Cette thèse est consacrée à l'étude des applications de la théorie des erreurs par formes de Dirichlet. Notre travail se divise en trois parties. La première analyse les modèles gouvernés par une équation différentielle stochastique. Après un court chapitre technique, un modèle innovant pour les carnets d’ordres est proposé. Nous considérons que le spread bid-ask n'est pas un défaut, mais plutôt une propriété intrinsèque du marché. L'incertitude est portée par le mouvement Brownien qui conduit l'actif. Nous montrons que l'évolution des spread peut être évaluée grâce à des formules fermées et nous étudions l'impact de l'incertitude du sous-jacent sur les produits dérivés. En suite, nous introduisons le modèle PBS pour le pricing des options européennes. L'idée novatrice est de distinguer la volatilité du marché par rapport au paramètre utilisé par les traders pour se couvrir. Nous assumons la première constante, alors que le deuxième devient une estimation subjective et erronée de la première. Nous prouvons que ce modèle prévoit un spread bid-ask et un smile de volatilité. Les propriétés plus intéressantes de ce modèle sont l’existence de formules fermés pour le pricing, l'impact de la dérive du sous-jacent et une efficace stratégie de calibration. La seconde partie s'intéresse aux modèles décrit par une équation aux dérivées partielles. Les cas linéaire et non-linéaire sont analysés séparément. Dans le premier nous montrons des relations intéressantes entre la théorie des erreurs et celui des ondelettes. Dans le cas non-linéaire nous étudions la sensibilité des solutions à l’aide de la théorie des erreurs. Sauf dans le cas d’une solution exacte, il y a deux approches possibles : on peut d’abord discrétiser l’EDP et étudier la sensibilité du problème discrétisé, soit démontrer que les sensibilités théoriques vérifient des EDP. Les deux cas sont étudiés, et nous prouvons que les sharp et le biais sont solutions d’EDP linéaires dépendantes de la solution de l’EDP originaire et nous proposons des algorithmes pour évaluer numériquement les sensibilités. Enfin, la troisième partie est dédiée aux équations stochastiques aux dérivées partielles. Notre analyse se divise en deux chapitres. D’abord nous étudions la transmission de l’incertitude, présente dans la condition initiale, à la solution de l’EDPS. En suite, nous analysons l'impact d'une perturbation dans les termes fonctionnelles de l’EDPS et dans le coefficient de la fonction de Green associée. Dans le deux cas, nous prouvons que le sharp et le biais sont solutions de deux EDPS linéaires dépendantes de la solution de l’EDPS originaire / This thesis is devoted to the study of the applications of the error theory using Dirichlet forms. Our work is split into three parts. The first one deals with the models described by stochastic differential equations. After a short technical chapter, an innovative model for order books is proposed. We assume that the bid-ask spread is not an imperfection, but an intrinsic property of exchange markets instead. The uncertainty is carried by the Brownian motion guiding the asset. We find that spread evolutions can be evaluated using closed formulae and we estimate the impact of the underlying uncertainty on the related contingent claims. Afterwards, we deal with the PBS model, a new model to price European options. The seminal idea is to distinguish the market volatility with respect to the parameter used by traders for hedging. We assume the former constant, while the latter volatility being an erroneous subjective estimation of the former. We prove that this model anticipates a bid-ask spread and a smiled implied volatility curve. Major properties of this model are the existence of closed formulae for prices, the impact of the underlying drift and an efficient calibration strategy. The second part deals with the models described by partial differential equations. Linear and non-linear PDEs are examined separately. In the first case, we show some interesting relations between the error and wavelets theories. When non-linear PDEs are concerned, we study the sensitivity of the solution using error theory. Except when exact solution exists, two possible approaches are detailed: first, we analyze the sensitivity obtained by taking “derivatives” of the discrete governing equations. Then, we study the PDEs solved by the sensitivity of the theoretical solutions. In both cases, we show that sharp and bias solve linear PDE depending on the solution of the former PDE itself and we suggest algorithms to evaluate numerically the sensitivities. Finally, the third part is devoted to stochastic partial differential equations. Our analysis is split into two chapters. First, we study the transmission of an uncertainty, present on starting conditions, on the solution of SPDE. Then, we analyze the impact of a perturbation of the functional terms of SPDE and the coefficient of the related Green function. In both cases, we show that the sharp and bias verify linear SPDE depending on the solution of the former SPDE itself / Questa tesi é dedicata allo studio delle applicazioni della teoria degli errori tramite forme di Dirichlet, il nostro lavoro si divide in tre parti. Nella prima vengono