACKGROUND: Cell-to-cell communication at the synapse involves synaptic transmission as well as signaling mediated by growth factors, which provide developmental and plasticity cues. There is evidence that a retrograde, presynaptic transforming growth factor-beta (TGF-beta) signaling event regulates synapse development and function in Drosophila. RESULTS: Here we show that a postsynaptic TGF-beta signaling event occurs during larval development. The type I receptor Thick veins (Tkv) and the R-Smad transcription factor Mothers-against-dpp (Mad) are localized postsynaptically in the muscle. Furthermore, Mad phosphorylation occurs in regions facing the presynaptic active zones of neurotransmitter release within the postsynaptic subsynaptic reticulum (SSR). In order to monitor in real time the levels of TGF-beta signaling in the synapse during synaptic transmission, we have established a FRAP assay to measure Mad nuclear import/export in the muscle. We show that Mad nuclear trafficking depends on stimulation of the muscle. CONCLUSIONS: Our data suggest a mechanism linking synaptic transmission and postsynaptic TGF-beta signaling that may coordinate nerve-muscle development and function.

Active Transport, Cell Nucleus↗

PubMed2006

Hydrodynamic flow patterns and synchronization of beating cilia.

We calculate the hydrodynamic flow field generated far from a cilium which is attached to a surface and beats periodically. In the case of two beating cilia, hydrodynamic interactions can lead to synchronization of the cilia, which are nonlinear oscillators. We present a state diagram where synchronized states occur as a function of the distance of cilia and the relative orientation of their beat. Synchronized states occur with different relative phases. In addition, asynchronous solutions exist. Our work could be relevant for the synchronized motion of cilia generating hydrodynamic flows on the surface of cells.

Animals↗

PubMed2005

Continuum description of the cytoskeleton: ring formation in the cell cortex.

Motivated by the formation of ringlike filament structures in the cortex of plant and animal cells, we study the dynamics of a two-dimensional layer of cytoskeletal filaments and motor proteins near a surface by a general continuum theory. As a result of active processes, dynamic patterns of filament orientation and density emerge via instabilities. We show that self-organization phenomena can lead to the formation of stationary and oscillating rings. We present state diagrams that reveal a rich scenario of asymptotic behaviors and discuss the role of boundary conditions.

Biological Clocks↗

PubMed2005

Universal critical behavior of noisy coupled oscillators: a renormalization group study.

We show that the synchronization transition of a large number of noisy coupled oscillators is an example for a dynamic critical point far from thermodynamic equilibrium. The universal behaviors of such critical oscillators, arranged on a lattice in a d -dimensional space and coupled by nearest-neighbors interactions, can be studied using field-theoretical methods. The field theory associated with the critical point of a homogeneous oscillatory instability (or Hopf bifurcation of coupled oscillators) is the complex Ginzburg-Landau equation with additive noise. We perform a perturbative renormalization group (RG) study in a (4-epsilon)-dimensional space. We develop an RG scheme that eliminates the phase and frequency of the oscillations using a scale-dependent oscillating reference frame. Within Callan-Symanzik's RG scheme to two-loop order in perturbation theory, we find that the RG fixed point is formally related to the one of the model A dynamics of the real Ginzburg-Landau theory with an O2 symmetry of the order parameter. Therefore, the dominant critical exponents for coupled oscillators are the same as for this equilibrium field theory. This formal connection with an equilibrium critical point imposes a relation between the correlation and response functions of coupled oscillators in the critical regime. Since the system operates far from thermodynamic equilibrium, a strong violation of the fluctuation-dissipation relation occurs and is characterized by a universal divergence of an effective temperature. The formal relation between critical oscillators and equilibrium critical points suggests that long-range phase order exists in critical oscillators above two dimensions.

Journal Article↗

PubMed2005

Theory of mitotic spindle oscillations.

During unequal cell division the mitotic spindle is positioned away from the center of the cell before cell cleavage. In many biological systems this repositioning is accompanied by oscillatory movements of the spindle. We present a theoretical description for mitotic spindle oscillations. We show that the cooperative attachment and detachment of cortical force generators to astral microtubules leads to spontaneous oscillations beyond a critical number of force generators. This mechanism can quantitatively describe the spindle oscillations observed during unequal division of the one cell stage Caenorhabditis elegans embryo.

