@phdthesis{Mauri2014,
  author    = {Mauri, Marco},
  title     = {A model for sigma factor competition in bacterial cells},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-72098},
  school      = {Universit{\"a}t Potsdam},
  pages     = {167},
  year      = {2014},
  abstract  = {Bacteria respond to changing environmental conditions by switching the global pattern of expressed genes. In response to specific environmental stresses the cell activates several stress-specific molecules such as sigma factors. They reversibly bind the RNA polymerase to form the so-called holoenzyme and direct it towards the appropriate stress response genes. In exponentially growing E. coli cells, the majority of the transcriptional activity is carried out by the housekeeping sigma factor, while stress responses are often under the control of alternative sigma factors. Different sigma factors compete for binding to a limited pool of RNA polymerase (RNAP) core enzymes, providing a mechanism for cross talk between genes or gene classes via the sharing of expression machinery. To quantitatively analyze the contribution of sigma factor competition to global changes in gene expression, we develop a thermodynamic model that describes binding between sigma factors and core RNAP at equilibrium, transcription, non-specific binding to DNA and the modulation of the availability of the molecular components. Association of housekeeping sigma factor to RNAP is generally favored by its abundance and higher binding affinity to the core. In order to promote transcription by alternative sigma subunits, the bacterial cell modulates the transcriptional efficiency in a reversible manner through several strategies such as anti-sigma factors, 6S RNA and generally any kind of transcriptional regulators (e.g. activators or inhibitors). By shifting the outcome of sigma factor competition for the core, these modulators bias the transcriptional program of the cell. The model is validated by comparison with in vitro competition experiments, with which excellent agreement is found. We observe that transcription is affected via the modulation of the concentrations of the different types of holoenzymes, so saturated promoters are only weakly affected by sigma factor competition. However, in case of overlapping promoters or promoters recognized by two types of sigma factors, we find that even saturated promoters are strongly affected. Active transcription effectively lowers the affinity between the sigma factor driving it and the core RNAP, resulting in complex cross talk effects and raising the question of how their in vitro measure is relevant in the cell. We also estimate that sigma factor competition is not strongly affected by non-specific binding of core RNAPs, sigma factors, and holoenzymes to DNA. Finally, we analyze the role of increased core RNAP availability upon the shut-down of ribosomal RNA transcription during stringent response. We find that passive up-regulation of alternative sigma-dependent transcription is not only possible, but also displays hypersensitivity based on the sigma factor competition. Our theoretical analysis thus provides support for a significant role of passive control during that global switch of the gene expression program and gives new insights into RNAP partitioning in the cell.},
  language  = {en}
}
@phdthesis{Schwarz2004,
  author    = {Schwarz, Ulrich Sebastian},
  title     = {Forces and elasticity in cell adhesion},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-0001343},
  school      = {Universit{\"a}t Potsdam},
  year      = {2004},
  abstract  = {Das Verhalten adh{\"a}renter Zellen h{\"a}ngt stark von den chemischen, topographischen und mechanischen Eigenschaften ihrer Umgebung ab. Experimentelle Untersuchungen der letzten Jahre haben gezeigt, dass adh{\"a}rente Zellen aktiv die elastischen Eigenschaften ihrer Umgebung erkunden, indem sie an dieser ziehen. Der resultierende Kraftaufbau h{\"a}ngt von den elastischen Eigenschaften der Umgebung ab und wird an den Adh{\"a}sionskontakten in entsprechende biochemische Signale umgewandelt, die zellul{\"a}re Programme wie Wachstum, Differenzierung, programmierten Zelltod und Zellbewegung mitbestimmen. Im Allgemeinen sind Kr{\"a}fte wichtige Einflussgr{\"o}ßen in biologischen Systemen. Weitere Beispiele daf{\"u}r sind H{\"o}r- und Tastsinn, Wundheilung sowie die rollende Adh{\"a}sion von weißen Blutk{\"o}rperchen auf den W{\"a}nden der Blutgef{\"a}ße. In der Habilitationsschrift