studiati i modelli descritti da un’equazione differenziale stocastica: dopo un breve capitolo con risultati tecnici viene descritto un modello innovativo per i libri d’ordini. La presenza dei differenziali denarolettera viene considerata non come un’imperfezione, bensi una proprietà intrinseca dei mercati. L’incertezza viene descritta come un rumore sul moto Browniano sottostante all’azione; dimostriamo che l’evoluzione di questi differenziali puó essere valutata attraverso formule chiuse e stimiamo l’impatto dell’incertezza del sottostante sui prodotti derivati. In seguito proponiamo un nuovo modello, chiamato PBS, per il prezzaggio delle opzioni di tipo europeo: l’idea innovativa consiste nel distinguere la volatilità di mercato dal parametro usato dai trader per la copertura. Noi supponiamo la prima constante, mentre il secondo diventa una stima soggettiva ed erronea della prima. Dimostriamo che questo modello prevede dei differenziali lettera-denaro e uno smile di volatilità implicita. Le maggiori proprietà di questo modello sono l’esistenza di formule chiuse per il princing, l’impatto del drift del sottostante e un’efficace strategia per la calibrazione. La seconda parte è dedicata allo studio dei modelli descritti da delle equazioni alle derivate perziali. I casi lineare e non-lineare sono trattati separatamente. Nel primo caso mostriamo interessanti relazioni tra la teoria degli errori e quella delle wavelets. Nel caso delle EDP non-lineari studiamo la sensibilità della soluzione usando la teoria degli errori. Due possibili approcci esistono, salvo quando la soluzione è esplicita. Possiamo prima discretizzare il problema e studiare la sensibilità delle equazioni discretizzate, oppure possiamo dimostrare che le sensibilità teoriche verificano, a loro volta, delle EDP dipendenti dalla soluzione della EDP iniziale. Entrambi gli approcci sono descritti e vengono proposti degli algoritmi per valutare le sensibilità numericamente. Infine, la terza parte è dedicata ai modelli descritti da un’equazione stocastica alle derivate parziali. La nostra analisi é divisa in due capitoli. Nel primo viene studiato l’impatto di un’incertezza, presente nella condizione iniziale, sulla soluzione dell’EDPS, nella seconda si analizzano gli impatti di una perturbazione dei termini funzionali dell’EDPS del coefficiente della funzione di Green associata. In entrambi i casi dimostriamo che lo sharp e la discrepanza sono soluzioni di due EDPS lineari dipendenti dalla soluzione dell’EDPS iniziale

Nous nous intéressons à des équations différentielles stochastiques obtenues en perturbant par un bruit blanc des équations différentielles ordinaires admettant N orbites périodiques asymptotiquement stables. Nous construisons une chaîne de Markov à temps discret et espace d’états continu appelée application de Poincaré aléatoire qui hérite du comportement métastable du système. Nous montrons que ce processus admet exactement N valeurs propres qui sont exponentiellement proches de 1 et nous donnons des expressions pour ces valeurs propres et les fonctions propres associées en termes de fonctions committeurs dans les voisinages des orbites périodiques. Nous montrons également que ces valeurs propres sont bien séparées du reste du spectre. Chacune de ces valeurs propres exponentiellement proche de 1 est également reliée à un temps d’atteinte de ces voisinages. De plus, les N valeurs propres exponentiellement proches de 1 et fonctions propres à gauche et à droite associées peuvent être respectivement approchées par des valeurs propres principales, des distributions quasi-stationnaires, et des fonctions propres principales à droite de processus tués quand ils atteignent ces voisinages. Les preuves reposent sur une représentation de type Feynman–Kac pour les fonctions propres, la transformée harmonique de Doob, la théorie spectrale des opérateurs compacts et une propriété de type équilibré détaillé satisfaite par les fonctions committeurs. / We consider stochastic differential equations, obtained by adding weak Gaussian white noise to ordinary differential equations admitting N asymptotically stable periodic orbits. We construct a discrete-time,continuous-space Markov chain, called a random Poincaré map, which encodes the metastable behaviour of the system. We show that this process admits exactly N eigenvalues which are exponentially close to 1,and provide expressions for these eigenvalues and their left and right eigenfunctions in terms of committorfunctions of neighbourhoods of periodic orbits. We also provide a bound for the remaining part of the spectrum. The eigenvalues that are exponentially close to 1 and the right and left eigenfunctions are well-approximated by principal eigenvalues, quasistationary distributions, and principal right eigenfunctions of processes killed upon hitting some of these neighbourhoods. Each eigenvalue that is exponentially close to 1is also related to the mean exit time from some metastable neighborhood of the periodic orbits. The proofsrely on Feynman–Kac-type representation formulas for eigenfunctions, Doob’s h-transform, spectral theory of compact operators, and a recently discovered detailed balance property satisfied by committor functions.

