INMdok (Leibniz Institute for New Materials)
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Label-Free Imaging of Cholesterol Assemblies Reveals Hidden Nanomechanics of Breast Cancer Cells
Get PDFAbstract Tumor cells present profound alterations in their composition, structural organization, and functional properties. A landmark of cancer cells is an overall altered mechanical phenotype, which so far are linked to changes in their cytoskeletal regulation and organization. Evidence exists that the plasma membrane (PM) of cancer cells also shows drastic changes in its composition and organization. However, biomechanical characterization of PM remains limited mainly due to the difficulties encountered to investigate it in a quantitative and label-free manner. Here, the biomechanical properties of PM of a series of MCF10 cell lines, used as a model of breast cancer progression, are investigated. Notably, a strong correlation between the cell PM elasticity and oncogenesis is observed. The altered membrane composition under cancer progression, as emphasized by the PM-associated cholesterol levels, leads to a stiffening of the PM that is uncoupled from the elastic cytoskeletal properties. Conversely, cholesterol depletion of metastatic cells leads to a softening of their PM, restoring biomechanical properties similar to benign cells. As novel therapies based on targeting membrane lipids in cancer cells represent a promising approach in the field of anticancer drug development, this method contributes to deciphering the functional link between PM lipid content and disease
Printed Degradable Optical Waveguides for Guiding Light into Tissue
Get PDFAbstract Optogenetics and photonic technologies are changing the future of medicine. To implement light-based therapies in the clinic, patient-friendly devices that can deliver light inside the body while offering tunable properties and compatibility with soft tissues are needed. Here extrusion printing of degradable, hydrogel-based optical waveguides with optical losses as low as 0.1 dB cm−1 at visible wavelengths is described. Core-only and core-cladding fibers are printed at room temperature from polyethylene glycol (PEG)-based and PEG/Pluronic precursors, and cured by in situ photopolymerization. The obtained waveguides are flexible, with mechanical properties tunable within a tissue-compatible range. Degradation times are also tunable by adjusting the molar mass of the diacrylate gel precursors, which are synthesized by linking PEG diacrylate (PEGDA) with varying proportions of DL-dithiothreitol (DTT). The printed waveguides are used to activate photochemical and optogenetic processes in close-to-physiological environments. Light-triggered migration of cells in a photoresponsive 3D hydrogel and drug release from an optogenetically-engineered living material by delivering light across >5 cm of muscle tissue are demonstrated. These results quantify the in vitro performance, and reflect the potential of the printed degradable fibers for in vivo and clinical applications
Macroscopic self-evolution of dynamic hydrogels to create hollow interiors
Get PDFA solid-to-hollow evolution in macroscopic structure is challenging in synthetic materials. Herein we report a fundamentally new strategy for guiding macroscopic, unidirectional shape-evolution of materials without compromising the material’s integrity, based on the creation of a field with a “swelling pole” and a “shrinking pole” to drive polymers to disassemble, migrate, and resettle in the targeted region. We demonstrate this concept by using dynamic hydrogels containing anchored acrylic ligands and hydrophobic long alkyl chains. Adding water molecules and ferric ions (Fe3+) to induce a swelling-shrinking field transforms the hydrogels from solid to hollow. The strategy is versatile in the generation of various closed hollow objects including spheres, helix tubes, and cubes with different diameters, for different applications
Light-regulated growth from dynamic swollen substrates for making rough surfaces
Get PDFNatural organic structures form via a growth mode in which nutrients are absorbed, transported, and integrated. In contrast, synthetic architectures are constructed through fundamentally different methods, such as assembling, molding, cutting, and printing. Here, we report a photoinduced strategy for regulating the localized growth of microstructures from the surface of a swollen dynamic substrate, by coupling photolysis, photopolymerization, and transesterification together. Photolysis is used to generate dissociable ionic groups to enhance the swelling ability that drives nutrient solutions containing polymerizable components into the irradiated region, photopolymerization converts polymerizable components into polymers, and transesterification incorporates newly formed polymers into the original network structure. Such light-regulated growth is spatially controllable and dose-dependent and allows fine modulation of the size, composition, and mechanical properties of the grown structures. We also demonstrate the application of this process in the preparation of microstructures on a surface and the restoration of large-scale surface damage
Migration of Cytotoxic T Lymphocytes in 3D Collagen Matrices