von Ulrich Schwarz werden mehrere theoretische Projekte vorgestellt, die die Rolle von Kr{\"a}ften und Elastizit{\"a}t in der Zelladh{\"a}sion untersuchen. (1) Es wurde eine neue Methode entwickelt, um die Kr{\"a}fte auszurechnen, die Zellen an den Kontaktpunkten auf mikro-strukturierte elastische Substrate aus{\"u}ben. Das Hauptergebnis ist, dass Zell-Matrix-Kontakte als Mechanosensoren funktionieren, an denen interne Kr{\"a}fte in Proteinaggregation umgewandelt werden. (2) Eine Ein-Schritt-Master-Gleichung, die die stochastische Dynamik von Adh{\"a}sionsclustern als Funktion von Clustergr{\"o}ße, R{\"u}ckbindungsrate und Kraft beschreibt, wurde sowohl analytisch als auch numerisch gel{\"o}st. Zudem wurde dieses Modell auf Zell-Matrix-Kontakte, dynamische Kraftspektroskopie sowie die rollende Adh{\"a}sion angewandt. (3) Im Rahmen der linearen Elastizit{\"a}tstheorie und mit Hilfe des Konzepts der Kraftdipole wurde ein Modell formuliert und gel{\"o}st, das die Positionierung und Orientierung von Zellen in weicher Umgebung vorhersagt. Diese Vorhersagen sind in guter {\"U}bereinstimmung mit zahlreichen experimentellen Beobachtungen f{\"u}r Fibroblasten auf elastischen Substraten und in Kollagen-Gelen.},
  language  = {en}
}
@phdthesis{Haluska2004,
  author    = {Haluska, Christopher K.},
  title     = {Interactions of functionalized vesicles in the presence of Europium (III) Chloride},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-2482},
  school      = {Universit{\"a}t Potsdam},
  year      = {2004},
  abstract  = {We incorporate amphiphilic receptors bearing ß-diketone functional units into large (LUV's) and giant unilamellar vesicles (GUV's). Electrolyte solutions containing di- and trivalent ions were used to induce inter-membrane interactions. Measurements performed with isothermal titration calorimetry (ITC) revealed that interaction between EuCl3 and ß-diketone receptors was characterized by a molar enthalpy 126 ± 5 kcal/mole and an equilibrium binding constant 26 ± 4 mM-1. The results indicate a molecular complex formed binding two ß-diketone receptors to one Eu3+ ion. Dynamic light scattering (DLS) was used to follow changes in LUV diameter indicated in an increase in vesicle size distribution of on average 20 \%. Optical microscopy was employed to visualize the inter-membrane interaction measured using DLS and ITC. Depending on membrane composition of the functionalized vesicles we found that local injections of micromolar EuCl¬3 induced membrane pore formation and membrane fusion. Our collection of results leads to the conclusion that formation of intra-molecular ligand receptor complexes leads to pore formation and inter-membrane complex formation leads to membrane fusion. Detailed characterization of the fusion process shows that irreversible opening of the fusion pore can be extrapolated to times below 50 µsec. We have found that formation of membrane bound ligand (Eu3+)-receptor complexes provides versatility to the function of vesicle membranes.},
  subject      = {Biophysik},
  language  = {de}
}
@phdthesis{Erdmann2005,
  author    = {Erdmann, Thorsten},
  title     = {Stochastic dynamics of adhesion clusters under force},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-5564},
  school      = {Universit{\"a}t Potsdam},
  year      = {2005},
  abstract  = {Adhesion of biological cells to their environment is mediated by two-dimensional clusters of specific adhesion molecules which are assembled in the plasma membrane of the cells. Due to the activity of the cells or external influences, these adhesion sites are usually subject to physical forces. In recent years, the influence of such forces on the stability of cellular adhesion clusters was increasingly investigated. In particular, experimental methods that were originally designed for the investigation of single bond rupture under force have been applied to investigate the rupture of adhesion clusters. The transition from single to multiple bonds, however, is not trivial and requires theoretical modelling. Rupture of biological adhesion molecules is a thermally activated, stochastic process. In this work, a stochastic model for the rupture and rebinding dynamics of clusters of parallel adhesion molecules under force is presented. In particular, the influence of (i) a constant force as it may be assumed for cellular adhesion clusters is investigated and (ii) the influence of a linearly increasing force as commonly used in experiments is considered. Special attention is paid to the force-mediated cooperativity of parallel adhesion bonds. Finally, the influence of a finite distance between receptors and ligands on the binding dynamics is investigated. Thereby, the distance can be bridged by polymeric linker molecules which tether the ligands to a substrate.},
