No description available.

O objetivo deste trabalho foi avaliar a posição da suspensão de carcaças durante o período de resfriamento, no primeiro experimento lados alternados de dez animais Nelores machos castrados, foram suspensos pelo método tradicional (Tendão de Aquiles) ou dispostos horizontalmente em pallets, no segundo experimento lados alternados de 16 animais machos castrados e 16 fêmeas foram suspensos pelo método tradicional (Tendão de Aquiles) ou pelo músculo Carpo Radial. Amostras do músculo Longissimus dorsi na 12ª costela foram coletadas de todos os lados (42 lados esquerdos e 42 lados direitos) após o período de 24 horas de resfriamento, estas amostras foram embaladas a vácuo e maturadas por sete dias antes de serem congeladas e armazenadas até a realização das analises de força de cisalhamento, perdas de água por cocção e índice de fragmentação miofibrilar (MFI). Para a primeira experiência nenhuma diferença foi observada para espessura de gordura subcutânea, perdas de água por cocção, força de cisalhamento e MFI.Na segunda experiência não houve diferença para espessura de gordura entre os tratamentos, mas as fêmeas apresentavam maior espessura que os machos. Para perdas de água por cocção e força de cisalhamento não houve diferença, mas observando o MFI existe diferença entre os machos e fêmeas e também entre os métodos de pendura. A média de MFI para o tratamento de suspensão pelo Carpo Radial foi maior do que a suspensão pelo tendão de Aquiles. / The objective of this work was to evaluate the carcass hanging position during the chilling period in which 1st experiment: alternate sides of ten Nellore steers were hang either by the traditional way (Achilles tendon) or placed horizontally over pallets or 2nd experiment: alternate sides of 16 Nellore steers and 16 Nellore heifers were hang either by the Achilles tendon or by the Carpus radial muscle of the forequarter. Longissimus dorsi muscle samples at the 12th rib level were removed from all sides (42 left and 42 right sides) after a 24 hr chilling period, vacuum packaged and aged for 7 days before being frozen and kept for future analysis of shear force, cooking losses and Myofibril fragmentation index (MFI). For the first experiment no differences were observed for fat thickness, cooking losses, shear force and MFI. In the second experiment there was not differences for fat thickness between treatments but heifers showed a thicker fat layer than steers. For cooking losses and shear force there was not differences although for the MFI and hanging position between heifers and steers were observed. The MFI average of the treatment hang by the Carpus radial muscle were higher than the treatment hang by the Achilles tendon.

