A5024854222- Bone Tissue Engineering Materials
- Bone and Dental Protein Studies
- Advanced Electron Microscopy Techniques and Applications
- Calcium Carbonate Crystallization and Inhibition
- Bone health and osteoporosis research
- Electron and X-Ray Spectroscopy Techniques
- Advanced X-ray Imaging Techniques
- Cardiac Valve Diseases and Treatments
- Advanced Fluorescence Microscopy Techniques
- Physiological and biochemical adaptations
- 3D Printing in Biomedical Research
- Fish Ecology and Management Studies
- Bacteriophages and microbial interactions
- Bone Metabolism and Diseases
- Coral and Marine Ecosystems Studies
- Alkaline Phosphatase Research Studies
- Bacterial Genetics and Biotechnology
- Malaria Research and Control
- Paleontology and Stratigraphy of Fossils
- Collagen: Extraction and Characterization
- Photosynthetic Processes and Mechanisms
- Silk-based biomaterials and applications
- Renal and related cancers
- Ion-surface interactions and analysis
- Mosquito-borne diseases and control
Radboud University Nijmegen
2020-2025
Radboud University Medical Center
2020-2025
University Medical Center
2020-2025
University Hospital and Clinics
2024
Radboud Institute for Molecular Life Sciences
2020-2024
Eindhoven University of Technology
2018-2021
Weizmann Institute of Science
2014-2019
Technion – Israel Institute of Technology
2011
Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells associated with increased tubule-interstitial fibrosis in patient autopsy samples. To study effects virus on independent systemic infected human-induced pluripotent stem-cell-derived organoids SARS-CoV-2. Single-cell RNA sequencing indicated injury dedifferentiation activation profibrotic signaling...
Many biomineral crystals form complex non-equilibrium shapes, often via transient amorphous precursors. Also in vitro can be grown with morphologies, such as thin films or nanorods. In many cases this involves charged polymeric additives that a polymer-induced liquid precursor (PILP). Here, we investigate the CaCO3 based PILP process variety of techniques including cryoTEM and NMR. The initial products are 30-50 nm calcium carbonate (ACC) nanoparticles ~2 nanoparticulate texture. We show...
Abstract The mineralized collagen fibril is the basic building block of bone, and commonly pictured as a parallel array ultrathin carbonated hydroxyapatite (HAp) platelets distributed throughout collagen. This orientation often attributed to an epitaxial relationship between HAp molecules inside 2D voids within fibril. Although recent studies have questioned this model, structural matrix HAp, mechanisms by which directs mineralization remain unclear. Here, we use XRD reveal that in are fact...
Abstract Bone formation (osteogenesis) is a complex process in which cellular differentiation and the generation of mineralized organic matrix are synchronized to produce hybrid hierarchical architecture. To study mechanisms osteogenesis health disease, there great need for functional model systems that capture parallel, both processes. Stem cell‐based organoids promising as functional, self‐organizing 3D vitro models studying physiology pathology various tissues. However, human bone, no...
Recently, blood vessels have been implicated in the morphogenesis of various organs. The vasculature is also known to be essential for endochondral bone development, yet underlying mechanism has remained elusive. We show that a unique composition facilitates role endothelium mineralization and morphogenesis. Immunostaining electron microscopy showed developing bones lacks basement membrane, which normally isolates vessel from its surroundings. Further analysis revealed presence collagen type...
Abstract Despite the enormous significance of malaria parasites for global health, some basic features their ultrastructure remain obscure. Here, we apply high-resolution volumetric electron microscopy to examine and compare transmissible male female sexual blood stages Plasmodium falciparum as well more intensively studied asexual revisiting previously described phenomena in 3D. In doing so, challenge widely accepted notion a single mitochondrion by demonstrating presence multiple...
Abstract Fetuin-A is an abundant serum glycoprotein that prevents ectopic calcification. It has a high binding capacity for calcium phosphate and forms calciprotein monomers (CPM) particles (CPP) upon binding. While it also non-collagenous protein in bone, it’s role bone matrix mineralization remains unclear. Using DLS liquid-phase TEM, we identified two-phase assembly process of primary CPPs, which small transient (tCPPs) are formed initially, after larger, stable CPPs form. cell-free...