No full textCD8+ cytotoxic T lymphocytes (CTL) and natural killer cells are the main cytotoxic killer cells of the human body to eliminate pathogen-infected or tumorigenic cells (also known as target cells). To find their targets, they have to navigate and migrate through complex biological microenvironments, a key component of which is the extracellular matrix (ECM). The mechanisms underlying killer cell?s navigation are not well understood. To mimic an ECM, we use a matrix formed by different collagen concentrations and analyze migration trajectories of primary human CTLs. Different migration patterns are observed and can be grouped into three motility types: slow, fast, and mixed. The dynamics are well described by a two-state persistent random walk model, which allows cells to switch between slow motion with low persistence and fast motion with high persistence. We hypothesize that the slow motility mode describes CTLs creating channels through the collagen matrix by deforming and tearing apart collagen fibers and that the fast motility mode describes CTLs moving within these channels. Experimental evidence supporting this scenario is presented by visualizing migrating T cells following each other on exactly the same track and showing cells moving quickly in channel-like cavities within the surrounding collagen matrix. Consequently, the efficiency of the stochastic search process of CTLs in the ECM should strongly be influenced by a dynamically changing channel network produced by the killer cells themselves
Printed soft optical waveguides for delivering light into deep tissue
Get PDFTo implement light-based diagnosis and therapies in the clinic, implantable patient-friendly devices that can deliver light inside the body while being compatible with soft tissues are needed. This Thesis presents the development of optical waveguides for guiding light into tissue, obtained by printing technologies from three different polymer combinations. Firstly, D,L-dithiothreitol (DTT) bridged PEG diacrylate were synthesized and printed into waveguides, which exhibited tunable mechanical properties and degradability, and low optical losses (as low as 0.1 dB cm-1 in visible range). Secondly, degradable waveguides from amorphous poly(D,L-lactide) and derived copolymers were developed by printing, which showed elasticity at body temperature and could guide VIS to NIR light in tissue for tens of centimeters. At last, soft and stretchable optical waveguides consisting of polydimethylsiloxane (PDMS) core and acrylated Pluronic F127 cladding were fabricated by coaxial extrusion printing, which could be stretched to 4 times of their length and showed optical loss values in tissue as low as 0.13 -0.34 dB cm-1 in the range of 405-520 nm. For proof-of-concept, above printed optical waveguides were used to deliver light across 5-8 cm tissue to remotely activate photochemical processes in in vitro cell cultures. The presented work exemplifies how rational study of medically approved biomaterials can lead to useful and cost-effective optical components for light applications.Neue optische Technologien verändern die Zukunft der Medizin und fördern die Entwicklung von Implantaten, die im Körper Licht abgeben. Diese Arbeit beschreibt drei gewebekompatible, optische Wellen¬leiter für medizinische Zwecke, die mit 3D-Extrusionsdruck gefertigt werden. Zum einem wurden Wellen¬leiter mit einstellbaren mechanischen Eigenschaften und kontrollierter Abbaubarkeit im Körper als Funktion des Dithio¬threitol (DTT)-Anteils in DTT-modifizierten Poly¬ethylen¬glykol¬diacrylat-Hydro¬gelen entwickelt. Die bei der Extrusion in-situ-photopolymerisierten Wellen¬leiter haben nur 0,1 dB/cm optischen Verlust im VIS-Bereich und wurden verwendet, um photo¬chemische Prozesse in In-vitro-Zellkulturen zu aktivieren. Zum anderen wurden im Körper abbaubare Wellenleiter aus amorphem Poly(D,L-Lactid) und dessen Copolymeren gedruckt. Diese Wellenleiter sind bei Körpertemperatur elastisch und leiten in mehreren zehn Zentimetern Gewebe Licht vom VIS- bis NIR-Bereich. Schließlich wurden mit koaxialem Extrusions¬druck weiche und dehnbare Wellenleiter hergestellt, die aus einem PDMS-Kern und einer acrylierten Pluronic F127 Hülle bestehen. Diese Wellenleiter sind aufs Vierfache dehnbar und haben in Gewebe nur 0,13 bis 0,34 dB/cm optische Verluste bei 405-520 nm. Die vorgestellte Arbeit zeigt, wie Materialauswahl mit Drucktechnologien kombiniert werden können, um optische Wellenleiter für medizinische Anwendungen mit bemerkenswerter Leistung bei angemessenem Aufwand zu entwickeln
Widerstandsfähige Leiterbahnen durch Inkjet-gedruckte sinterfreie, leitfähige Hybridtinten auf Faltschachtelkarton am Beispiel faltbarer 3D-UHF Antennen : PTS-Abschlussbericht zum Forschungsvorhaben PTS-IGF BG 19957 „IGLU“
Get PDFZiel des Forschungsvorhabens war, mit neuartigen flexiblen Hybridtinten Leiterbahnen für integrierte Elektronik auf faserbasierte Substrate zu drucken. Die Kombination aus neuen Materialien und verbesserten Prozessen wird folgende Vorteile bringen:
- Flexibilität: gedruckte Strukturen halten branchentypischen Verarbei-tungsverfahren stand
- Sinterfreiheit: die Strukturen sind direkt nach dem Drucken leitfähig
- Einfachheit: die Tinten können mit Standard-Inkjet-Druckern verdruckt werden[...