Made available in DSpace on 2015-04-22T22:17:26Z (GMT). No. of bitstreams: 1 daniel wolinger.pdf: 5533005 bytes, checksum: 52d8c2a65d3daac6f6a55be4012bcb37 (MD5) Previous issue date: 2010-12-06 / Fishing is an important extractive activity in the Amazon, and offering nutritional source income, leisure and food base of a large proportion of its population. His organic constitution, as well as other food matrices, under certain preparation conditions, such as baking, suffers physical and chemical changes, which may give rise to secondary products. The aim of this study was to analyze the formation of nitrates and nitrites (nitrosating compounds), which are important precursors of nitrous compounds from protein myofibrillar degradation caused by application of heat in samples of sardine (Triportheus angulatus) for 30 to 60 minutes. Being a methodology quick, simple and show a sensitive mechanism able to separate the components of the sample, we used the one-dimensional discontinuous SDS-PAGE under the following conditions: 120 minutes, 100 V and 25 mA. With the same samples were quantified the total proteins by the biuret method, determined by the methodology of the MFI measured turbidity and nitrates and nitrites by spectrophotometry. Research suggests that the reaction of nitrosating compounds (nitrates and nitrites) and nitronisáveis (proteins, amino acids and others) originate secondary substances, nitrous compounds. The zymogram revealed degradation of myofibrils in structures with molecular weight between 10 and 20 KDa. Protein content showed a decrease in the amount of protein in the samples roasted for 30 and 60 minutes from about 12.5%, and the determination of MFI was 42.93. The average nitrite in fresh samples, baked 60 minutes and 30 was 0.0001% (m / m), 0.0063% (w / w) and 0.0030% (w / w) respectively. The average nitrate found in fresh samples, baked 30 and 60 was 0.0020% (m / m), 0.00001% (m / m) and 0.00001% (m / m) respectively, both below 0.02% to 0.1% nitrite and nitrate as an upper limit set by law. Their absence or insignificant formation allows us to conclude that there is no relationship between protein degradation as evidenced by the change of myofibrillar zymogram, the MFI and the decrease of total proteins with a possible formation of secondary substances from nitrates and nitrites. / A pesca é uma importante atividade extrativista na Amazônia, sendo fonte nutricional de renda e lazer de grande parte da população. Sua constituição orgânica, assim como de outras matrizes alimentares, sob determinadas condições de preparo sofre alterações físicas e químicas. Pesquisas indicam que reações entre compostos nitrosantes (nitratos e nitritos) e nitronisáveis (proteínas, aminoácidos entre outros) originem substâncias secundárias, como os compostos nitrosos. O objetivo deste trabalho foi quantificar a formação de nitratos e nitritos (compostos nitrosantes), importantes precursores de compostos nitrosos, a partir da degradação protéica miofibrilar por aplicação de calor através de assamento de amostras de sardinha (Triportheus angulatus) durante 30 e 60 minutos com carvão vegetal. Para determinar a perda protéica, foi quantificado o MFI pela metodologia da turbidez. Por apresentar uma capacidade de separação mais eficiente de proteínas e de outros compostos, além de ser uma metodologia de simples execução, relativamente rápida, podendo ser aplicada em varias amostras, também foi utilizado SDS- PAGE descontinua monodimensional para demonstrar perda protéica. O zimograma das miofibrilas evidenciou degradação em estruturas com peso molecular entre 10 e 20 KDa. A dosagem de proteínas mostrou diminuição da quantidade de proteínas nas amostras assadas por 30 e 60 minutos de aproximadamente 12,5%, e a determinação do MFI foi de 42,93. A média de nitritos nas amostras in natura, assadas 30 e 60 minutos foi de 0,0001% (m/m), 0,0063% (m/m) e 0,0030% (m/m) respectivamente. A média de nitratos encontrados nas amostras in natura, assadas 30 e 60 foi de 0,0020% (m/m), 0,00001% (m/m) e 0,00001%(m/m) respectivamente, ambos abaixo dos 0,02% de nitrito e 0,1% de nitrato definidos como limite máximo pela legislação. A sua baixa quantificação tanto in natura, quanto em assado por 30 e 60 minutos permite concluir a existência de uma relação entre a degradação protéica evidenciada pela alteração do zimograma miofibrilar, da quantificação do MFI e das proteínas totais.

O objetivo deste trabalho foi avaliar a posição da suspensão de carcaças durante o período de resfriamento, no primeiro experimento lados alternados de dez animais Nelores machos castrados, foram suspensos pelo método tradicional (Tendão de Aquiles) ou dispostos horizontalmente em pallets, no segundo experimento lados alternados de 16 animais machos castrados e 16 fêmeas foram suspensos pelo método tradicional (Tendão de Aquiles) ou pelo músculo Carpo Radial. Amostras do músculo Longissimus dorsi na 12ª costela foram coletadas de todos os lados (42 lados esquerdos e 42 lados direitos) após o período de 24 horas de resfriamento, estas amostras foram embaladas a vácuo e maturadas por sete dias antes de serem congeladas e armazenadas até a realização das analises de força de cisalhamento, perdas de água por cocção e índice de fragmentação miofibrilar (MFI). Para a primeira experiência nenhuma diferença foi observada para espessura de gordura subcutânea, perdas de água por cocção, força de cisalhamento e MFI.Na segunda experiência não houve diferença para espessura de gordura entre os tratamentos, mas as fêmeas apresentavam maior espessura que os machos. Para perdas de água por cocção e força de cisalhamento não houve diferença, mas observando o MFI existe diferença entre os machos e fêmeas e também entre os métodos de pendura. A média de MFI para o tratamento de suspensão pelo Carpo Radial foi maior do que a suspensão pelo tendão de Aquiles. / The objective of this work was to evaluate the carcass hanging position during the chilling period in which 1st experiment: alternate sides of ten Nellore steers were hang either by the traditional way (Achilles tendon) or placed horizontally over pallets or 2nd experiment: alternate sides of 16 Nellore steers and 16 Nellore heifers were hang either by the Achilles tendon or by the Carpus radial muscle of the forequarter. Longissimus dorsi muscle samples at the 12th rib level were removed from all sides (42 left and 42 right sides) after a 24 hr chilling period, vacuum packaged and aged for 7 days before being frozen and kept for future analysis of shear force, cooking losses and Myofibril fragmentation index (MFI). For the first experiment no differences were observed for fat thickness, cooking losses, shear force and MFI. In the second experiment there was not differences for fat thickness between treatments but heifers showed a thicker fat layer than steers. For cooking losses and shear force there was not differences although for the MFI and hanging position between heifers and steers were observed. The MFI average of the treatment hang by the Carpus radial muscle were higher than the treatment hang by the Achilles tendon.