Animals↗

PubMed2005

Filament depolymerization by motor molecules.

Motor proteins that specifically interact with the ends of cytoskeletal filaments can induce filament depolymerization. A phenomenological description of this process is presented. We show that under certain conditions motors dynamically accumulate at the filament ends. We compare simulations of two microscopic models to the phenomenological description. The depolymerization rate can exhibit maxima and dynamic instabilities as a function of the bulk motor density for processive depolymerization. We discuss our results in relation to experimental studies of Kin-13 family motor proteins.

Models, Biological↗

PubMed2005

Opening of nucleic-acid double strands by helicases: active versus passive opening.

Helicase proteins move along double-stranded nucleic-acid molecules and unwind the double helix. This paper presents a theoretical study of the coupling between helicase translocation and duplex unwinding. Two different cases-active and passive opening-are usually distinguished. In active opening, the helicase directly destabilizes the double-stranded nucleic acid (dsNA) to promote opening. Passive opening implies that the helicase binds ssNA available when a thermal fluctuation partially opens the dsNA. We formulate a discrete model for helicase motion. An interaction potential describes how the helicase affects duplex unwinding when near a junction between single-stranded and double-stranded NA. Different choices of the potential correspond to the cases of active and passive opening. An optimal choice of interaction potential leads to a helicase which can unwind NA as rapidly as it translocates on single strands.

Binding Sites↗

PubMed2005

Oscillations in cell biology.

Oscillations play an important role in many dynamic cellular processes. They can emerge as the collective dynamic behavior of an ensemble of interacting components in the cell. Examples include oscillations in cytoskeletal structures such as the axonemes of cilia. Spontaneous oscillations of mechano-sensitive hair bundles have been shown to give frequency selectivity and amplification to mechano-sensation. In some bacteria, oscillations of Min proteins are important for division site selection. Genetic oscillators form the basis of circadian clocks. All these oscillations share many general features. Models and theoretical approaches are essential for an understanding of the principles underlying these dynamic cellular processes.

Animals↗

PubMed2004

Universal critical behavior of noisy coupled oscillators.

We study the universal thermodynamic properties of systems consisting of many coupled oscillators operating in the vicinity of a homogeneous oscillating instability. In the thermodynamic limit, the Hopf bifurcation is a dynamic critical point far from equilibrium described by a statistical field theory. We perform a perturbative renormalization group study, and show that at the critical point a generic relation between correlation and response functions appears. At the same time, the fluctuation-dissipation relation is strongly violated.

Journal Article↗

PubMed2004

Active hair-bundle motility harnesses noise to operate near an optimum of mechanosensitivity.

The ear relies on nonlinear amplification to enhance its sensitivity and frequency selectivity to oscillatory mechanical stimuli. It has been suggested that this active process results from the operation of dynamical systems that operate in the vicinity of an oscillatory instability, a Hopf bifurcation. In the bullfrog's sacculus, a hair cell can display spontaneous oscillations of its mechanosensory hair bundle. The behavior of an oscillatory hair bundle resembles that of a critical oscillator. We present here a theoretical description of the effects of intrinsic noise on active hair-bundle motility. An oscillatory instability can result from the interplay between a region of negative stiffness in the bundle's force-displacement relation and the Ca(2+)-regulated activity of molecular motors. We calculate a state diagram that describes the possible dynamical states of the hair bundle in the absence of fluctuations. Taking into account thermal fluctuations, the stochastic nature of transduction channels' gating, and of the forces generated by molecular motors, we discuss conditions that yield a response function and spontaneous noisy movements of the hair bundle in quantitative agreement with previously published experiments. We find that the magnitude of the fluctuations resulting from the active processes that mediate mechanical amplification remains just below that of thermal fluctuations. Fluctuations destroy the phase coherence of spontaneous oscillations and restrict the bundle's sensitivity as well as frequency selectivity to small oscillatory stimuli. We show, however, that a hair bundle studied experimentally operates near an optimum of mechanosensitivity in our state diagram.

Acoustic Stimulation↗

PubMed2004

Dpp gradient formation by dynamin-dependent endocytosis: receptor trafficking and the diffusion model.