  subject      = {Biophysik},
  language  = {en}
}
@phdthesis{Lepro2021,
  author    = {Lepro, Valentino},
  title     = {Experimental and theoretical study on amoeboid cell-cargo active motion},
  doi       = {10.25932/publishup-49089},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-490890},
  school      = {Universit{\"a}t Potsdam},
  pages     = {xx, 114},
  year      = {2021},
  abstract  = {As society paves its way towards device miniaturization and precision medicine, micro-scale actuation and guided transport become increasingly prominent research fields, with high potential impact in both technological and clinical contexts. In order to accomplish directed motion of micron-sized objects, as biosensors and drug-releasing microparticles, towards specific target sites, a promising strategy is the use of living cells as smart biochemically-powered carriers, building the so-called bio-hybrid systems. Inspired by leukocytes, native cells of living organisms efficiently migrating to critical targets as tumor tissue, an emerging concept is to exploit the amoeboid crawling motility of such cells as mean of transport for drug delivery applications. In the research work described in this thesis, I synergistically applied experimental, computational and theoretical modeling approaches to investigate the behaviour and transport mechanism of a novel kind of bio-hybrid system for active transport at the micro-scale, referred to as cellular truck. This system consists of an amoeboid crawling cell, the carrier, attached to a microparticle, the cargo, which may ideally be drug-loaded for specific therapeutic treatments. For the purposes of experimental investigation, I employed the amoeba Dictyostelium discoideum as crawling cellular carrier, being a renowned model organism for leukocyte migration and, in general, for eukaryotic cell motility. The performed experiments revealed a complex recurrent cell-cargo relative motion, together with an intermittent motility of the cellular truck as a whole. The evidence suggests the presence of cargoes on amoeboid cells to act as mechanical stimulus leading cell polarization, thus promoting cell motility and giving rise to the observed intermittent dynamics of the truck. Particularly, bursts in cytoskeletal polarity along the cell-cargo axis have been found to occur in time with a rate dependent on cargo geometrical features, as particle diameter. Overall, the collected experimental evidence pointed out a pivotal role of cell-cargo interactions in the emergent cellular truck motion dynamics. Especially, they can determine the transport capabilities of amoeboid cells, as the cargo size significantly impacts the cytoskeletal activity and repolarization dynamics along the cell-cargo axis, the latter responsible for truck displacement and reorientation. Furthermore, I developed a modeling framework, built upon the experimental evidence on cellular truck behaviour, that connects the relative dynamics and interactions arising at the truck scale with the actual particle transport dynamics. In fact, numerical simulations of the proposed model successfully reproduced the phenomenology of the cell-cargo system, while enabling the prediction of the transport properties of cellular trucks over larger spatial and temporal scales. The theoretical analysis provided a deeper understanding of the role of cell-cargo interaction on mass transport, unveiling in particular how the long-time transport efficiency is governed by the interplay between the persistence time of cell polarity and time scales of the relative dynamics stemming from cell-cargo interaction. Interestingly, the model predicts the existence of an optimal cargo size, enhancing the diffusivity of cellular trucks; this is in line with previous independent experimental data, which appeared rather counterintuitive and had no explanation prior to this study. In conclusion, my research work shed light on the importance of cargo-carrier interactions in the context of crawling cell-mediated particle transport, and provides a prototypical, multifaceted framework for the analysis and modelling of such complex bio-hybrid systems and their perspective optimization.},
