Universität Stuttgart
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Item Open Access Precision 3D‐printed cell scaffolds mimicking native tissue composition and mechanics(2020) Erben, Amelie; Hörning, Marcel; Hartmann, Bastian; Becke, Tanja; Eisler, Stephan A.; Southan, Alexander; Cranz, Séverine; Hayden, Oliver; Kneidinger, Nikolaus; Königshoff, Melanie; Lindner, Michael; Tovar, Günter E. M.; Burgstaller, Gerald; Clausen‐Schaumann, Hauke; Sudhop, Stefanie; Heymann, MichaelCellular dynamics are modeled by the 3D architecture and mechanics of the extracellular matrix (ECM) and vice versa. These bidirectional cell‐ECM interactions are the basis for all vital tissues, many of which have been investigated in 2D environments over the last decades. Experimental approaches to mimic in vivo cell niches in 3D with the highest biological conformity and resolution can enable new insights into these cell‐ECM interactions including proliferation, differentiation, migration, and invasion assays. Here, two‐photon stereolithography is adopted to print up to mm‐sized high‐precision 3D cell scaffolds at micrometer resolution with defined mechanical properties from protein‐based resins, such as bovine serum albumin or gelatin methacryloyl. By modifying the manufacturing process including two‐pass printing or post‐print crosslinking, high precision scaffolds with varying Young's moduli ranging from 7‐300 kPa are printed and quantified through atomic force microscopy. The impact of varying scaffold topographies on the dynamics of colonizing cells is observed using mouse myoblast cells and a 3D‐lung microtissue replica colonized with primary human lung fibroblast. This approach will allow for a systematic investigation of single‐cell and tissue dynamics in response to defined mechanical and bio‐molecular cues and is ultimately scalable to full organs.Item Open Access Probleme der Gestaltbildung(1990) Kull, UlrichDie Einzelheiten der Bildung komplexer Gestalten von Lebewesen können nicht vollständig genetisch fixiert sein, da hierzu die Zahl der Gene der Organismen kaum ausreichen würde. Es muß also Vorgänge der Gestaltbildung geben, die auf grund weniger genetischer Festlegungen (Randbedingungen} unter Selbstorganisation ablaufen; sie sind "systemimmanente Eigenschaften". Ein besonderes schönes Beispiel dafür liefern die Radiolarien, die schon Haeckel der ästhetisch ansprechenden Skelettformen wegen sehr schätzte.Item Open Access Insights into the structural and functional properties of the eukaryotic porin Tom40(2012) Gessmann, Dennis; Nußberger, Stephan (Prof. Dr.)Tom40 forms the preprotein conducting channel in the outer membrane of mitochondria enabling transport of up to 1500 different preproteins through an optimized pore environment. Moreover, Tom40 exhibits a voltage-dependent gating mechanism in terms of an ‘electrical switch’ making this eukaryotic beta-barrel a promising target for nanopore based applications. In this work, new bioinformatics methods were developed and verified through practical approaches to shed light on the structural elements of Tom40 facilitating its particular function in mitochondria. Based on these results, Tom40 proteins were designed with modified and optimized structural properties. TmSIP, a physical interaction model developed for TM beta-barrel proteins, was used to identify weakly stable regions in the TM domain of Tom40 from mammals and fungi. Three unfavorable beta-strands were determined for human Tom40A. Via CD and Trp-fluorescence spectroscopy it was shown that substitution of key amino acid residues in theses strands resulted in an improved resistance of the protein to chemical and thermal perturbations. Further, the mutated form of hTom40A was strictly found in its monomeric state. Equal improvements were gained for the apparent stability of Tom40 from Aspergillus fumigatus. Tom40 was isolated and purified in its native state from Neurospora crassa mitochondria. Time-limited proteolysis of native NcTom40 coupled to mass spectrometry revealed comparable protease-accessibility to VDAC isoform 1 from mammals suggesting a similar fold. Thus, a homology model of NcTom40 was developed on the basis of the solved mouse VDAC-1 crystal structure. It was found that Tom40 forms a 19-stranded beta-barrel with an N-terminal alpha-helix inside the pore. Further, a conserved ‘polar slide’ in the pore interior is possibly involved in preprotein translocation and a second conserved domain, termed ‘helix anchor region’, in arresting the helix inside the Tom40 pore. Based on the homology model of NcTom40, the structure and function of the N-terminal domain of Tom40 was addressed. Examination of the model structure revealed two different domains for the N-terminus, the inner-barrel and outer-barrel N-terminus. In vivo investigations showed that both parts prevent a heat-induced dysfunction of Tom40 in N. crassa mitochondria independently. By applying CD spectroscopy the predicted N-terminal alpha-helix could be allocated to the inner-barrel N-terminus. Further, in combination with Trp-fluorescence spectroscopy it was found that the N-terminal alpha-helix unfolds independently from the Tom40 beta-barrel, but is not necessary for pore stability or integrity. However, a conserved amino acid residue, Ile47 of NcTom40, in the inner-barrel N-terminus is essential for the structural