Bioavailable calcium is maintained by some crustaceans, in particular freshwater crayfish, stabilizing amorphous carbonate (ACC) within reservoir organs--gastroliths, readily providing the Ca(2+) needed to build a new exoskeleton. Despite key scientific and biomedical importance of situ molecular-level picture biogenic ACC its stabilization bioavailable form, description has eluded efforts date. Herein, using multinuclear NMR, we accomplish characterization intact gastroliths crayfish Cherax...
Both in vivo and ex observations support the hypothesis that bone mineral formation proceeds via disordered precursor phases. The characteristics of phases are not well defined, but octacalcium phosphate-like, amorphous calcium HPO42–-enriched were detected. Here we use Raman spectroscopy high-resolution wide-angle X-ray diffraction (WAXD) to characterize map at 2 μm resolution rapidly forming tail fin bones living zebrafish larvae immediately after sacrifice, respectively. shows presence an...
Abstract Aragonite skeletons in corals are key contributors to the storage of atmospheric CO 2 worldwide. Hence, understanding coral biomineralization/calcification processes is crucial for evaluating and predicting effect environmental factors on this process. While biomineralization studies have focused adult corals, exact stage at which initiate mineralization remains enigmatic. Here, we show that minerals first precipitated as amorphous calcium carbonate small aragonite crystallites,...
Abstract Human in vitro bone models can create the possibility for investigation of physiological remodeling while addressing principle replacement, reduction and refinement animal experiments (3R). Current lack cell–matrix interactions their spatiotemporal complexity. To facilitate these analyses, a bone‐mimetic template is developed this study, inspired by bone's extracellular matrix composition organization. Silk fibroin (SF) used as an organic matrix, poly‐aspartic acid (pAsp) to mimic...
Confocal Raman microspectroscopy and fluorescence imaging are two well-established methods providing functional insight into the extracellular matrix living cells tissues, respectively, down to single molecule detection. In however, coexist interact. To acquire information on this cell-matrix interaction, we developed a technique for colocalized, correlative multispectral tissue analysis by implementing high-sensitivity, wide-field confocal microscope. As proof of principle, study early...
Nephrotic syndrome (NS) is characterized by severe proteinuria as a consequence of kidney glomerular injury due to podocyte damage. In vitro models mimicking in vivo characteristics are prerequisite resolve NS pathogenesis. The detailed characterization organoid podocytes resulting from hybrid culture protocol showed population that resembles adult and was superior compared with 2D counterparts, based on single-cell RNA sequencing, super-resolution imaging electron microscopy. this study,...
Abstract Horizontal gene transfer in bacteria is widely believed to occur via conjugation, transduction and transformation. These mechanisms facilitate the passage of DNA across protective cell wall using sophisticated machinery. Here, we report that wall-deficient can engulf other extracellular material an endocytosis-like process. Specifically, show L-forms filamentous actinomycete Kitasatospora viridifaciens take up plasmid DNA, polysaccharides (dextran) 150-nm lipid nanoparticles. The...
Abstract Cryo-correlative light and electron microscopy (cryoCLEM) is a powerful strategy to high resolution imaging in the unperturbed hydrated state. In this approach fluorescence aids localizing area of interest, cryogenic focused ion beam/scanning (cryoFIB/SEM) allows preparation thin cryo-lamellae for cryoET. However, current method cannot be accurately applied on bulky (3D) samples such as tissues organoids. 3D cryo-correlative large volumes needed close gap between cryo-light cryoET,...
Abstract Osteons, the main organizational components of human compact bone, are cylindrical structures composed layers mineralized collagen fibrils, called lamellae. These lamellae have different orientations, degrees organization, and mineralization where intrafibrillar extrafibrillar minerals intergrown into one continuous network oriented crystals. While cellular activity is clearly source organic matrix, recent in vitro studies call question whether cells also involved matrix suggest...
Abstract Liquid phase electron microscopy (LP‐EM) has emerged as a powerful technique for in situ observation of material formation liquid. Especially the use graphene window provides new opportunities to image biological processes because graphene's molecular thickness and scavenger capabilities. However, most cases process interest is initiated when liquid cells (GLCs) are sealed, meaning that cannot be imaged at early timepoints. Here, novel cryogenic/liquid correlative light/electron...
Aortic valve stenosis (AS), the leading valvular disease in aging populations, is driven by complex extracellular matrix (ECM) modifications and progressive calcification. Despite its clinical significance, molecular mechanisms underlying AS remain poorly understood, limiting therapeutic options to invasive replacement. This study employs Raman microscopy, a label-free imaging technique, integration with transmission electron microscopy (TEM) elucidate biochemical ultrastructural changes...