For biomedical electronics the compatibility to the biological environment should be well-considered. Therefore this paper evaluates dispensed carbon nanotubes (CNT's) on polyimide (PI) foil for conductive tracks and electrodes for flexible, biomedical applications. A CNT based ink is investigated regarding biocompatibility, flexibility, conductivity and suitability for electrode materials with contact to artificial body fluids. The testing methods comprise bending tests with resistance monitoring, adhesion tests and the utilization of dynamic fluidic and electrical load on dispensed structures. The CNT ink showed good bending properties up to 2653 cycles with an average sheet resistance of 32.5 Ohm/sq. A demonstration of biocompatibility using the adherent cell line HFFF2 resulted negatively. No delamination or dissolving effects occurred during exposure to 0.9 % sodium chloride solution.

The soil response in triaxial compression tests, that are commonly treated as element tests, is known to be inhomogeneous. Several studies have revealed the localisation of deformation throughout the whole specimen by digital image correlation techniques on X-ray tomographies. The fabric of a soil specimen has so far only been studied on complete specimens as a bulk measurement or in chosen subsets. In this contribution, we present a study on the spatial and temporal distribution of the fabric throughout one Hostun sand sample in triaxial compression. Therefore, we calibrated the minimum representative element size first for three chosen fabric variables considering three different criteria. By distributing the elements in a regular grid over the specimen, we are able to clearly identify the onset of the localisation in terms of void ratio, coordination number and contact fabric anisotropy. Spatially and temporally the contact fabric variables precede the void ratio changes as they are much more sensitive to small changes.

The majority of constitutive models, that are used nowadays to describe the behaviour of granular materials such as sands, are continuum models based on phenomenological approaches. In order to describe some of the phenomena occurring on the macroscopic scale, e.g., the abrupt change of stiffness due to a load reversal, constitutive models use phenomenological state variables (e.g., the inter-granular strain concept for hypoplasticity). These often lack a clear physical meaning. The mechanisms that control the macroscopic behaviour must be sought at the grain-scale with the interactions of individual particles playing the key-role. To access that scale and describe the fabric of granular assemblies, x-ray μ-computed tomography is used in this thesis for full-field measurements during monotonic and cyclic experiments. This non-destructive technique allows to acquire 3D images at various stages of the loading and thus, a tracking of the evolution of the fabric. The spatial resolution of such tomographies is limited as the specimen has to be mechanically representative and at the same time sufficiently small to identify individual grains in the images. Different image analysis techniques can be used to extract information on the fabric of the granular material, but they all lack a thorough metrological characterisation, especially regarding the limited spatial resolution. Therefore, it was necessary to study the different techniques and determine their uncertainties before running the experiments and evaluating the tomographies. Artificial as well as high resolution images serve as the basis of the metrological analysis which showed that the standard approaches for the analysis of contact orientations, implemented in most commercial software, strongly suffer in accuracy and often introduce huge artefacts. New techniques to refine these measures are proposed and validated on the same images. Monotonic triaxial compression tests on two different sands are studied regarding the localisation of deformation in terms of the contact fabric. The complete fabric tensor is determined inside and outside of the developing shear band throughout the experiment. Its evolution is expressed by the anisotropy and related to the macroscopic response. The specimen appears to behave homogeneously in the different zones until the onset of the localisation at which the fabric diverges. Outside of the shear band it stays relatively constant whereas it seems directly related to the stress ratio inside the shear band. The anisotropy captures the characteristic evolution of the stress response, such as