Synthesis and Biopharmaceutical Characterization of Amphiphilic Squalenyl Derivative Based Versatile Drug Delivery Platform
Get PDFLimited drug loading capacity (LC), mostly below 5% w/w, is a significant drawback of nanoparticulate drug delivery systems (DDS). Squalenoylation technology, which employs bioconjugation of squalenyl moiety and drug, allows self-assemble of nanoparticles (NPs) in aqueous media with significantly high LC (>30% w/w). The synthesis and particle preparation of squalenoylated prodrugs are, however, not facile for molecules with multiple reactive groups. Taking a different approach, we describe the synthesis of amphiphilic squalenyl derivatives (SqDs) as well as the physicochemical and biopharmaceutical characterizations of their self-assembled NPs as DDSs. The SqDs included in this study are (i) cationic squalenyl diethanolamine (ii) PEGylated SqD (PEG 750 Da), (iii) PEGylated SqD (PEG 3,000 Da), and (iv) anionic squalenyl hydrogen sulfate. All four SqDs self-assemble into NPs in a size range from 100 to 200 nm in an aqueous solution. Furthermore, all NP derivatives demonstrate appropriate biocompatibility and adequate colloidal stability in physiological relevant pH environments. The mucoprotein binding of PEGylated NPs is reduced compared to the charged NPs. Most importantly, this technology allows excellent LC (at maximum of 45% w/w) of a wide range of multifunctional compounds, varying in physicochemical properties and molecular weight. Interestingly, the drug release profile can be tuned by different loading methods. In summary, the SqD-based NPs appear as versatile drug delivery platforms
Probiomimetics—Novel Lactobacillus-Mimicking Microparticles Show Anti-Inflammatory and Barrier-Protecting Effects in Gastrointestinal Models
Get PDFAbstract There is a lack of efficient therapies to treat increasingly prevalent autoimmune diseases, such as inflammatory bowel disease and celiac disease. Membrane vesicles (MVs) isolated from probiotic bacteria have shown tremendous potential for treating intestinal inflammatory diseases. However, possible dilution effects and rapid elimination in the gastrointestinal tract may impair their application. A cell-free and anti-inflammatory therapeutic system?probiomimetics?based on MVs of probiotic bacteria (Lactobacillus casei and Lactobacillus plantarum) coupled to the surface of microparticles is developed. The MVs are isolated and characterized for size and protein content. MV morphology is determined using cryoelectron microscopy and is reported for the first time in this study. MVs are nontoxic against macrophage-like dTHP-1 and enterocyte-like Caco-2 cell lines. Subsequently, the MVs are coupled onto the surface of microparticles according to facile aldehyde-group functionalization to obtain probiomimetics. A significant reduction in proinflammatory TNF-α level (by 86%) is observed with probiomimetics but not with native MVs. Moreover, it is demonstrated that probiomimetics have the ability to ameliorate inflammation-induced loss of intestinal barrier function, indicating their potential for further development into an anti-inflammatory formulation. These engineered simple probiomimetics that elicit striking anti-inflammatory effects are a key step toward therapeutic MV translation
Persistent and reversible solid iodine electrodeposition in nanoporous carbons
Get PDFAqueous iodine based electrochemical energy storage is considered a potential candidate to improve sustainability and performance of current battery and supercapacitor technology. It harnesses the redox activity of iodide, iodine, and polyiodide species in the confined geometry of nanoporous carbon electrodes. However, current descriptions of the electrochemical reaction mechanism to interconvert these species are elusive. Here we show that electrochemical oxidation of iodide in nanoporous carbons forms persistent solid iodine deposits. Confinement slows down dissolution into triiodide and pentaiodide, responsible for otherwise significant self-discharge via shuttling. The main tools for these insights are in situ Raman spectroscopy and in situ small and wide-angle X-ray scattering (in situ SAXS/WAXS). In situ Raman confirms the reversible formation of triiodide and pentaiodide. In situ SAXS/WAXS indicates remarkable amounts of solid iodine deposited in the carbon nanopores. Combined with stochastic modeling, in situ SAXS allows quantifying the solid iodine volume fraction and visualizing the iodine structure on 3D lattice models at the sub-nanometer scale. Based on the derived mechanism, we demonstrate strategies for improved iodine pore filling capacity and prevention of self-discharge, applicable to hybrid supercapacitors and batteries