Financial processes may possess long memory and their probability densities may display heavy tails. Many models have been developed to deal with this tail behaviour, which reflects the jumps in the sample paths. On the other hand, the presence of long memory, which contradicts the efficient market hypothesis, is still an issue for further debates. These difficulties present challenges with the problems of memory detection and modelling the co-presence of long memory and heavy tails. This PhD project aims to respond to these challenges. The first part aims to detect memory in a large number of financial time series on stock prices and exchange rates using their scaling properties. Since financial time series often exhibit stochastic trends, a common form of nonstationarity, strong trends in the data can lead to false detection of memory. We will take advantage of a technique known as multifractal detrended fluctuation analysis (MF-DFA) that can systematically eliminate trends of different orders. This method is based on the identification of scaling of the q-th-order moments and is a generalisation of the standard detrended fluctuation analysis (DFA) which uses only the second moment; that is, q = 2. We also consider the rescaled range R/S analysis and the periodogram method to detect memory in financial time series and compare their results with the MF-DFA. An interesting finding is that short memory is detected for stock prices of the American Stock Exchange (AMEX) and long memory is found present in the time series of two exchange rates, namely the French franc and the Deutsche mark. Electricity price series of the five states of Australia are also found to possess long memory. For these electricity price series, heavy tails are also pronounced in their probability densities. The second part of the thesis develops models to represent short-memory and longmemory financial processes as detected in Part I. These models take the form of continuous-time AR(∞) -type equations whose kernel is the Laplace transform of a finite Borel measure. By imposing appropriate conditions on this measure, short memory or long memory in the dynamics of the solution will result. A specific form of the models, which has a good MA(∞) -type representation, is presented for the short memory case. Parameter estimation of this type of models is performed via least squares, and the models are applied to the stock prices in the AMEX, which have been established in Part I to possess short memory. By selecting the kernel in the continuous-time AR(∞) -type equations to have the form of Riemann-Liouville fractional derivative, we obtain a fractional stochastic differential equation driven by Brownian motion. This type of equations is used to represent financial processes with long memory, whose dynamics is described by the fractional derivative in the equation. These models are estimated via quasi-likelihood, namely via a continuoustime version of the Gauss-Whittle method. The models are applied to the exchange rates and the electricity prices of Part I with the aim of confirming their possible long-range dependence established by MF-DFA. The third part of the thesis provides an application of the results established in Parts I and II to characterise and classify financial markets. We will pay attention to the New York Stock Exchange (NYSE), the American Stock Exchange (AMEX), the NASDAQ Stock Exchange (NASDAQ) and the Toronto Stock Exchange (TSX). The parameters from MF-DFA and those of the short-memory AR(∞) -type models will be employed in this classification. We propose the Fisher discriminant algorithm to find a classifier in the two and three-dimensional spaces of data sets and then provide cross-validation to verify discriminant accuracies. This classification is useful for understanding and predicting the behaviour of different processes within the same market. The fourth part of the thesis investigates the heavy-tailed behaviour of financial processes which may also possess long memory. We consider fractional stochastic differential equations driven by stable noise to model financial processes such as electricity prices. The long memory of electricity prices is represented by a fractional derivative, while the stable noise input models their non-Gaussianity via the tails of their probability density. A method using the empirical densities and MF-DFA will be provided to estimate all the parameters of the model and simulate sample paths of the equation. The method is then applied to analyse daily spot prices for five states of Australia. Comparison with the results obtained from the R/S analysis, periodogram method and MF-DFA are provided. The results from fractional SDEs agree with those from MF-DFA, which are based on multifractal scaling, while those from the periodograms, which are based on the second order, seem to underestimate the long memory dynamics of the process. This highlights the need and usefulness of fractal methods in modelling non-Gaussian financial processes with long memory.

In this thesis, we present a new existence result for Lévy-type processes. Lévy-type processes behave locally like a Lévy process, but the Lévy triplet may depend on the current position of the process. They can be characterized by their so-called symbol; this is the analogue of the characteristic exponent in the Lévy case. Using a parametrix construction, we prove the existence of Lévy-type processes with a given symbol under weak regularity assumptions on the regularity of the symbol. Applications range from existence results for stable-like processes and mixed processes to uniqueness results for Lévy-driven stochastic differential equations. Moreover, we discuss sufficient conditions for the existence of moments of Lévy-type processes and derive estimates for fractional moments.

Nous nous intéressons dans cette thèse à certains modèles mathématiques permettant une description de systèmes ouverts classiques et quantiques. Dans l'étude de ces systèmes en interaction avec un environnement, nous montrons que la dynamique induite par l'environnement sur le système donne lieu à l'apparition de bruits. Dans une première partie de la thèse, dédiée aux systèmes classiques, le modèle décrit est le schéma d'interactions répétées. Etant à la fois hamiltonien et markovien, ce modèle en temps discret permet d'implémenter facilement la dissipation dans des systèmes physiques. Nous expliquons comment le mettre en place pour des systèmes physiques avant d'en étudier la limite en temps continu. Nous montrons la convergence Lp et presque sûre de l'évolution de certains systèmes vers la solution d'une équation différentielle stochastique, à travers l'étude de la limite de la perturbation d'un schéma d'Euler stochastique. Dans une seconde partie de la thèse sur les systèmes quantiques, nous nous intéressons dans un premier temps aux actions d'environnements quantiques sur des systèmes quantiques aboutissant à des bruits classiques. A cette fin, nous introduisons certains opérateurs unitaires appelés « classiques », que nous caractérisons à l'aide de variables aléatoires dites obtuses. Nous mettons en valeur comment ces variables classiques apparaissent naturellement dans ce cadre quantique à travers des 3-tenseurs possédant des symétries particulières. Nous prouvons notamment que ces 3-tenseurs sont exactement ceux diagonalisables dans une base orthonormée. Dans un second temps, nous étudions la limite en temps continu d'une variante des interactions répétées quantiques dans le cas particulier d'un système biparti, c'est-à-dire