peak states and softening. A series of triaxial compression tests with load reversals has been conducted on specimens consisting of sand grains and glass beads. To capture the fabric response to the cycles, tomographies have been acquired before and after unloading and after reloading. As opposed to numerical simulations, no large changes of the fabric during the load cycles could be observed. Qualitatively, the fabric changes similar to the numerical simulations: the anisotropy decreases upon unloading and increases upon reloading. The incremental response to each reversal is compared to the numerical simulations and the evolution of the inter-granular strain tensor for similar conditions. The latter is determined by a simplified element test with the aim of possibly relating this phenomenological variable to a truly structural one. The comparison of the evolution of the fabric and the inter-granular strain, however, showed major differences, based on which such a relation is not possible. The fabric evolves at a slower rate than the state variable and continues to evolve even throughout monotonic loading situations. / Der Großteil der Stoffmodelle, die heutzutage zur Beschreibung des Verhaltens von granularen Materialien wie Sanden verwendet werden, sind Modelle im Kontinuum, die auf phänomenologischen Ansätzen basieren. Diese Stoffmodelle nutzen oft phänomenologische Zustandsvariablen (z.B. die intergranulare Dehnung in der Hypoplastizität), um Phänomene, die auf makroskopischer Ebene beobachtet werden können, wie z.B. ein abrupter Wechsel der Steifigkeit bei Lastumkehr, zu beschreiben. Der Großteil dieser Zustandsvariablen ist aus theoretischen Konzepten hervorgegangen, die bisher noch nicht auf experimentelle Grundlagen gestellt werden konnten. Die Mechanismen, die das makroskopische Verhalten und die Phänomene auf dieser Ebene kontrollieren, müssen auf der Kornskala gesucht werden, da die Interaktionen von individuellen Körnern die Schlüsselrolle spielen. Um die Struktur von Granulaten auf dieser Skala beschreiben zu können, kommt die Röntgen Computertomographie in dieser Arbeit zum Einsatz. Diese erlaubt es 3D Bilder von Proben während einer makroskopischen Belastung zu erstellen und somit Strukturänderungen zu verfolgen. Hierbei ist es wichtig, zu beachten, dass die räumliche Auflösung der Tomographien limitiert ist, da mechanisch repräsentative Proben untersucht werden sollen. Mit verschiedenen Bildbearbeitungstools können aus diesen Bildern Informationen zur Struktur der Proben gewonnen werden. Aufgrund der limitierten Auflösung und unzureichenden, bisher durchgeführten Studien war es notwendig, diese Tools auf ihre Genauigkeit zu untersuchen. Mit Hilfe von synthetischen Bildern und hochauflösenden Nano-Tomographien, die als Basis für diese Analyse dienten, konnte festgestellt werden, dass Standardverfahren, die auch in kommerziellen Programmen implementiert sind, eine unzureichende Genauigkeit aufweisen. Aus diesem Grund wurden fortgeschrittene Verfahren hinsichtlich ihrer Genauigkeit und Verwendbarkeit untersucht und Verfeinerungen der Standardverfahren vorgeschlagen. Es konnte gezeigt werden, dass diese Verbesserungen eine wesentlich höhere Genauigkeit hinsichtlich der zu bestimmenden Strukturgrößen aufweisen. Mit diesen optimierten Verfahren wurde die Lokalisierung von Verformungen in monotonen Triaxialversuchen an zwei verschiedenen Sanden untersucht. Dazu wurde die Struktur innerhalb und außerhalb eines sich entwickelnden Scherbandes bestimmt und über einen Strukturtensor dargestellt. Die Proben verhalten sich relativ homogen bis zum Anfang der Lokalisierung. Danach wird die Struktur innerhalb des Scherbandes zunehmend anisotroper, indem sich die Kontakte immer weiter in Richtung der größten Hauptspannung ausrichten. Außerhalb des Scherbandes verändert sie sich kaum. Die Anisotropie des Strukturtensors bildet die Entwicklung des Spannungsdeviators dabei sehr gut ab. Um die abrupte Änderung der Steifigkeit bei Lastumkehr zu untersuchen, wurden Experimente an Sand- und Glaskugelproben durchgeführt, bei denen die Lastrichtung zu unterschiedlichen Zuständen umgekehrt wurde. Dabei wurden Tomographien von der Probe inbesondere vor und nach der Entlastung sowie nach der Wiederbelastung erstellt. Im Gegensatz zu Untersuchungen mit der DEM, entwickelt sich die Struktur in diesen Experimenten nur sehr gering. Qualitativ sind die Änderungen aber ähnlich mit denen aus den numerischen Simulationen: die Anisotropie verringert sich bei Ent- und vergrößert sich bei Wiederbelastung. Die