Developing cells acquire positional information by reading the graded distribution of morphogens. In Drosophila, the Dpp morphogen forms a long-range concentration gradient by spreading from a restricted source in the developing wing. It has been assumed that Dpp spreads by extracellular diffusion. Under this assumption, the main role of endocytosis in gradient formation is to downregulate receptors at the cell surface. These surface receptors bind to the ligand and thereby interfere with its long-range movement. Recent experiments indicate that Dpp spreading is mediated by Dynamin-dependent endocytosis in the target tissue, suggesting that extracellular diffusion alone cannot account for Dpp dispersal. Here, we perform a theoretical study of a model for morphogen spreading based on extracellular diffusion, which takes into account receptor binding and trafficking. We compare profiles of ligand and surface receptors obtained in this model with experimental data. To this end, we monitored directly the pool of surface receptors and extracellular Dpp with specific antibodies. We conclude that current models considering pure extracellular diffusion cannot explain the observed role of endocytosis during Dpp long-range movement.

Amino Acid Sequence↗

PubMed2003

A motor that makes its own track: helicase unwinding of DNA.

We study the unwinding of DNA by helicase proteins as a representative system in which a motor protein interacts with a mobile obstacle. In our discrete model, the interaction between the helicase and the DNA fork is characterized by an interaction potential. For the case of a hard-wall potential, the helicase opens the DNA by rectifying thermal fluctuations which spontaneously open base pairs. A potential with nonzero range describes the destabilization of the double strand by the enzymatic action of the helicase. We derive solutions for the opening speed as a function of the potential shape and relate our results to experiments on helicase motion.

DNA↗

PubMed2003

Membranes with rotating motors.

We study collections of rotatory motors confined to two-dimensional manifolds. These systems show a nontrivial collective behavior since the rotational motion leads to a repulsive hydrodynamic interaction between motors. While for high rotation speed motors might exhibit crystalline order, they form at low speed a disordered phase where diffusion is enhanced by velocity fluctuations. 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↗

PubMed2003

Self-organization and mechanical properties of active filament bundles.

A general framework for the description of active bundles of polar filaments is presented. The activity of the bundle results from mobile cross-links that induce relative displacements between the aligned filaments. Our generic description is based on momentum conservation within the bundle. By specifying the internal forces, a simple minimal model for the bundle dynamics can be derived, capturing a rich variety of dynamic behaviors. In particular, contracted states as well as solitary and oscillatory waves appear through dynamic instabilities. We present the full bifurcation diagram of this model and study the effects of a dynamic motor distribution on the bundle dynamics. Furthermore, we discuss the mechanical properties of the bundle in the presence of externally applied forces. Our description is motivated by dynamic phenomena in the cytoskeleton and could apply to in vitro experiments as well as to stress fibers and to self-organization phenomena during cell locomotion.

Actin Cytoskeleton↗

PubMed2003

Motion of an adhesive gel in a swelling gradient: a mechanism for cell locomotion.

Motivated by the motion of nematode sperm cells, we present a model for the motion of an adhesive gel on a solid substrate. The gel polymerizes at the leading edge and depolymerizes at the rear. The motion results from a competition between a self-generated swelling gradient and the adhesion on the substrate. The resulting stress provokes the rupture of the adhesion points and allows for the motion. The model predicts an unusual force-velocity relation which depends in significant ways on the point of application of the force.

Adhesives↗

PubMed2003

Active traveling wave in the cochlea.

A sound stimulus entering the inner ear excites a deformation of the basilar membrane which travels along the cochlea towards the apex. It is well established that this wavelike disturbance is amplified by an active system. Recently, it has been proposed that the active system consists of a set of self-tuned critical oscillators which automatically operate at an oscillatory instability. Here, we show how the concepts of a traveling wave and of self-tuned critical oscillators can be combined to describe the nonlinear wave in the cochlea.

Basilar Membrane↗

PubMed2002

Formation and interaction of membrane tubes.

We show that the formation of membrane tubes (or membrane tethers), which is a crucial step in many biological processes, is highly nontrivial and involves first-order shape transitions. The force exerted by an emerging tube is a nonmonotonic function of its length. We point out that tubes attract each other, which eventually leads to their coalescence. We also show that detached tubes behave like semiflexible filaments with a rather short persistence length. We suggest that these properties play an important role in the formation and structure of tubular organelles.

Cell Membrane↗