composé de deux systèmes isolés sans interaction entre eux. Nous montrons qu'à la limite du temps continu, une interaction entre ces sous-systèmes apparaît explicitement sous forme d'un hamiltonien d'interaction; cette interaction résulte de l'action de l'environnement et de l'intrication qu'il crée / This dissertation is dedicated to some mathematical models describing classical and quantum open systems. In the study of these systems interacting with an environment, we particularly show that the dynamics induced by the environment leads to the appearance of noises. In a first part of this thesis, devoted to classical open systems, the repeated interaction scheme is developed. This discrete-time model, being Hamiltonian and Markovian at the same time, has the advantage to easily implement the dissipation in physical systems. We explain how to set this scheme up in some physical examples. Then, we investigate the continuous-time limit of these repeated interactions. We show the Lp and almost sure convergences of the evolution of the system to the solution of a stochastic differential equation, by studying the limit of a perturbed Stochastic Euler Scheme. In a second part of this dissertation on quantum systems, we characterize in a first work classical actions of a quantum environment on a quantum system. In this study, we introduce some “classical” unitary operators representing these actions and we highlight a strong link between them and some random variables, called obtuse random variables. We explain how these random variables are naturally connected to some 3-tensors having some particular symmetries. We particularly show that these 3 tensors are exactly the ones that are diagonalizable in some orthonormal basis. In a second work of this part, we study the continuous-time limit of a variant of the repeated interaction scheme in a case of a bipartite system, that is, a system made of two isolated systems not interaction together. We prove that an explicit Hamiltonian interaction between them appears at the limit. This interaction is due to the action of the environment and the entanglement between the two systems that it creates

Economic uncertainty may affect significantly people’s behavior and hence macroeconomic variables. It is thus important to understand how people behave in presence of different kinds of economic risk. The present dissertation focuses therefore on the impact of the uncertainty in capital and labor income on the individual saving behavior. The underlying uncertain variables are here modeled as stochastic processes that each obey a specific stochastic differential equation, where uncertainty stems either from Poisson or Lévy processes. The results on the optimal behavior are derived by maximizing the individual expected lifetime utility. The first chapter is concerned with the necessary mathematical tools, the change-of-variables formula and the Hamilton-Jacobi-Bellman equation under Poisson uncertainty. We extend their possible field of application in order make them appropriate for the analysis of the dynamic stochastic optimization problems occurring in the following chapters and elsewhere. The second chapter considers an optimum-saving problem with labor income, where capital risk stems from asset prices that follow geometric L´evy processes. Chapter 3, finally, studies the optimal saving behavior if agents face not only risk but also uncertain spells of unemployment. To this end, we turn back to Poisson processes, which here are used to model properly the separation and matching process.

In dieser Arbeit betrachten wir das Strömungs-Diffusions-(Reaktions)-Problem für passive Markerteilchen, die in zweidimensionalen laminaren Strömungsmustern mit geringem thermischem Rauschen gelöst sind. Der deterministische Fluss umfasst Zellen in Form von Quadraten oder Katzenaugen. In ihnen tritt Rotationsbewegung auf. Einige der Strömungen bestehen aus wellenförmigen Bereichen mit gerader Vorwärtsbewegung. Alle Systeme sind entweder periodisch oder durch Wände begrenzt. Eine untersuchte Familie von Strömungen interpoliert kontinuierlich zwischen Reihen von Wirbeln und Scherflüssen. Wir analysieren zahlreiche numerische Simulationen, die bisherige theoretische Vorhersagen bestätigen und neue Phänomene offenbaren. Ohne Rauschen sind die Teilchen in einzelnen Bestandteilen des Flusses für immer gefangen. Durch Hinzufügen von schwachem thermischen Rauschen wird die normale Diffusion für lange Zeiten stark verstärkt und führt zu verschiedenen Diffusionsarten für mittlere Zeiten. Mit Continuous-Time-Random-Walk-Modellen leiten wir analytische Ausdrücke in Übereinstimmung mit den numerischen Ergebnissen her, die je nach Parametern, Anfangsbedingungen und Alterungszeiten von subdiffusiver bis superballistischer anomaler Diffusion für mittlere Zeiten reichen. Wir sehen deutlich, dass einige der früheren Vorhersagen nur für Teilchen gelten, die an der Separatrix des Flusses starten - der einzige Fall, der in der Vergangenheit ausführlich betrachtet wurde - und dass das System zu vollkommen anderem Verhalten in anderen Situationen führen kann, einschließlich einem Schwingenden beim Start im Zentrum einesWirbels nach einer gewissen Alterungszeit. Darüber hinaus enthüllen die Simulationen, dass Teilchenreaktionen dort häufiger auftreten, wo sich die Geschwindigkeit der Strömung stark ändert, was dazu führt, dass langsame Teilchen von schnelleren getroffen werden, die ihnen folgen. Die umfangreichen numerischen Simulationen, die für diese Arbeit durchgeführt wurden, mussten jetzt durchgeführt werden, da wir die Rechenleistung dafür besitzen. / In this thesis, we consider the advection-diffusion-(reaction) problem for passive tracer particles suspended in two-dimensional laminar flow patterns with small thermal noise. The deterministic flow comprises cells in the shape of either squares or cat’s eyes. Rotational motion occurs inside them. Some of the flows consist of sinusoidal regions of straight forward motion. All systems are either periodic or are bounded by walls. One examined family of flows continuously interpolates between arrays of eddies and shear flows. We analyse extensive numerical simulations, which confirm previous theoretical predictions as well as reveal new phenomena. Without noise, particles are trapped forever in single building blocks of the flow. Adding small thermal noise, leads to largely enhanced normal diffusion for long times and several kinds of diffusion for intermediate times. Using continuous time random walk models, we derive analytical expressions in accordance with numerical results, ranging from subdiffusive to superballistic anomalous diffusion for intermediate times depending on parameters, initial conditions and aging time. We clearly see, that some of the previous predictions are only true for particles starting at the separatrix of the flow - the only case considered in depth in the past - and that the system might show a vastly different behavior in other situations, including an oscillatory one, when starting in the center of an eddy after a certain aging time. Furthermore, simulations reveal that particle reactions occur more frequently at positions where the velocity of the flow changes the most, resulting in slow particles being hit by faster ones following them. The extensive numerical simulations performed for this thesis had to be done now that we have the computational means to do so. Machines are powerful tools in order to gain a deeper and more detailed insight into the dynamics of many complicated dynamical and stochastic systems.