inkrementelle Änderung der Anisotropie bei Lastumkehr wurde mit den Ergebnissen aus den numerischen Simulationen sowie der Entwicklung der intergranularen Dehnung verglichen. Mit dem Ziel dieses phänomenologische Konzept auf experimentelle Grundlagen zu stellen, wurde die intergranulare Dehnung in einer Simulation bei ähnlichen Bedingungen ermittelt. Eine experimentelle Erklärung dieses Konzeptes ist zumindest mit der Kontaktstruktur nicht möglich, da sich beide Variablen unterschiedlich entwickeln. Die Struktur entwickelt sich langsamer als die Zustandsvariable und weit über die Lastumkehr hinaus. / La majorité des modèles constitutifs, utilisés aujourd’hui pour décrire le comportement de matériaux granulaires, sont des modèles de continuum basés sur des approches phénoménologiques. Afin de décrire certains des phénomènes qui se produisent à l’échelle macroscopique, par exemple: le changement brusque de rigidité à une inversion de charge, les modèles constitutifs utilisent des variables d’état phénoménologiques (par exemple: le concept de déformation intergranulaire pour l’hypoplasticité). Ces modèles manquent souvent d’une signification physique. Les mécanismes qui contrôlent le comportement macroscopique doivent être étudiés à l’échelle du grain, car les interactions des particules jouent un rôle essentiel. Pour accéder à cette échelle et décrire la structure des assemblages granulaires, la tomographie par rayons X est utilisée dans ces travaux de thèse. La résolution spatiale de telles tomographies est limitée car le spécimen doit avoir une taille mécaniquement représentative et en même temps doit être suffisamment petit pour identifier les grains individuels dans les images. Différentes techniques d’analyse d’images peuvent être utilisées pour extraire des informations sur la structure du matérial granulaire, mais elles manquent toutes d’une caractérisation métrologique approfondie.Donc, il était nécessaire d’étudier les différentes techniques et de déterminer leurs incertitudes. Les images artificielles ainsi que les images haute résolution servent de base à l’analyse métrologique, qui a montré que les approches standard pour l’analyse des orientations de contact, mises en œuvre dans la plupart des logiciels commerciaux, sont inexacts et entraînent souvent d’importants artefacts. De nouvelles techniques pour affiner ces mesures sont proposées et validées sur les mêmes images. Des essais de compression triaxiaux monotoniques sur deux sables différents sont étudiés en ce qui concerne la localisation de la déformation par rapport au structure de contact. Le tenseur de structure complet est déterminé à l’intérieur et à l’extérieur de la bande de cisaillement en développement tout au long de l’expérience. Son évolution est exprimée par l’anisotropie et liée à la réponse macroscopique. Le spécimen semble se comporter de manière homogène dans les différentes zones jusqu’au début de la localisation à laquelle le tissu diverge. En dehors de la bande de cisaillement, il reste relativement constant alors qu’il semble directement lié au taux de contrainte à l’intérieur de la bande de cisaillement. L’anisotropie capture l’évolution caractéristique de la réponse a la contrainte, telle que les états de pic et le ramollissement. Une série d’essais de compression triaxiale avec inversion de charge a été réalisée sur des échantillons constitués de grains de sable et de billes de verre. Pour capturer la réponse de la structure aux cycles de charge, des tomographies ont été acquises avant et après le déchargement et après le rechargement. Contrairement aux simulations numériques, aucun changement important du tissu au cours de ces cycles n’a pas pu être observé. Qualitativement, les changements de structure ressemblent à ceux des simulations numériques: l’anisotropie diminue au déchargement et augmente au rechargement. La réponse incrémentale à chaque inversion est comparée aux simulations numériques et à l’évolution du tenseur de déformation intergranulaire sous des conditions similaires. La déformation intergranulaire est déterminée par un test élémentaire simplifié dans le but de relier éventuellement cette variable phénoménologique à une variable véritablement structurelle. La comparaison de l’évolution du tissu et de la déformation intergranulaire a toutefois révélé des différences majeures, sur la base desquelles une telle relation n’est pas possible. La structure évolue à un taux plus lent que la variable d’état et continue d’évoluer même dans les situations de chargement monotone.

