@phdthesis{Mueller2008, author = {M{\"u}ller, Melanie J. I.}, title = {Bidirectional transport by molecular motors}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-18715}, school = {Universit{\"a}t Potsdam}, year = {2008}, abstract = {In biological cells, the long-range intracellular traffic is powered by molecular motors which transport various cargos along microtubule filaments. The microtubules possess an intrinsic direction, having a 'plus' and a 'minus' end. Some molecular motors such as cytoplasmic dynein walk to the minus end, while others such as conventional kinesin walk to the plus end. Cells typically have an isopolar microtubule network. This is most pronounced in neuronal axons or fungal hyphae. In these long and thin tubular protrusions, the microtubules are arranged parallel to the tube axis with the minus ends pointing to the cell body and the plus ends pointing to the tip. In such a tubular compartment, transport by only one motor type leads to 'motor traffic jams'. Kinesin-driven cargos accumulate at the tip, while dynein-driven cargos accumulate near the cell body. We identify the relevant length scales and characterize the jamming behaviour in these tube geometries by using both Monte Carlo simulations and analytical calculations. A possible solution to this jamming problem is to transport cargos with a team of plus and a team of minus motors simultaneously, so that they can travel bidirectionally, as observed in cells. The presumably simplest mechanism for such bidirectional transport is provided by a 'tug-of-war' between the two motor teams which is governed by mechanical motor interactions only. We develop a stochastic tug-of-war model and study it with numerical and analytical calculations. We find a surprisingly complex cooperative motility behaviour. We compare our results to the available experimental data, which we reproduce qualitatively and quantitatively.}, language = {en} } @phdthesis{Berger2012, author = {Berger, Florian}, title = {Different modes of cooperative transport by molecular motors}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-60319}, school = {Universit{\"a}t Potsdam}, year = {2012}, abstract = {Cargo transport by molecular motors is ubiquitous in all eukaryotic cells and is typically driven cooperatively by several molecular motors, which may belong to one or several motor species like kinesin, dynein or myosin. These motor proteins transport cargos such as RNAs, protein complexes or organelles along filaments, from which they unbind after a finite run length. Understanding how these motors interact and how their movements are coordinated and regulated is a central and challenging problem in studies of intracellular transport. In this thesis, we describe a general theoretical framework for the analysis of such transport processes, which enables us to explain the behavior of intracellular cargos based on the transport properties of individual motors and their interactions. Motivated by recent in vitro experiments, we address two different modes of transport: unidirectional transport by two identical motors and cooperative transport by actively walking and passively diffusing motors. The case of cargo transport by two identical motors involves an elastic coupling between the motors that can reduce the motors' velocity and/or the binding time to the filament. We show that this elastic coupling leads, in general, to four distinct transport regimes. In addition to a weak coupling regime, kinesin and dynein motors are found to exhibit a strong coupling and an enhanced unbinding regime, whereas myosin motors are predicted to attain a reduced velocity regime. All of these regimes, which we derive both by analytical calculations and by general time scale arguments, can be explored experimentally by varying the elastic coupling strength. In addition, using the time scale arguments, we explain why previous studies came to different conclusions about the effect and relevance of motor-motor interference. In this way, our theory provides a general and unifying framework for understanding the dynamical behavior of two elastically coupled molecular motors. The second mode of transport studied in this thesis is cargo transport by actively pulling and passively diffusing motors. Although these passive motors do not participate in active transport, they strongly enhance the overall cargo run length. When an active motor unbinds, the cargo is still tethered to the filament by the passive motors, giving the unbound motor the chance to rebind and continue its active walk. We develop a stochastic description for such cooperative behavior and explicitly derive the enhanced run length for a cargo transported by one actively pulling and one passively diffusing motor. We generalize our description to the case of several pulling and diffusing motors and find an exponential increase of the run length with the number of involved motors.