<div>The rise of artificial intelligence (AI) hinges on the efficient training of modern deep neural networks (DNNs) for non-convex optimization and uncertainty quantification, which boils down to a non-convex Bayesian learning problem. A standard tool to handle the problem is Langevin Monte Carlo, which proposes to approximate the posterior distribution with theoretical guarantees. However, non-convex Bayesian learning in real big data applications can be arbitrarily slow and often fails to capture the uncertainty or informative modes given a limited time. As a result, advanced techniques are still required.</div><div><br></div><div>In this thesis, we start with the replica exchange Langevin Monte Carlo (also known as parallel tempering), which is a Markov jump process that proposes appropriate swaps between exploration and exploitation to achieve accelerations. However, the na\"ive extension of swaps to big data problems leads to a large bias, and the bias-corrected swaps are required. Such a mechanism leads to few effective swaps and insignificant accelerations. To alleviate this issue, we first propose a control variates method to reduce the variance of noisy energy estimators and show a potential to accelerate the exponential convergence. We also present the population-chain replica exchange and propose a generalized deterministic even-odd scheme to track the non-reversibility and obtain an optimal round trip rate. Further approximations are conducted based on stochastic gradient descents, which yield a user-friendly nature for large-scale uncertainty approximation tasks without much tuning costs. </div><div><br></div><div>In the second part of the thesis, we study scalable dynamic importance sampling algorithms based on stochastic approximation. Traditional dynamic importance sampling algorithms have achieved successes in bioinformatics and statistical physics, however, the lack of scalability has greatly limited their extensions to big data applications. To handle this scalability issue, we resolve the vanishing gradient problem and propose two dynamic importance sampling algorithms based on stochastic gradient Langevin dynamics. Theoretically, we establish the stability condition for the underlying ordinary differential equation (ODE) system and guarantee the asymptotic convergence of the latent variable to the desired fixed point. Interestingly, such a result still holds given non-convex energy landscapes. In addition, we also propose a pleasingly parallel version of such algorithms with interacting latent variables. We show that the interacting algorithm can be theoretically more efficient than the single-chain alternative with an equivalent computational budget.</div>

The present habilitation thesis in theoretical biological physics addresses two central dynamical processes in cells and organisms: (i) active motility and motility control and (ii) self-organized pattern formation. The unifying theme is the nonlinear dynamics of biological function and its robustness in the presence of strong fluctuations, structural variations, and external perturbations. We theoretically investigate motility control at the cellular scale, using cilia and flagella as ideal model system. Cilia and flagella are highly conserved slender cell appendages that exhibit spontaneous bending waves. This flagellar beat represents a prime example of a chemo-mechanical oscillator, which is driven by the collective dynamics of molecular motors inside the flagellar axoneme. We study the nonlinear dynamics of flagellar swimming, steering, and synchronization, which encompasses shape control of the flagellar beat by chemical signals and mechanical forces. Mechanical forces can synchronize collections of flagella to beat at a common frequency, despite active motor noise that tends to randomize flagellar synchrony. In Chapter 2, we present a new physical mechanism for flagellar synchronization by mechanical self-stabilization that applies to free-swimming flagellated cells. This new mechanism is independent of direct hydrodynamic interactions between flagella. Comparison with experimental data provided by experimental collaboration partners in the laboratory of J. Howard (Yale, New Haven) confirmed our new mechanism in the model organism of the unicellular green alga Chlamydomonas. Further, we characterize the beating flagellum as a noisy oscillator. Using a minimal model of collective motor dynamics, we argue that measured non-equilibrium fluctuations of the flagellar beat result from stochastic motor dynamics at the molecular scale. Noise and mechanical coupling are antagonists for flagellar synchronization. In addition to the control of the flagellar beat by mechanical forces, we study the control of the flagellar beat by chemical signals in the context of sperm chemotaxis. We characterize a fundamental paradigm for navigation in external concentration gradients that relies on active swimming along helical paths. In this helical chemotaxis, the direction of a spatial concentration gradient becomes encoded in the phase of an oscillatory chemical signal. Helical chemotaxis represents a distinct gradient-sensing strategy, which is different from bacterial chemotaxis. Helical chemotaxis is employed, for example, by sperm cells from marine invertebrates with external fertilization. We present a theory of sensorimotor control, which combines hydrodynamic simulations of chiral flagellar swimming with a dynamic regulation of flagellar