Proteins have an indispensable role in the cell. They carry out a wide variety of structural, catalytic and signaling functions in all known biological systems. To perform their biological functions, proteins establish interactions with other bioorganic molecules including other proteins. Therefore, protein-protein interactions is one of the central topics in molecular biology. My thesis is devoted to three different topics in the field of protein-protein interactions. The first one focuses on solvent contribution to protein interfaces as it is an important component of protein complexes. The second topic discloses the structural and functional potential of fluorine's unique properties, which are attractive for protein design and engineering not feasible within the scope of canonical amino acids. The last part of this thesis is a study of the impact of charged amino acid residues within the hydrophobic interface of a coiled-coil system, which is one of the well-established model systems for protein-protein interactions studies. I. The majority of proteins interact in vivo in solution, thus studies of solvent impact on protein-protein interactions could be crucial for understanding many processes in the cell. However, though solvent is known to be very important for protein-protein interactions in terms of structure, dynamics and energetics, its effects are often disregarded in computational studies because a detailed solvent description requires complex and computationally demanding approaches. As a consequence, many protein residues, which establish water-mediated interactions, are neither considered in an interface definition. In the previous work carried out in our group the protein interfaces database (SCOWLP) has been developed. This database takes into account interfacial solvent and based on this classifies all interfacial protein residues of the PDB into three classes based on their interacting properties: dry (direct interaction), dual (direct and water-mediated interactions), and wet spots (residues interacting only through one water molecule). To define an interaction SCOWLP considers a donor–acceptor distance for hydrogen bonds of 3.2 Å, for salt bridges of 4 Å, and for van der Waals contacts the sum of the van der Waals radii of the interacting atoms. In previous studies of the group, statistical analysis of a non-redundant protein structure dataset showed that 40.1% of the interfacial residues participate in water-mediated interactions, and that 14.5% of the total residues in interfaces are wet spots. Moreover, wet spots have been shown to display similar characteristics to residues contacting water molecules in cores or cavities of proteins. The goals of this part of the thesis were: 1. to characterize the impact of solvent in protein-protein interactions 2. to elucidate possible effects of solvent inclusion into the correlated mutations approach for protein contacts prediction To study solvent impact on protein interfaces a molecular dynamics (MD) approach has been used. This part of the work is elaborated in section 2.1 of this thesis. We have characterized properties of water-mediated protein interactions at residue and solvent level. For this purpose, an MD analysis of 17 representative complexes from SH3 and immunoglobulin protein families has been performed. We have shown that the interfacial residues interacting through a single water molecule (wet spots) are energetically and dynamically very similar to other interfacial residues. At the same time, water molecules mediating protein interactions have been found to be significantly less mobile than surface solvent in terms of residence time. Calculated free energies indicate that these water molecules should significantly affect formation and stability of a protein-protein complex. The results obtained in this part of the work also suggest that water molecules in protein interfaces contribute to the conservation of protein interactions by allowing more sequence variability in the interacting partners, which has important implications for the use of the correlated mutations concept in protein interactions studies. This concept is based on the assumption that interacting protein residues co-evolve, so that a mutation in one of the interacting counterparts is compensated by a mutation in the other. The study presented in section 2.2 has been carried out to prove that an explicit introduction of solvent into the correlated mutations concept indeed yields qualitative improvement of existing approaches. For this, we have used the data on interfacial solvent obtained from the SCOWLP database (the whole PDB) to construct a “wet” similarity matrix. This matrix has been used for prediction of protein contacts together with a well-established “dry” matrix. We have analyzed two datasets containing 50 domains and 10 domain pairs, and have compared the results obtained by using several combinations of both “dry” and “wet” matrices. We have found that for predictions for both intra- and interdomain contacts the introduction