  language  = {en}
}
@phdthesis{Dunlop2015,
  author    = {Dunlop, John William Chapman},
  title     = {The physics of shape changes in biology},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-96554},
  school      = {Universit{\"a}t Potsdam},
  pages     = {vii, 202},
  year      = {2015},
  abstract  = {Biological materials, in addition to having remarkable physical properties, can also change shape and volume. These shape and volume changes allow organisms to form new tissue during growth and morphogenesis, as well as to repair and remodel old tissues. In addition shape or volume changes in an existing tissue can lead to useful motion or force generation (actuation) that may even still function in the dead organism, such as in the well known example of the hygroscopic opening or closing behaviour of the pine cone. Both growth and actuation of tissues are mediated, in addition to biochemical factors, by the physical constraints of the surrounding environment and the architecture of the underlying tissue. This habilitation thesis describes biophysical studies carried out over the past years on growth and swelling mediated shape changes in biological systems. These studies use a combination of theoretical and experimental tools to attempt to elucidate the physical mechanisms governing geometry controlled tissue growth and geometry constrained tissue swelling. It is hoped that in addition to helping understand fundamental processes of growth and morphogenesis, ideas stemming from such studies can also be used to design new materials for medicine and robotics.},
  language  = {en}
}
@phdthesis{RodriguezLoureiro2018,
  author    = {Rodriguez Loureiro, Ignacio},
  title     = {Structural characterization of single and interacting soft interfaces displaying brushes of synthetic or biomolecular polymers},
  doi       = {10.25932/publishup-42367},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-423675},
  school      = {Universit{\"a}t Potsdam},
  pages     = {132},
  year      = {2018},
  abstract  = {The interaction between surfaces displaying end-grafted hydrophilic polymer brushes plays important roles in biology and in many wet-technological applications. The outer surfaces of Gram-negative bacteria, for example, are composed of lipopolysaccharide (LPS) molecules exposing oligo- and polysaccharides to the aqueous environment. This unique, structurally complex biological interface is of great scientific interest as it mediates the interaction of bacteria with neighboring bacteria in colonies and biofilms. The interaction between polymer-decorated surfaces is generally coupled to the distance-dependent conformation of the polymer chains. Therefore, structural insight into the interacting surfaces is a prerequisite to understand the interaction characteristics as well as the underlying physical mechanisms. This problem has been addressed by theory, but accurate experimental data on polymer conformations under confinement are rare, because obtaining perturbation-free structural insight into buried soft interfaces is inherently difficult. In this thesis, lipid membrane surfaces decorated with hydrophilic polymers of technological and biological relevance are investigated under controlled interaction conditions, i.e., at defined surface separations. For this purpose, dedicated sample architectures and experimental tools are developed. Via ellipsometry and neutron reflectometry pressure-distance curves and distance-dependent polymer conformations in terms of brush compression and reciprocative interpenetration are determined. Additional element-specific structural insight into the end-point distribution of interacting brushes is obtained by standing-wave x-ray fluorescence (SWXF). The methodology is first established for poly[ethylene glycol] (PEG) brushes of defined length and grafting density. For this system, neutron reflectometry revealed pronounced brush interpenetration, which is not captured in common brush theories and therefore motivates rigorous simulation-based treatments. In the second step the same approach is applied to realistic mimics of the outer surfaces of Gram-negative bacteria: monolayers of wild type LPSs extracted from E. Coli O55:B5 displaying strain-specific O-side chains. The neutron reflectometry experiments yield unprecedented structural insight into bacterial interactions, which are of great relevance for the properties of biofilms.},
  language  = {en}
}