beat shape in response to chemical signals perceived by the cell. Our theory is compared to three-dimensional tracking experiments of sperm chemotaxis performed by the laboratory of U. B. Kaupp (CAESAR, Bonn). In addition to motility control, we investigate in Chapter 3 self-organized pattern formation in two selected biological systems at the cell and organism scale, respectively. On the cellular scale, we present a minimal physical mechanism for the spontaneous self-assembly of periodic cytoskeletal patterns, as observed in myofibrils in striated muscle cells. This minimal mechanism relies on the interplay of a passive coarsening process of crosslinked actin clusters and active cytoskeletal forces. This mechanism of cytoskeletal pattern formation exemplifies how local interactions can generate large-scale spatial order in active systems. On the organism scale, we present an extension of Turing’s framework for self-organized pattern formation that is capable of a proportionate scaling of steady-state patterns with system size. This new mechanism does not require any pre-pattering clues and can restore proportional patterns in regeneration scenarios. We analytically derive the hierarchy of steady-state patterns and analyze their stability and basins of attraction. We demonstrate that this scaling mechanism is structurally robust. Applications to the growth and regeneration dynamics in flatworms are discussed (experiments by J. Rink, MPI CBG, Dresden). / Das Thema der vorliegenden Habilitationsschrift in Theoretischer Biologischer Physik ist die nichtlineare Dynamik funktionaler biologischer Systeme und deren Robustheit gegenüber Fluktuationen und äußeren Störungen. Wir entwickeln hierzu theoretische Beschreibungen für zwei grundlegende biologische Prozesse: (i) die zell-autonome Kontrolle aktiver Bewegung, sowie (ii) selbstorganisierte Musterbildung in Zellen und Organismen. In Kapitel 2, untersuchen wir Bewegungskontrolle auf zellulärer Ebene am Modelsystem von Zilien und Geißeln. Spontane Biegewellen dieser dünnen Zellfortsätze ermöglichen es eukaryotischen Zellen, in einer Flüssigkeit zu schwimmen. Wir beschreiben einen neuen physikalischen Mechanismus für die Synchronisation zweier schlagender Geißeln, unabhängig von direkten hydrodynamischen Wechselwirkungen. Der Vergleich mit experimentellen Daten, zur Verfügung gestellt von unseren experimentellen Kooperationspartnern im Labor von J. Howard (Yale, New Haven), bestätigt diesen neuen Mechanismus im Modellorganismus der einzelligen Grünalge Chlamydomonas. Der Gegenspieler dieser Synchronisation durch mechanische Kopplung sind Fluktuationen. Wir bestimmen erstmals Nichtgleichgewichts-Fluktuationen des Geißel-Schlags direkt, wofür wir eine neue Analyse-Methode der Grenzzykel-Rekonstruktion entwickeln. Die von uns gemessenen Fluktuationen entstehen mutmaßlich durch die stochastische Dynamik molekularen Motoren im Innern der Geißeln, welche auch den Geißelschlag antreiben. Um die statistische Physik dieser Nichtgleichgewichts-Fluktuationen zu verstehen, entwickeln wir eine analytische Theorie der Fluktuationen in einem minimalen Modell kollektiver Motor-Dynamik. Zusätzlich zur Regulation des Geißelschlags durch mechanische Kräfte untersuchen wir dessen Regulation durch chemische Signale am Modell der Chemotaxis von Spermien-Zellen. Dabei charakterisieren wir einen grundlegenden Mechanismus für die Navigation in externen Konzentrationsgradienten. Dieser Mechanismus beruht auf dem aktiven Schwimmen entlang von Spiralbahnen, wodurch ein räumlicher Konzentrationsgradient in der Phase eines oszillierenden chemischen Signals kodiert wird. Dieser Chemotaxis-Mechanismus unterscheidet sich grundlegend vom bekannten Chemotaxis-Mechanismus von Bakterien. Wir entwickeln eine Theorie der senso-motorischen Steuerung des Geißelschlags während der Spermien-Chemotaxis. Vorhersagen dieser Theorie werden durch Experimente der Gruppe von U.B. Kaupp (CAESAR, Bonn) quantitativ bestätigt. In Kapitel 3, untersuchen wir selbstorganisierte Strukturbildung in zwei ausgewählten biologischen Systemen. Auf zellulärer Ebene schlagen wir einen einfachen physikalischen Mechanismus vor für die spontane Selbstorganisation von periodischen Zellskelett-Strukturen, wie sie sich z.B. in den Myofibrillen gestreifter Muskelzellen finden. Dieser Mechanismus zeigt exemplarisch auf, wie allein durch lokale Wechselwirkungen räumliche Ordnung auf größeren Längenskalen in einem Nichtgleichgewichtssystem entstehen kann. Auf der Ebene des Organismus stellen wir eine Erweiterung der Turingschen Theorie für selbstorganisierte Musterbildung vor. Wir beschreiben eine neue Klasse von Musterbildungssystemen, welche selbst-organisierte Muster erzeugt, die mit der Systemgröße skalieren. Dieser neue Mechanismus erfordert weder eine vorgegebene Kompartimentalisierung des Systems noch spezielle Randbedingungen. Insbesondere kann dieser Mechanismus proportionale Muster wiederherstellen, wenn Teile des Systems amputiert werden. Wir bestimmen analytisch die Hierarchie aller stationären Muster und analysieren deren Stabilität und Einzugsgebiete. Damit können wir zeigen, dass dieser Skalierungs-Mechanismus strukturell robust ist bezüglich Variationen von Parametern und sogar funktionalen Beziehungen zwischen dynamischen Variablen. Zusammen mit Kollaborationspartnern im Labor von J. Rink (MPI CBG, Dresden) diskutieren wir Anwendungen auf das Wachstum von Plattwürmern und deren Regeneration in Amputations-Experimenten.