of a combination of a “dry” and a “wet” similarity matrix improves the predictions in comparison to the “dry” one alone. Our analysis opens up the idea that the consideration of water may have an impact on the improvement of the contact predictions obtained by correlated mutations approaches. There are two principally novel aspects in this study in the context of the used correlated mutations methodology : i) the first introduction of solvent explicitly into the correlated mutations approach; ii) the use of the definition of protein-protein interfaces, which is essentially different from many other works in the field because of taking into account physico-chemical properties of amino acids and not being exclusively based on distance cut-offs. II. The second part of the thesis is focused on properties of fluorinated amino acids in protein environments. In general, non-canonical amino acids with newly designed side-chain functionalities are powerful tools that can be used to improve structural, catalytic, kinetic and thermodynamic properties of peptides and proteins, which otherwise are not feasible within the use of canonical amino acids. In this context fluorinated amino acids have increasingly gained in importance in protein chemistry because of fluorine's unique properties: high electronegativity and a small atomic size. Despite the wide use of fluorine in drug design, properties of fluorine in protein environments have not been yet extensively studied. The aims of this part of the dissertation were: 1. to analyze the basic properties of fluorinated amino acids such as electrostatic and geometric characteristics, hydrogen bonding abilities, hydration properties and conformational preferences (section 3.1) 2. to describe the behavior of fluorinated amino acids in systems emulating protein environments (section 3.2, section 3.3) First, to characterize fluorinated amino acids side chains we have used fluorinated ethane derivatives as their simplified models and applied a quantum mechanics approach. Properties such as charge distribution, dipole moments, volumes and size of the fluoromethylated groups within the model have been characterized. Hydrogen bonding properties of these groups have been compared with the groups typically presented in natural protein environments. We have shown that hydrogen and fluorine atoms within these fluoromethylated groups are weak hydrogen bond donors and acceptors. Nevertheless they should not be disregarded for applications in protein engineering. Then, we have implemented four fluorinated L-amino acids for the AMBER force field and characterized their conformational and hydration properties at the MD level. We have found that hydrophobicity of fluorinated side chains grows with the number of fluorine atoms and could be explained in terms of high electronegativity of fluorine atoms and spacial demand of fluorinated side-chains. These data on hydration agrees with the results obtained in the experimental work performed by our collaborators. We have rationally engineered systems that allow us to study fluorine properties and extract results that could be extrapolated to proteins. For this, we have emulated protein environments by introducing fluorinated amino acids into a parallel coiled-coil and enzyme-ligand chymotrypsin systems. The results on fluorination effect on coiled-coil dimerization and substrate affinities in the chymotrypsin active site obtained by MD, molecular docking and free energy calculations are in strong agreement with experimental data obtained by our collaborators. In particular, we have shown that fluorine content and position of fluorination can considerably change the polarity and steric properties of an amino acid side chain and, thus, can influence the properties that a fluorinated amino acid reveals within a native protein environment. III. Coiled-coils typically consist of two to five right-handed α-helices that wrap around each other to form a left-handed superhelix. The interface of two α-helices is usually represented by hydrophobic residues. However, the analysis of protein databases revealed that in natural occurring proteins up to 20% of these positions are populated by polar and charged residues. The impact of these residues on stability of coiled-coil system is not clear. MD simulations together with free energy calculations have been utilized to estimate favourable interaction partners for uncommon amino acids within the hydrophobic core of coiled-coils (Chapter 4). Based on these data, the best hits among binding partners for one strand of a coiled-coil bearing a charged amino acid in a central hydrophobic core position have been selected. Computational data have been in agreement with the results obtained by our collaborators, who applied phage display technology and CD spectroscopy. This combination of theoretical and experimental approaches allowed to get a deeper insight into the stability of the coiled-coil system. To conclude, this thesis widens existing concepts of protein structural biology