integrity of the N-terminal alpha-helix. In conclusion, these results may offer a basis for future works on TM beta-barrel proteins with the aim to alter the structural properties in the absence of a high atomic resolution structure or an established knowledge of the biochemical and biophysical properties.Item Open Access Biophysical investigations of the in vitro effects of shock waves and ultrasound(1993) Brümmer, Franz; Suhr, Dierk; Irmer, Ulrich; Bachleitner, Christoph; Hülser, Dieter F.To investigate the interactions of ultrasonic waves with biological tissues, we developed and standardized several in vitro models. Using these systems - artificial stones, human erythrocytes, L1210 mouse leukemia cells, multicellular spheroids, cavitation assay - we are able to elucidate the mechanisms of interaction as well as the cause of clinically observed side effects.Item Open Access Biological effects of shock waves(1990) Brümmer, Franz; Bräuner, Thomas; Hülser, Dieter F.Extracorporeal shock wave lithotripsy has become established worldwide as the method of choice for the treatment of nephrolithiasis and ureterolithiasis over the last 10 years. Although initial studies showed no damaging effects of the shock waves on organs and tissues, numerous recent reports have presented evidence for severe acute effects and chronic complications after shock wave treatment. The pathophysiological effects on kidneys and the histopathological effects on organs or tissues in man and animal, and also the effects on cells in culture and tumors are sumarized. Suspended and immobilized cell cultures were used to characterize and quantify the efficacy of shock wave. Extended applications of shock waves and possible modifications to shock wave generators are discussed.Item Open Access Funktionen eines regionalen naturwissenschaftlichen Vereins(1994) Kull, UlrichDie Gesellschaft für Naturkunde in Württemberg blickt auf 150 Jahre zurück; sie wurde gegründet im Herbst 1844. Seit ihrer Gründung dient sie der Erforschung der heimischen Natur und der Verknüpfung der Ergebnisse mit den allgemeinen Fortschritten der Naturwissenschaften. Sie arbeitet vor allem im Bereich der Bio- und Geowissenschaften.Item Open Access Cytokinins in different cell compartments after treatment with [8-14C]-kinetin : [abstract](1985) Graf, Josef A.; Dietz, B.; Kull, Ulrich-Item Open Access Prosomes of higher plants share biochemical properties : [abstract](1988) Schliephacke, Martin; Kremp, Anette; Schmid, Hans-Peter; Kull, Ulrich-Item Open Access Anti-adhesive surfaces inspired by bee mandible surfaces(2023) Saccardi, Leonie; Schiebl, Jonas; Balluff, Franz; Christ, Ulrich; Gorb, Stanislav N.; Kovalev, Alexander; Schwarz, OliverPropolis, a naturally sticky substance used by bees to secure their hives and protect the colony from pathogens, presents a fascinating challenge. Despite its adhesive nature, honeybees adeptly handle propolis with their mandibles. Previous research has shown a combination of an anti-adhesive fluid layer and scale-like microstructures on the inner surface of bee mandibles. Our aim was to deepen our understanding of how surface energy and microstructure influence the reduction in adhesion for challenging substances like propolis. To achieve this, we devised surfaces inspired by the intricate microstructure of bee mandibles, employing diverse techniques including roughening steel surfaces, creating lacquer structures using Bénard cells, and moulding resin surfaces with hexagonal patterns. These approaches generated patterns that mimicked the bee mandible structure to varying degrees. Subsequently, we assessed the adhesion of propolis on these bioinspired structured substrates. Our findings revealed that on rough steel and resin surfaces structured with hexagonal dimples, propolis adhesion was significantly reduced by over 40% compared to unstructured control surfaces. However, in the case of the lacquer surface patterned with Bénard cells, we did not observe a significant reduction in adhesion.Item Open Access Introduction - Symposium on Intercellular Communication Stuttgart, 1982(1982) Hülser, Dieter F.Intercellular communication is a postulate of complex multicellular organisation. Signal transfer between cells is possible in different ways: 1.) Long distances of up to 1 m may be bridged by molecules which are produced in distinct cells and are released into the extracellular fluid where they are distributed and interact with receptors on the surface of their target cells (e.g., humoral interaction). 2.) Transmitter substances which have a limited life span or which can be inactivated by inhibitor molecules spread signals only over shorter distances (e.g., synaptic cleft, -200nm). 3.) Information can also be exchanged by direct membrane contact when two molecules interact with each other directly or via linker molecules (e.g., immune system). 4.) Intercellular communication is also possible by channels between adjacent cells, which permit the exchange of ions and molecules and the spread of electric currents; many of those pores are arranged in the membranes of the contacting cells as a quasicristalline structure forming the gap junction. A national symposium on "Intercellular Communication" in Stuttgart on 16 and 17 September 1982 serving the aim of increased "interlaboratory communication" covered most of the above aspects.