A5072960998- Cellular Mechanics and Interactions
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- 3D Printing in Biomedical Research
- Lipid Membrane Structure and Behavior
- Cardiomyopathy and Myosin Studies
- Microfluidic and Bio-sensing Technologies
- Force Microscopy Techniques and Applications
- Autophagy in Disease and Therapy
- RNA and protein synthesis mechanisms
- Cardiac electrophysiology and arrhythmias
- Neuroinflammation and Neurodegeneration Mechanisms
- Diatoms and Algae Research
- Virus-based gene therapy research
- Neurogenesis and neuroplasticity mechanisms
- Biotin and Related Studies
- Cell Adhesion Molecules Research
- Sphingolipid Metabolism and Signaling
- Angiogenesis and VEGF in Cancer
- Tissue Engineering and Regenerative Medicine
- Connexins and lens biology
- Hippo pathway signaling and YAP/TAZ
- Axon Guidance and Neuronal Signaling
- Skin and Cellular Biology Research
- Geology and Paleoclimatology Research
Forschungszentrum Jülich
2015-2025
Biomechanics Institute of Valencia
2011
Institute for Complex Systems
2011
Significance For decades, researchers have been trying to unravel one of the key questions in cell biology regarding keratin intermediate filament function protecting epithelial cells against mechanical stress. many different reasons, however, this fundamental hypothesis was still unproven. Here we answer pivotal question by use KO lacking complete gene clusters result total loss filaments. This lack significantly softens cells, reduces viscosity, and elevates plastic deformation on force...
AbstractAutophagy, a pathway primarily relevant for cell survival, and apoptosis, process invariably leading to death, are the two main mechanisms of cellular self-destruction, which essential in growth, neurodegeneration, tumor suppression, stress immune response. Currently, potential crosstalk between apoptosis autophagy is subject intensive investigations since recently some direct junctions became obvious. The respective protein-protein interaction network, however, remains be elucidated...
Direct delivery of proteins and peptides into living mammalian cells has been accomplished using phospholipid liposomes as carrier particles. Such are usually taken up via endocytosis where the main part their cargo is degraded in lysosomes before reaching its destination. Here, fusogenic liposomes, a newly developed molecular system, were used for protein delivery. When such loaded with water-soluble brought contact cells, liposomal membrane efficiently fused cellular plasma delivering...
Cardiomyocytes are responsible for the permanent blood flow by coordinated heart contractions. This vital function is accomplished over a long period of time with almost same performance, although properties, as its elasticity, change drastically upon aging or result diseases like myocardial infarction. In this paper we have analyzed late rat embryonic muscle cells' morphology, sarcomere/costamere formation and force generation patterns on substrates various elasticities ranging from ∼1 to...
Abstract Adherent cells exert traction forces on to their environment which allows them migrate, maintain tissue integrity, and form complex multicellular structures during developmental morphogenesis. Traction force microscopy (TFM) enables the measurement of an elastic substrate thereby provides quantitative information cellular mechanics in a perturbation-free fashion. In TFM, is usually calculated via solution linear system, complicated by undersampled input data, acquisition noise,...
Efficient delivery of biomolecules into membranes living cells as well cell surface modifications are major biotechnological challenges. Here, novel liposome systems based on neutral and cationic lipids in combination with modified by aromatic groups introduced for such applications. The fusion efficiency these was tested single culture like HEK293, myofibroblasts, cortical neurons, human macrophages, smooth muscle cells, even tissue. Fusogenic liposomes enabled highly efficient...
In this paper a rapid and highly efficient method for controlled incorporation of fluorescent lipids into living mammalian cells is introduced. Here, the molecules have two consecutive functions: First, they trigger membrane fusion between cellular plasma membranes lipid bilayers their carrier particles, so called fusogenic liposomes, second, after insertion these enable fluorescence imaging cell traffic processes. We tested derivatives following essential fusion: Ceramide, sphingomyelin,...
Abstract Targeting of diseased cells is one the most urgently needed prerequisites for a next generation potent pharmaceuticals. Different approaches pursued fail mainly due to lack specific surface markers. Developing an RNA-based methodology, we can now ensure precise cell targeting combined with selective expression effector proteins therapy, diagnostics or steering. The combination molecular properties antisense technology and mRNA therapy functional RNA secondary structures allowed us...
Iron limitation often results in increased cellular silica contents of diatoms, suggesting that diatoms grow thicker and possibly mechanically stronger frustules when limited. We performed stability measurements for six diatom species grown under iron‐limitation iron‐sufficient conditions. Frustule strength all iron limitation, with this effect being statistically significant four them. Valve morphology content the pennate Fragilariopsis kerguelensis centric Coscinodiscus wailesii changed...