in three areas of its current importance. We expand on the role of solvent in protein interfaces, which contributes to the knowledge of physico-chemical properties underlying protein-protein interactions. We develop a deeper insight into the understanding of the fluorine's impact upon its introduction into protein environments, which may assist in exploiting the full potential of fluorine's unique properties for applications in the field of protein engineering and drug design. Finally we investigate the mechanisms underlying coiled-coil system folding. The results presented in the thesis are of definite importance for possible applications (e.g. introduction of solvent explicitly into the scoring function) into protein folding, docking and rational design methods. The dissertation consists of four chapters: ● Chapter 1 contains an introduction to the topic of protein-protein interactions including basic concepts and an overview of the present state of research in the field. ● Chapter 2 focuses on the studies of the role of solvent in protein interfaces. ● Chapter 3 is devoted to the work on fluorinated amino acids in protein environments. ● Chapter 4 describes the study of coiled-coils folding properties. The experimental parts presented in Chapters 3 and 4 of this thesis have been performed by our collaborators at FU Berlin. Sections 2.1, 2.2, 3.1, 3.2 and Chapter 4 have been submitted/published in peer-reviewed international journals. Their organization follows a standard research article structure: Abstract, Introduction, Methodology, Results and discussion, and Conclusions. Section 3.3, though not published yet, is also organized in the same way. The literature references are summed up together at the end of the thesis to avoid redundancy within different chapters.

Proteins have an indispensable role in the cell. They carry out a wide variety of structural, catalytic and signaling functions in all known biological systems. To perform their biological functions, proteins establish interactions with other bioorganic molecules including other proteins. Therefore, protein-protein interactions is one of the central topics in molecular biology. My thesis is devoted to three different topics in the field of protein-protein interactions. The first one focuses on solvent contribution to protein interfaces as it is an important component of protein complexes. The second topic discloses the structural and functional potential of fluorine's unique properties, which are attractive for protein design and engineering not feasible within the scope of canonical amino acids. The last part of this thesis is a study of the impact of charged amino acid residues within the hydrophobic interface of a coiled-coil system, which is one of the well-established model systems for protein-protein interactions studies. I. The majority of proteins interact in vivo in solution, thus studies of solvent impact on protein-protein interactions could be crucial for understanding many processes in the cell. However, though solvent is known to be very important for protein-protein interactions in terms of structure, dynamics and energetics, its effects are often disregarded in computational studies because a detailed solvent description requires complex and computationally demanding approaches. As a consequence, many protein residues, which establish water-mediated interactions, are neither considered in an interface definition. In the previous work carried out in our group the protein interfaces database (SCOWLP) has been developed. This database takes into account interfacial solvent and based on this classifies all interfacial protein residues of the PDB into three classes based on their interacting properties: dry (direct interaction), dual (direct and water-mediated interactions), and wet spots (residues interacting only through one water molecule). To define an interaction SCOWLP considers a donor–acceptor distance for hydrogen bonds of 3.2 Å, for salt bridges of 4 Å, and for van der Waals contacts the sum of the van der Waals radii of the interacting atoms. In previous studies of the group, statistical analysis of a non-redundant protein structure dataset showed that 40.1% of the interfacial residues participate in water-mediated interactions, and that 14.5% of the total residues in interfaces are wet spots. Moreover, wet spots have been shown to display similar characteristics to residues contacting water molecules in cores or cavities of proteins. The goals of this part of the thesis were: 1. to characterize the impact of solvent in protein-protein interactions 2. to elucidate possible effects of solvent inclusion into the correlated mutations approach for protein contacts prediction To study solvent impact on protein interfaces a molecular dynamics (MD) approach has been used. This part of the work is elaborated in section 2.1 of this thesis. We have characterized properties of water-mediated protein interactions at residue and solvent level. For this purpose, an MD analysis of 17 representative