The present habilitation thesis in theoretical biological physics addresses two central dynamical processes in cells and organisms: (i) active motility and motility control and (ii) self-organized pattern formation. The unifying theme is the nonlinear dynamics of biological function and its robustness in the presence of strong fluctuations, structural variations, and external perturbations. We theoretically investigate motility control at the cellular scale, using cilia and flagella as ideal model system. Cilia and flagella are highly conserved slender cell appendages that exhibit spontaneous bending waves. This flagellar beat represents a prime example of a chemo-mechanical oscillator, which is driven by the collective dynamics of molecular motors inside the flagellar axoneme. We study the nonlinear dynamics of flagellar swimming, steering, and synchronization, which encompasses shape control of the flagellar beat by chemical signals and mechanical forces. Mechanical forces can synchronize collections of flagella to beat at a common frequency, despite active motor noise that tends to randomize flagellar synchrony. In Chapter 2, we present a new physical mechanism for flagellar synchronization by mechanical self-stabilization that applies to free-swimming flagellated cells. This new mechanism is independent of direct hydrodynamic interactions between flagella. Comparison with experimental data provided by experimental collaboration partners in the laboratory of J. Howard (Yale, New Haven) confirmed our new mechanism in the model organism of the unicellular green alga Chlamydomonas. Further, we characterize the beating flagellum as a noisy oscillator. Using a minimal model of collective motor dynamics, we argue that measured non-equilibrium fluctuations of the flagellar beat result from stochastic motor dynamics at the molecular scale. Noise and mechanical coupling are antagonists for flagellar synchronization. In addition to the control of the flagellar beat by mechanical forces, we study the control of the flagellar beat by chemical signals in the context of sperm chemotaxis. We characterize a fundamental paradigm for navigation in external concentration gradients that relies on active swimming along helical paths. In this helical chemotaxis, the direction of a spatial concentration gradient becomes encoded in the phase of an oscillatory chemical signal. Helical chemotaxis represents a distinct gradient-sensing strategy, which is different from bacterial chemotaxis. Helical chemotaxis is employed, for example, by sperm cells from marine invertebrates with external fertilization. We present a theory of sensorimotor control, which combines hydrodynamic simulations of chiral flagellar swimming with a dynamic regulation of flagellar beat shape in response to chemical signals perceived by the cell. Our theory is compared to three-dimensional tracking experiments of sperm chemotaxis performed by the laboratory of U. B. Kaupp (CAESAR, Bonn). In addition to motility control, we investigate in Chapter 3 self-organized pattern formation in two selected biological systems at the cell and organism scale, respectively. On the cellular scale, we present a minimal physical mechanism for the spontaneous self-assembly of periodic cytoskeletal patterns, as observed in myofibrils in striated muscle cells. This minimal mechanism relies on the interplay of a passive coarsening process of crosslinked actin clusters and active cytoskeletal forces. This mechanism of cytoskeletal pattern formation exemplifies how local interactions can generate large-scale spatial order in active systems. On the organism scale, we present an extension of Turing’s framework for self-organized pattern formation that is capable of a proportionate scaling of steady-state patterns with system size. This new mechanism does not require any pre-pattering clues and can restore proportional patterns in regeneration scenarios. We analytically derive the hierarchy of steady-state patterns and analyze their stability and basins of attraction. We demonstrate that this scaling mechanism is structurally robust. Applications to the growth and regeneration dynamics in flatworms are discussed (experiments by J. Rink, MPI CBG, Dresden).:1 Introduction 10 1.1 Overview of the thesis 10 1.2 What is biological physics? 12 1.3 Nonlinear dynamics and control 14 1.3.1 Mechanisms of cell motility 16 1.3.2 Self-organized pattern formation in cells and tissues 28 1.4 Fluctuations and biological robustness 34 1.4.1 Sources of fluctuations in biological systems 34 1.4.2 Example of stochastic dynamics: synchronization of noisy oscillators 36 1.4.3 Cellular navigation strategies reveal adaptation to noise 39 2 Selected publications: Cell motility and motility control 56 2.1 “Flagellar synchronization independent of hydrodynamic interactions” 56 2.2 “Cell body rocking is a dominant mechanism for flagellar synchronization” 57 2.3 “Active phase and amplitude fluctuations of the flagellar beat” 58 2.4 “Sperm navigation in 3D chemoattractant landscapes” 59 3 Selected publications: Self-organized pattern formation in cells and tissues 60 3.1 “Sarcomeric pattern formation by actin cluster coalescence” 60 3.2 “Scaling and regeneration of self-organized patterns” 61 4 Contribution of the