}, language = {en} } @phdthesis{Bierbaum2011, author = {Bierbaum, Veronika}, title = {Chemomechanical coupling and motor cycles of the molecular motor myosin V}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-53614}, school = {Universit{\"a}t Potsdam}, year = {2011}, abstract = {In the living cell, the organization of the complex internal structure relies to a large extent on molecular motors. Molecular motors are proteins that are able to convert chemical energy from the hydrolysis of adenosine triphosphate (ATP) into mechanical work. Being about 10 to 100 nanometers in size, the molecules act on a length scale, for which thermal collisions have a considerable impact onto their motion. In this way, they constitute paradigmatic examples of thermodynamic machines out of equilibrium. This study develops a theoretical description for the energy conversion by the molecular motor myosin V, using many different aspects of theoretical physics. Myosin V has been studied extensively in both bulk and single molecule experiments. Its stepping velocity has been characterized as a function of external control parameters such as nucleotide concentration and applied forces. In addition, numerous kinetic rates involved in the enzymatic reaction of the molecule have been determined. For forces that exceed the stall force of the motor, myosin V exhibits a 'ratcheting' behaviour: For loads in the direction of forward stepping, the velocity depends on the concentration of ATP, while for backward loads there is no such influence. Based on the chemical states of the motor, we construct a general network theory that incorporates experimental observations about the stepping behaviour of myosin V. The motor's motion is captured through the network description supplemented by a Markov process to describe the motor dynamics. This approach has the advantage of directly addressing the chemical kinetics of the molecule, and treating the mechanical and chemical processes on equal grounds. We utilize constraints arising from nonequilibrium thermodynamics to determine motor parameters and demonstrate that the motor behaviour is governed by several chemomechanical motor cycles. In addition, we investigate the functional dependence of stepping rates on force by deducing the motor's response to external loads via an appropriate Fokker-Planck equation. For substall forces, the dominant pathway of the motor network is profoundly different from the one for superstall forces, which leads to a stepping behaviour that is in agreement with the experimental observations. The extension of our analysis to Markov processes with absorbing boundaries allows for the calculation of the motor's dwell time distributions. These reveal aspects of the coordination of the motor's heads and contain direct information about the backsteps of the motor. Our theory provides a unified description for the myosin V motor as studied in single motor experiments.}, language = {en} } @phdthesis{Kraikivski2005, author = {Kraikivski, Pavel}, title = {Non-equilibrium dynamics of adsorbed polymers and filaments}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-5979}, school = {Universit{\"a}t Potsdam}, year = {2005}, abstract = {In the present work, we discuss two subjects related to the nonequilibrium dynamics of polymers or biological filaments adsorbed to two-dimensional substrates. The first part is dedicated to thermally activated dynamics of polymers on structured substrates in the presence or absence of a driving force. The structured substrate is represented by double-well or periodic potentials. We consider both homogeneous and point driving forces. Point-like driving forces can be realized in single molecule manipulation by atomic force microscopy tips. Uniform driving forces can be generated by hydrodynamic flow or by electric fields for charged polymers. In the second part, we consider collective filament motion in motility assays for motor proteins, where filaments glide over a motor-coated substrate. The model for the simulation of the filament dynamics contains interactive deformable filaments that move under the influence of forces from molecular motors and thermal noise. Motor tails are attached to the substrate and modeled as flexible polymers (entropic springs), motor heads perform a directed walk with a given force-velocity relation. We study the collective filament dynamics and pattern formation as a function of the motor and filament density, the force-velocity characteristics, the detachment rate of motor proteins and the filament interaction. In particular, the formation and statistics of filament patterns such as nematic ordering due to motor activity or clusters due to blocking effects are investigated. Our results are experimentally accessible and possible experimental realizations are discussed.