complexes from SH3 and immunoglobulin protein families has been performed. We have shown that the interfacial residues interacting through a single water molecule (wet spots) are energetically and dynamically very similar to other interfacial residues. At the same time, water molecules mediating protein interactions have been found to be significantly less mobile than surface solvent in terms of residence time. Calculated free energies indicate that these water molecules should significantly affect formation and stability of a protein-protein complex. The results obtained in this part of the work also suggest that water molecules in protein interfaces contribute to the conservation of protein interactions by allowing more sequence variability in the interacting partners, which has important implications for the use of the correlated mutations concept in protein interactions studies. This concept is based on the assumption that interacting protein residues co-evolve, so that a mutation in one of the interacting counterparts is compensated by a mutation in the other. The study presented in section 2.2 has been carried out to prove that an explicit introduction of solvent into the correlated mutations concept indeed yields qualitative improvement of existing approaches. For this, we have used the data on interfacial solvent obtained from the SCOWLP database (the whole PDB) to construct a “wet” similarity matrix. This matrix has been used for prediction of protein contacts together with a well-established “dry” matrix. We have analyzed two datasets containing 50 domains and 10 domain pairs, and have compared the results obtained by using several combinations of both “dry” and “wet” matrices. We have found that for predictions for both intra- and interdomain contacts the introduction of a combination of a “dry” and a “wet” similarity matrix improves the predictions in comparison to the “dry” one alone. Our analysis opens up the idea that the consideration of water may have an impact on the improvement of the contact predictions obtained by correlated mutations approaches. There are two principally novel aspects in this study in the context of the used correlated mutations methodology : i) the first introduction of solvent explicitly into the correlated mutations approach; ii) the use of the definition of protein-protein interfaces, which is essentially different from many other works in the field because of taking into account physico-chemical properties of amino acids and not being exclusively based on distance cut-offs. II. The second part of the thesis is focused on properties of fluorinated amino acids in protein environments. In general, non-canonical amino acids with newly designed side-chain functionalities are powerful tools that can be used to improve structural, catalytic, kinetic and thermodynamic properties of peptides and proteins, which otherwise are not feasible within the use of canonical amino acids. In this context fluorinated amino acids have increasingly gained in importance in protein chemistry because of fluorine's unique properties: high electronegativity and a small atomic size. Despite the wide use of fluorine in drug design, properties of fluorine in protein environments have not been yet extensively studied. The aims of this part of the dissertation were: 1. to analyze the basic properties of fluorinated amino acids such as electrostatic and geometric characteristics, hydrogen bonding abilities, hydration properties and conformational preferences (section 3.1) 2. to describe the behavior of fluorinated amino acids in systems emulating protein environments (section 3.2, section 3.3) First, to characterize fluorinated amino acids side chains we have used fluorinated ethane derivatives as their simplified models and applied a quantum mechanics approach. Properties such as charge distribution, dipole moments, volumes and size of the fluoromethylated groups within the model have been characterized. Hydrogen bonding properties of these groups have been compared with the groups typically presented in natural protein environments. We have shown that hydrogen and fluorine atoms within these fluoromethylated groups are weak hydrogen bond donors and acceptors. Nevertheless they should not be disregarded for applications in protein engineering. Then, we have implemented four fluorinated L-amino acids for the AMBER force field and characterized their conformational and hydration properties at the MD level. We have found that hydrophobicity of fluorinated side chains grows with the number of fluorine atoms and could be explained in terms of high electronegativity of fluorine atoms and spacial demand of fluorinated side-chains. These data on hydration agrees with the results obtained in the experimental work performed by our collaborators. We have rationally engineered systems that allow us to study fluorine properties and extract results that could be extrapolated to proteins. For this, we have emulated protein environments by introducing fluorinated amino acids into a