Although the long-term therapeutic benefits of exercise are indisputable, contractile activity may induce divergent adaptations in insulin-resistant vs. insulin-sensitive skeletal muscle. The purpose of this study was to elucidate if the anabolic response following resistance exercise (RE) is altered in myocellular sub-fractions in the face of insulin resistance. Lean (Fa/?) and obese (fa/fa) Zucker rats were assigned to sedentary and RE groups and engaged in either cage rest or four lower-body RE sessions over an 8-d period. Despite obese Zucker rats having significantly smaller hindlimb muscles when compared to age-matched lean rats, basal 24-h fractional synthesis rates (FSR) of mixed protein pools were near normal in distally located muscle groups (gastrocnemius, plantaris, and soleus) and even augmented in those located more proximally (P<0.05; quadriceps). Although 2 x 2 ANOVA indicated a significant main effect of phenotype on mixed FSR in gastrocnemius and soleus (P < 0.05), phenotypic differences were partially accounted for by an exercise effect in the lean phenotype. Interestingly, obese rats exhibited a significant suppression of myofibrillar FSR compared to their lean counterparts (P<0.05; gastrocnemius), while synthesis rates of mitochondrial and cytosolic proteins were normal (gastrocnemius and quadriceps), suggesting a mechanism whereby translation of specific mRNA pools encoding for metabolic enzymes may be favored over other transcripts (e.g., contractile proteins) to cope with nutrient excess in the insulin-resistant state. Immunoblotting of the cytosolic fraction in gastrocnemius muscle indicated an augmented phosporylation of eIF4EBP1 (+ 9%) and p70s6k (+85%) in obese vs. lean rats, but a more potent baseline inhibition of polypeptide-chain elongation as evidenced by an increased phospho/total ratio of eEF2 (+78%) in the obese phenotype. Resistance exercise did not improve synthesis rates of myofibrillar, cytosolic, or mitochondrial proteins to the same extent in obese vs. lean rats, suggesting a desensitization to contractile-induced anabolic stimuli in the insulin-resistant state. We conclude that insulin resistance has diverse effects on protein metabolism, which may vary between muscle groups depending on fiber type distribution, location along the proximodistal body axis, and myocellular sub-fraction, and may blunt the anabolic response to voluntary resistance exercise.

No description available.

Three novel mutations (G159D, L29Q and E59D/D75Y) in cardiac troponin C (CTnC) associate their clinical outcomes with a given cardiomyopathy. Current paradigms propose that sarcomeric mutations associated with dilated cardiomyopathy (DCM) decrease the myofilament calcium sensitivity while those associated with hypertrophic (HCM) cardiomyopathy increase it. Therefore, we incorporated the mutant CTnCs into skinned cardiac muscle in order to determine if their effects on the calcium regulation of tension and ATPase activity coincide with the current paradigms and phenotypic outcomes. This required the development of new calculator programs to solve complex ionic equilibria to more accurately buffer and expand the free calcium range of our test solutions. In accordance with the DCM paradigms, our result show that G159D and E59D/D75Y CTnC decrease the myofilament calcium sensitivity and force generating capabilities which would likely increase the rate of muscle relaxation and weaken the contractile force of the myocardium. Alternatively, the lack of myofilament change from L29Q CTnC (associated with HCM) may explain why the only proband is seemingly unaffected. Notably, the changes in the calcium sensitivity of tension (in fibers) do not necessarily occur in the isolated CTnC and vice versa. These counter-intuitive findings are justified through a transition in calcium affinity occurring at the level of cardiac troponin (CTn) and higher, implying that the true effects of these mutations become apparent as the hierarchal level of the myofilament increases. Despite these limitations, the regulated thin filament (RTF) retains its role as the calcium regulatory unit and best indicates a mutation's ability to sensitize (+) or desensitize (-) the muscle to calcium. Since multiple forms of cardiomyopathies exist, the identification of new drugs that sensitize (+) or desensitize (-) the calcium sensitivity could potentially reverse (+ or -) these aberrant changes in myofilament sensitivity. Therefore, we have developed an RTF mediated High Throughput Screening assay to identify compounds in libraries of molecules that can specifically modulate the calcium sensitivity of cardiac contraction. The knowledge gained from these studies will help us and others to uncover new pharmacological agents for the investigation and treatments of cardiomyopathies, hypertension and other forms of cardiovascular diseases.

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