}, subject = {Polymere}, language = {en} } @phdthesis{Baczyński2009, author = {Baczyński, Krzysztof Konrad}, title = {Buckling instabilities of semiflexible filaments in biological systems}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-37927}, school = {Universit{\"a}t Potsdam}, year = {2009}, abstract = {In dieser Arbeit werden Knickinstabilit{\"a}ten von Filamenten in biologischen Systemen untersucht. Das Zytoskelett von Zellen ist aus solchen Filamenten aufgebaut. Sie sind f{\"u}r die mechanische Stabilit{\"a}t der Zelle verantwortlich und spielen eine große Rolle bei intrazellul{\"a}ren Transportprozessen durch molekulare Motoren, die verschiedene Lasten wie beispielsweise Organellen entlang der Filamente des Zytoskeletts transportieren. Filamente sind semiflexible Polymere, deren Biegeenergie {\"a}hnlich groß ist wie die thermische Energie, so dass sie auch als elastische Balken auf der Nanoskala gesehen werden k{\"o}nnen, die signifikante thermische Fluktuationen zeigen. Wie ein makroskopischer elastischer Balken k{\"o}nnen auch Filamente eine mechanische Knickinstabilit{\"a}t unter Kompression zeigen. Im ersten Teil dieser Arbeit wird untersucht, wie diese Instabilit{\"a}t durch thermische Fluktuationen der Filamente beeinflusst wird. In Zellen k{\"o}nnen Kompressionskr{\"a}fte durch molekulare Motoren erzeugt werden. Das geschieht zum Beispiel w{\"a}hrend der Zellteilung in der mitotischen Spindel. Im zweiten Teil der Arbeit untersuchen wir, wie die stochastische Natur einer von Motoren generierten Kraft die Knickinstabilit{\"a}t von Filamenten beeinflusst. Zun{\"a}chst stellen wir kurz das Problem von Knickinstabilit{\"a}ten auf der makroskopischen Skala dar und f{\"u}hren ein Modell f{\"u}r das Knicken von Filamenten oder elastischen St{\"a}ben in zwei Raumdimensionen und in Anwesenheit thermischer Fluktuationen ein. Wir pr{\"a}sentieren eine analytische L{\"o}sung f{\"u}r Knickinstabilit{\"a}ten in Anwesenheit thermischer Fluktuationen, die auf einer Renormierungsgruppenrechnung im Rahmen des nichtlinearen Sigma-Models basiert. Wir integrieren die kurzwelligen Fluktuationen aus, um eine effektive Theorie f{\"u}r die langwelligen Moden zu erhalten, die die Knickinstabilit{\"a}t bestimmen. Wir berechnen die {\"A}nderung der kritischen Kraft f{\"u}r die Knickinstabilit{\"a}t und zeigen, dass die thermischen Fluktuationen in zwei Raumdimensionen zu einer Zunahme der kritischen Kraft f{\"u}hren. Außerdem zeigen wir, dass thermische Fluktuationen im geknickten Zustand zu einer Zunahme der mittleren projizierten L{\"a}nge des Filaments in Richtung der wirkenden Kraft f{\"u}hren. Als Funktion der Konturl{\"a}nge des Filaments besitzt die mittlere projizierte L{\"a}nge eine Spitze an der Knickinstabilit{\"a}t, die durch thermische Fluktuationen abgerundet wird. Unser Hauptresultat ist die Beobachtung, dass ein geknicktes Filament unter dem Einfluss thermischer Fluktuationen gestreckt wird, d.h. dass seine mittlere projizierte L{\"a}nge in Richtung der Kompressionskraft auf Grund der thermischen Fluktuationen zunimmt. Unsere analytischen Resultate werden durch Monte-Carlo Simulationen der Knickinstabilit{\"a}t semiflexibler Filamente in zwei Raumdimensionen best{\"a}tigt. Wir f{\"u}hren auch Monte-Carlo Simulationen in h{\"o}heren Raumdimensionen durch und zeigen, dass die Zunahme der projizierten L{\"a}nge unter dem Einfluss thermischer Fluktuationen weniger ausgepr{\"a}gt ist und stark von der Wahl der Randbedingungen abh{\"a}ngt. Im zweiten Teil der Arbeit formulieren wir ein Modell f{\"u}r die Knickinstabilit{\"a}t semiflexibler Filamente unter dem Einfluss molekularer Motoren. Wir untersuchen ein System, in dem sich eine Gruppe von Motoren entlang eines fixierten Filaments bewegt, und dabei ein zweites Filament als Last tr{\"a}gt. Das Last-Filament wird gegen eine Wand gedr{\"u}ckt und knickt. W{\"a}hrend des Knickvorgangs k{\"o}nnen die Motoren, die die Kraft auf das Filament generieren, stochastisch von dem Filament ab- und an das Filament anbinden. Wir formulieren ein stochastisches Model f{\"u}r dieses System und berechnen die "mean first passage time", d.h. die mittlere Zeit f{\"u}r den {\"U}bergang von einem Zustand, in dem alle Motoren gebundenen sind zu einem Zustand, in dem alle Motoren abgebunden sind. Dieser {\"U}bergang entspricht auch einem {\"U}bergang aus dem gebogenen zur{\"u}ck in einen ungebogenen Zustand des Last-Filaments. Unser Resultat zeigt, dass f{\"u}r gen{\"u}gend kurze Mikrotubuli die Bewegung der Motoren von der durch das Last-Filament generierten Kraft beeinflusst wird. Diese Ergebnisse k{\"o}nnen in zuk{\"u}nftigen Experimenten {\"u}berpr{\"u}ft werden.}, language = {en} } @phdthesis{Klumpp2003, author = {Klumpp, Stefan}, title = {Movements of molecular motors : diffusion and directed walks}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-0000806}, school = {Universit{\"a}t Potsdam}, year = {2003}, abstract = {Bewegungen von prozessiven molekularen Motoren des Zytoskeletts sind durch ein Wechselspiel von gerichteter Bewegung entlang von Filamenten und Diffusion in der umgebenden L{\"o}sung gekennzeichnet. Diese eigent{\"u}mlichen Bewegungen werden in der vorliegenden Arbeit untersucht, indem sie als Random Walks auf einem Gitter modelliert werden. Ein weiterer Gegenstand der Untersuchung sind Effekte von Wechselwirkungen zwischen den Motoren auf diese Bewegungen. Im einzelnen werden vier Transportph{\"a}nomene untersucht: (i) Random Walks von einzelnen Motoren in Kompartimenten verschiedener Geometrien, (ii) station{\"a}re Konzentrationsprofile, die sich in geschlossenen Kompartimenten infolge dieser Bewegungen einstellen, (iii) randinduzierte Phasen{\"u}berg{\"a}nge in offenen r{\"o}hrenartigen Kompartimenten, die an Motorenreservoirs gekoppelt sind, und (iv) der Einfluß von kooperativen Effekten bei der Motor-Filament-Bindung auf die Bewegung. Alle diese Ph{\"a}nomene sind experimentell zug{\"a}nglich, und m{\"o}gliche experimentelle Realisierungen werden diskutiert.}, language = {en} }