Scientific publications

Despite decades of research, how mammalian cell size is controlled remains unclear because of the difficulty of directly measuring growth at the single-cell level. Here we report direct measurements of single-cell volumes over entire cell cycles on various mammalian cell lines and primary human cells. We find that, in a majority of cell types, the volume added across the cell cycle shows little or no correlation to cell birth size, a homeostatic behavior called “adder”. This behavior involves modulation of G1 or S-G2 duration and modulation of growth rate. The precise combination of these mechanisms depends on the cell type and the growth condition. We have developed a mathematical framework to compare size homeostasis in datasets ranging from bacteria to mammalian cells. This reveals that a near-adder behavior is the most common type of size control and highlights the importance of growth rate modulation to size control in mammalian cells.

Vimentin is a protein that has been linked to a large variety of pathophysiological conditions, including cataracts, Crohn’s disease, rheumatoid arthritis, HIV and cancer. Vimentin has also been shown to regulate a wide spectrum of basic cellular functions. In cells, vimentin assembles into a network of filaments that spans the cytoplasm. It can also be found in smaller, non-filamentous forms that can localise both within cells and within the extracellular microenvironment. The vimentin structure can be altered by subunit exchange, cleavage into different sizes, re-annealing, post-translational modifications and interacting proteins. Together with the observation that different domains of vimentin might have evolved under different selection pressures that defined distinct biological functions for different parts of the protein, the many diverse variants of vimentin might be the cause of its functional diversity. A number of review articles have focussed on the biology and medical aspects of intermediate filament proteins without particular commitment to vimentin, and other reviews have focussed on intermediate filaments in an in vitro context. In contrast, the present review focusses almost exclusively on vimentin, and covers both ex vivo and in vivo data from tissue culture and from living organisms, including a summary of the many phenotypes of vimentin knockout animals. Our aim is to provide a comprehensive overview of the current understanding of the many diverse aspects of vimentin, from biochemical, mechanical, cellular, systems biology and medical perspectives

Amphiphilic polymer-based drug delivery systems hold potential in enhancing pharmacokinetics and therapeutic efficacy due to their ability to simultaneously codeliver different drugs in a controlled manner. We propose here a facile method for synthesizing a new amphiphilic polymer, farnesylated glycol chitosan (FGC), which self-assembles into nanoparticles upon being dispersed in aqueous media. The characteristics of FGC nanoparticles, in particular the size, could be tuned in a range from 200 to 500 nm by modulating the degree of farnesylation and the pH and polymer concentration during particle preparation. Carrier capacity, release kinetics, and surface modification of the established system were investigated using different model compounds. The colloids were biocompatible and stable at biologically relevant pH values. The interactions between the carriers and human mucus were examined by multiple particle tracking, which revealed that ∼80% of the particles remain immobilized within the mucus matrix. These results postulate FGC as a versatile drug delivery platform.

Abstract Supramolecular gels made from 2D building blocks are emerging as one of the novel multifunctional soft materials for various applications. This study reports on a class of supramolecular nanosheet gels formed through a reversible self-assembly process involving both intramolecular folding and intermolecular self-assembly of poly[oligo(ethylene glycol)-co-(phenyl-capped bithiophenes)]. Such hierarchical self-assembled structure allows the gels to switch between sol and gel states under either redox or thermostimulus. Moreover, the gels illustrate high Young's moduli, compared to their controls that are made from the same oligo(ethylene glycol) and phenyl-capped bithiophenes blocks but have highly covalent-crosslinked structures. The example might open a window for emerging supramolecular 2D materials to develop mechanically robust and stimuli-responsive soft materials without compromising their intrinsic functions.

Developments in microscopy have been instrumental to progress in the life sciences, and many new techniques have been introduced and led to new discoveries throughout the last century. A wide and diverse range of methodologies is now available, including electron microscopy, atomic force microscopy, magnetic resonance imaging, small-angle x-ray scattering and multiple super-resolution fluorescence techniques, and each of these methods provides valuable read-outs to meet the demands set by the samples under study. Yet, the investigation of cell development requires a multi-parametric approach to address both the structure and spatio-temporal organization of organelles, and also the transduction of chemical signals and forces involved in cell–cell interactions. Although the microscopy technologies for observing each of these characteristics are well developed, none of them can offer read-out of all characteristics simultaneously, which limits the information content of a measurement. For example, while electron microscopy is able to disclose the structural layout of cells and the macromolecular arrangement of proteins, it cannot directly follow dynamics in living cells. The latter can be achieved with fluorescence microscopy which, however, requires labelling and lacks spatial resolution. A remedy is to combine and correlate different readouts from the same specimen, which opens new avenues to understand structure–function relations in biomedical research. At the same time, such correlative approaches pose new challenges concerning sample preparation, instrument stability, region of interest retrieval, and data analysis. Because the field of correlative microscopy is relatively young, the capabilities of the various approaches have yet to be fully explored, and uncertainties remain when considering the best choice of strategy and workflow for the correlative experiment. With this in mind, the Journal of Physics D: Applied Physics presents a special roadmap on the correlative microscopy techniques, giving a comprehensive overview from various leading scientists in this field, via a collection of multiple short viewpoints.