author in collaborative publications 62 5 Eidesstattliche Versicherung 64 6 Appendix: Reprints of publications 66 / Das Thema der vorliegenden Habilitationsschrift in Theoretischer Biologischer Physik ist die nichtlineare Dynamik funktionaler biologischer Systeme und deren Robustheit gegenüber Fluktuationen und äußeren Störungen. Wir entwickeln hierzu theoretische Beschreibungen für zwei grundlegende biologische Prozesse: (i) die zell-autonome Kontrolle aktiver Bewegung, sowie (ii) selbstorganisierte Musterbildung in Zellen und Organismen. In Kapitel 2, untersuchen wir Bewegungskontrolle auf zellulärer Ebene am Modelsystem von Zilien und Geißeln. Spontane Biegewellen dieser dünnen Zellfortsätze ermöglichen es eukaryotischen Zellen, in einer Flüssigkeit zu schwimmen. Wir beschreiben einen neuen physikalischen Mechanismus für die Synchronisation zweier schlagender Geißeln, unabhängig von direkten hydrodynamischen Wechselwirkungen. Der Vergleich mit experimentellen Daten, zur Verfügung gestellt von unseren experimentellen Kooperationspartnern im Labor von J. Howard (Yale, New Haven), bestätigt diesen neuen Mechanismus im Modellorganismus der einzelligen Grünalge Chlamydomonas. Der Gegenspieler dieser Synchronisation durch mechanische Kopplung sind Fluktuationen. Wir bestimmen erstmals Nichtgleichgewichts-Fluktuationen des Geißel-Schlags direkt, wofür wir eine neue Analyse-Methode der Grenzzykel-Rekonstruktion entwickeln. Die von uns gemessenen Fluktuationen entstehen mutmaßlich durch die stochastische Dynamik molekularen Motoren im Innern der Geißeln, welche auch den Geißelschlag antreiben. Um die statistische Physik dieser Nichtgleichgewichts-Fluktuationen zu verstehen, entwickeln wir eine analytische Theorie der Fluktuationen in einem minimalen Modell kollektiver Motor-Dynamik. Zusätzlich zur Regulation des Geißelschlags durch mechanische Kräfte untersuchen wir dessen Regulation durch chemische Signale am Modell der Chemotaxis von Spermien-Zellen. Dabei charakterisieren wir einen grundlegenden Mechanismus für die Navigation in externen Konzentrationsgradienten. Dieser Mechanismus beruht auf dem aktiven Schwimmen entlang von Spiralbahnen, wodurch ein räumlicher Konzentrationsgradient in der Phase eines oszillierenden chemischen Signals kodiert wird. Dieser Chemotaxis-Mechanismus unterscheidet sich grundlegend vom bekannten Chemotaxis-Mechanismus von Bakterien. Wir entwickeln eine Theorie der senso-motorischen Steuerung des Geißelschlags während der Spermien-Chemotaxis. Vorhersagen dieser Theorie werden durch Experimente der Gruppe von U.B. Kaupp (CAESAR, Bonn) quantitativ bestätigt. In Kapitel 3, untersuchen wir selbstorganisierte Strukturbildung in zwei ausgewählten biologischen Systemen. Auf zellulärer Ebene schlagen wir einen einfachen physikalischen Mechanismus vor für die spontane Selbstorganisation von periodischen Zellskelett-Strukturen, wie sie sich z.B. in den Myofibrillen gestreifter Muskelzellen finden. Dieser Mechanismus zeigt exemplarisch auf, wie allein durch lokale Wechselwirkungen räumliche Ordnung auf größeren Längenskalen in einem Nichtgleichgewichtssystem entstehen kann. Auf der Ebene des Organismus stellen wir eine Erweiterung der Turingschen Theorie für selbstorganisierte Musterbildung vor. Wir beschreiben eine neue Klasse von Musterbildungssystemen, welche selbst-organisierte Muster erzeugt, die mit der Systemgröße skalieren. Dieser neue Mechanismus erfordert weder eine vorgegebene Kompartimentalisierung des Systems noch spezielle Randbedingungen. Insbesondere kann dieser Mechanismus proportionale Muster wiederherstellen, wenn Teile des Systems amputiert werden. Wir bestimmen analytisch die Hierarchie aller stationären Muster und analysieren deren Stabilität und Einzugsgebiete. Damit können wir zeigen, dass dieser Skalierungs-Mechanismus strukturell robust ist bezüglich Variationen von Parametern und sogar funktionalen Beziehungen zwischen dynamischen Variablen. Zusammen mit Kollaborationspartnern im Labor von J. Rink (MPI CBG, Dresden) diskutieren wir Anwendungen auf das Wachstum von Plattwürmern und deren Regeneration in Amputations-Experimenten.:1 Introduction 10 1.1 Overview of the thesis 10 1.2 What is biological physics? 12 1.3 Nonlinear dynamics and control 14 1.3.1 Mechanisms of cell motility 16 1.3.2 Self-organized pattern formation in cells and tissues 28 1.4 Fluctuations and biological robustness 34 1.4.1 Sources of fluctuations in biological systems 34 1.4.2 Example of stochastic dynamics: synchronization of noisy oscillators 36 1.4.3 Cellular navigation strategies reveal adaptation to noise 39 2 Selected publications: Cell motility and motility control 56 2.1 “Flagellar synchronization independent of hydrodynamic interactions” 56 2.2 “Cell body rocking is a dominant mechanism for flagellar synchronization” 57 2.3 “Active phase and amplitude fluctuations of the flagellar beat” 58 2.4 “Sperm navigation in 3D chemoattractant landscapes” 59 3 Selected publications: Self-organized pattern formation in cells and tissues 60 3.1 “Sarcomeric pattern formation by actin cluster coalescence” 60 3.2 “Scaling and regeneration of self-organized patterns” 61 4 Contribution of the author in collaborative publications 62 5 Eidesstattliche Versicherung 64 6 Appendix: Reprints of publications 66