Highly efficient, biocompatible, and fast nucleic acid delivery methods are essential for biomedical applications research. At present, two main strategies used to this end. In non-viral transfection liposome- or polymer-based formulations transfer cargo into cells via endocytosis, whereas viral carriers enable direct the cell cytoplasm. Here, we introduce a new generation of liposomes delivery, which immediately fuse with cellular plasma membrane upon contact functional directly For maximum...
Living animal cells are strongly influenced by the mechanical properties of their environment. To model physiological conditions ultrasoft cell culture substrates, in some instances with elasticity (Young's modulus) only 1 kPa, mandatory. Due to long shelf life PDMS-based elastomers a popular choice. However, uncertainty about additives commercial formulations and difficulties reach very soft materials limit use. Here, we produced silicone from few, chemically defined commercially available...
Microglia-the brain's primary immune cells-exert a tightly regulated cascade of pro- and anti-inflammatory effects upon brain pathology, either promoting regeneration or neurodegeneration. Therefore, harnessing microglia emerges as potential therapeutic concept in neurological research. Recent studies suggest that-besides being affected by chemokines cytokines-various cell entities the relevantly respond to mechanical properties their microenvironment. For example, we lately reported...
Transferring nucleic acids into mammalian cells heavily influences life science for decades. While first applications mainly dealt with DNA transfer various purposes as e.g., plasmid encoded protein expression or generation of mutant strains, subsequent additionally transferred RNA molecules small lengths specific knockdown (RNAi) site-specific genome modification (gRNA). Significant improvements in full length mRNA and extension lifetimes allows their use transient latest times. For all...
Animal cells use traction forces to sense the mechanics and geometry of their environment. Measuring these requires a workflow combining cell experiments, image processing force reconstruction based on elasticity theory. Such procedures have been established before mainly for planar substrates, in which case one can Green's function formalism. Here we introduce worksflow measure cardiac myofibroblasts non-planar elastic substrates. Soft substrates with wave-like topology were micromolded...
Efficient and reliable transfer of nucleic acids for therapy applications is a major challenge. Stabilization lipo- polyplexes has already been successfully achieved by PEGylation. This modification reduces the interaction with serum proteins thus prevents lipoplexes from being cleared reticuloendothelial system. Problematically, this stabilization simultaneously leads to reduced efficiencies compared non-PEGylated complexes. However, reduction in efficiency can be used advantage since...
Surface patterning with complex molecules has become a valuable tool in cell biology and biotechnology, as it enables one to control shape function culture. However, this technique for micro-contact printing is normally performed on rigid substrates, e.g. Petri dishes or glass. Despite the fact that these substrates can easily be patterned they are artificially stiff environments cells affecting their morphology function. Those artifacts avoided tissue elasticity resembling leading nature...
In the brain, neural stem cells (NSC) are tightly regulated by external signals and biophysical cues mediated local microenvironment or "niche." particular, influence of tissue elasticity, known to fundamentally affect function various cell types in body, on NSC remains poorly understood. We, accordingly, aimed characterize effects elastic substrates critical functions. Primary rat were grown as monolayers polydimethylsiloxane- (PDMS-) based gels. PDMS-coated culture plates, simulating...
Abstract The Eph‐ephrin system plays pivotal roles in cell adhesion and migration. receptor‐like functions of the ephrin ligands allow regulation intracellular processes via reverse signaling. γ‐Secretase mediated processing ephrin‐B has previously been linked to activation Src, a kinase crucial for focal podosome phosphorylation. Here, we analyzed role γ‐secretase stimulation ephrin‐B2 signaling migration mouse embryonic stem derived microglia. proteolytic generation domain (ICD) by...
Purification of defined cell populations from mixed primary sources is essential for many biomedical and biotechnological applications but often very difficult to accomplish due missing specific surface markers. In this study, we developed a new approach efficient population separation based on the membrane fusion characteristics distinct types upon treatment with fusogenic liposomes. When such liposomes are conjugated biotin, can be efficiently functionalized by biotin after liposomal while...
The efficient and biocompatible transfer of nucleic acids into mammalian cells for research applications or medical purposes is a long-standing, challenging task. Viral transduction the most system, but often entails high safety levels potential health impairments patients in applications. Lipo- polyplexes are commonly used systems result comparably low efficiencies. Moreover, inflammatory responses caused by cytotoxic side effects were reported these methods. Often accountable various...
Cell migration requires the initial formation of cell protrusions, lamellipodia and/or filopodia, attachment leading lamella to extracellular cues and efficient recycling focal contacts at edge. The small calcium binding EF-hand protein S100A4 has been shown promote motility but direct molecular mechanisms responsible remain be elucidated. In this work, we provide new evidences indicating that elevated levels affect stability filopodia prevent maturation complexes. Increasing in a rat...