parallel coiled-coil and enzyme-ligand chymotrypsin systems. The results on fluorination effect on coiled-coil dimerization and substrate affinities in the chymotrypsin active site obtained by MD, molecular docking and free energy calculations are in strong agreement with experimental data obtained by our collaborators. In particular, we have shown that fluorine content and position of fluorination can considerably change the polarity and steric properties of an amino acid side chain and, thus, can influence the properties that a fluorinated amino acid reveals within a native protein environment. III. Coiled-coils typically consist of two to five right-handed α-helices that wrap around each other to form a left-handed superhelix. The interface of two α-helices is usually represented by hydrophobic residues. However, the analysis of protein databases revealed that in natural occurring proteins up to 20% of these positions are populated by polar and charged residues. The impact of these residues on stability of coiled-coil system is not clear. MD simulations together with free energy calculations have been utilized to estimate favourable interaction partners for uncommon amino acids within the hydrophobic core of coiled-coils (Chapter 4). Based on these data, the best hits among binding partners for one strand of a coiled-coil bearing a charged amino acid in a central hydrophobic core position have been selected. Computational data have been in agreement with the results obtained by our collaborators, who applied phage display technology and CD spectroscopy. This combination of theoretical and experimental approaches allowed to get a deeper insight into the stability of the coiled-coil system. To conclude, this thesis widens existing concepts of protein structural biology in three areas of its current importance. We expand on the role of solvent in protein interfaces, which contributes to the knowledge of physico-chemical properties underlying protein-protein interactions. We develop a deeper insight into the understanding of the fluorine's impact upon its introduction into protein environments, which may assist in exploiting the full potential of fluorine's unique properties for applications in the field of protein engineering and drug design. Finally we investigate the mechanisms underlying coiled-coil system folding. The results presented in the thesis are of definite importance for possible applications (e.g. introduction of solvent explicitly into the scoring function) into protein folding, docking and rational design methods. The dissertation consists of four chapters: ● Chapter 1 contains an introduction to the topic of protein-protein interactions including basic concepts and an overview of the present state of research in the field. ● Chapter 2 focuses on the studies of the role of solvent in protein interfaces. ● Chapter 3 is devoted to the work on fluorinated amino acids in protein environments. ● Chapter 4 describes the study of coiled-coils folding properties. The experimental parts presented in Chapters 3 and 4 of this thesis have been performed by our collaborators at FU Berlin. Sections 2.1, 2.2, 3.1, 3.2 and Chapter 4 have been submitted/published in peer-reviewed international journals. Their organization follows a standard research article structure: Abstract, Introduction, Methodology, Results and discussion, and Conclusions. Section 3.3, though not published yet, is also organized in the same way. The literature references are summed up together at the end of the thesis to avoid redundancy within different chapters.

Telemedical methods enable remote patient monitoring and healthcare at a distance. Besides, fitness tracker and sport watches are currently trending electronic products to generate awareness of health parameters in daily life. Especially, the long-term and continuous measurement of electrophysiological signals such as electrocardiogramm (ECG) becomes increasingly attractive for telemedical applications. Typically used disposable Ag/AgCl wet electrodes for good skin-electrode contact can potentially cause skin irritation and rashes. This paper presents a low cost, individual and flexible substrate for skin electrodes to be applied in future consumer electronic or professional applications. It enables an alternative contact method of the electrode to the skin by applying a pressure during the measurement and hence good contact. If no measurement is needed pressure can be released and the electrode loses skin contact. The 3D printed polymer module is 4 mm thick and comprises a pressure chamber, silver electrodes and insulation layer. The airtight printed membrane of flexible filament, which expands when inflating the chamber, may be printed in different thicknesses and shapes, much thinner than the present 4mm. This enables a high individuality for various applications. Pressure up to 150 kPa was applied and leads to dilatation of 1400 μm. First tests on skin when measuring electrodermal activity (EDA) show promising results for future applications.