We report laser ablation experiments on polished 4H-SiC wafers using an 193 nm ArF laser over a fluence range of  mJ cm−2–5000 mJ cm−2. An onset of material modification was measured at a laser fluence of 925 ± 80 mJ cm−2, and a concomitant etch rate of ∼200 pm per pulse. Laser ablation sites have been analysed using optical microscopy, scanning electron microscopy, Raman microscopy and white light interferometry. Finite element simulations using COMSOL™ Metaphysics, 5.3 have been used to calculate laser induced temperature rise of 4H-SiC as a function of laser fluence. The laser fluence required to reach the melting points of silicon, silicon carbide and carbon have been calculated and correspond to ∼970, 1950, 2600 mJ cm−2 respectively. Two different surface modifications are observed. At a laser fluence in the region of 1.0 J cm−2 the irradiated site removed material forming a uniform crater. At a higher laser fluence, in the region of 2700 mJ cm−2, nodule-like structures form on the base of the ablation crater. The dissociation of laser irradiated 4H-SiC is briefly discussed.

Fundamental biological processes are carried out by curved epithelial sheets that enclose a pressurized lumen. How these sheets develop and withstand three-dimensional deformations has remained unclear. Here we combine measurements of epithelial tension and shape with theoretical modelling to show that epithelial sheets are active superelastic materials. We produce arrays of epithelial domes with controlled geometry. Quantification of luminal pressure and epithelial tension reveals a tensional plateau over several-fold areal strains. These extreme strains in the tissue are accommodated by highly heterogeneous strains at a cellular level, in seeming contradiction to the measured tensional uniformity. This phenomenon is reminiscent of superelasticity, a behaviour that is generally attributed to microscopic material instabilities in metal alloys. We show that in epithelial cells this instability is triggered by a stretch-induced dilution of the actin cortex, and is rescued by the intermediate filament network. Our study reveals a type of mechanical behaviour—which we term active superelasticity—that enables epithelial sheets to sustain extreme stretching under constant tension.

The study of the key parameters impacted surface-assisted laser desorption/ionization-mass spectrometry is of broad interest. In previous studies, it has been shown that surface-assisted laser desorption/ionization-mass spectrometry is a complex process depending on multiple factors. In the presented study, we showed that neither porosity, light absorbance nor surface hydrophobicity alone influence the enhancement phenomena observed from the hybrid metal-semiconductor complexes versus individual targets, but small changes in the analyte attaching to the target significantly affect laser desorption ionization-efficiency. By means of Raman spectroscopy and scanning electron microscopy, it was revealed that the formation of an amorphous analyte layer after drying on a solid substrate was essential for the enhanced laser desorption ionization-signal observed from the hybrid metal-semiconductor targets, and the crystallization properties of the analyte appeared as a function of the substrate. Obtained results were used for the screening of regular and lactose-free milk samples through the hybrid metal-semiconductor target. Copyright © 2016 John Wiley & Sons, Ltd.

The MicroJet reactor technique is an excellent continuous method to produce spherical and homogeneous organically modified silica (ORMOSIL) particles in a large scale (10-15 g min-1). We applied this method to manufacture polyorganosilsesquioxanes with different ratios of phenyl and vinyl functional groups, which were later pyrolyzed to obtain silicon oxycarbides. Such polymer-derived ceramic (PDC) materials are highly suited as precursor for carbide-derived carbon (CDC) synthesis. Chlorine etching of PDC at high temperatures removed silicon and oxygen, yielding the formation of nanoporous carbon. Pure poly(phenyl-silsesquioxane) spheres lost their shape during the thermal process by undergoing further condensation reactions. Yet, the spherical shape was conserved during thermal processing after adding vinyl functionalities. The ratio of vinyl and phenyl functionalities controlled the pore structure and the total CDC yield, enabling an increase from 2 mass% to 22 mass%. The total pore volume varied between 1.3-2.1 cm3 g-1 and the specific surface area between 2014-2114 m2 g-1. The high surface area and large pore volume makes these materials attractive for high power supercapacitor electrodes. The specific capacitance of the best sample at low rates in 1 M tetraethylammonium tetrafluoroborate in acetonitrile was 116 F g-1 (at 5 mA g-1) and still 80 F g-1 at very high rates (at 100 A g-1).

Water-soluble shape-persistent cyclodextrin (CD) polymers with amino-functionalized end groups were prepared starting from diacetylene-modified cyclodextrin monomers by a combined Glaser coupling/click chemistry approach. Structural perfection of the neutral CD polymers and inclusion complex formation with ditopic and monotopic guest molecules were proven by MALDI–TOF and UV–vis measurements. Small-angle neutron and X-ray (SANS/SAXS) scattering experiments confirm the stiffness of the polymer chains with an apparent contour length of about 130 Å. Surface modification of planar silicon wafers as well as AFM tips was realized by covalent bound formation between the terminal amino groups of the CD polymer and a reactive isothiocyanate–silane monolayer. Atomic force measurements of CD polymer decorated surfaces show enhanced supramolecular interaction energies which can be attributed to multiple inclusion complexes based on the rigidity of the polymer backbone and the regular configuration of the CD moieties. Depending on the geometrical configuration of attachment anisotropic adhesion characteristics of the polymer system can be distinguished between a peeling and a shearing mechanism.