Alignment of cell division axes in directed epithelial cell migration

Cell division is an essential dynamic event in tissue remodeling during wound healing, cancer and embryogenesis. In collective migration, tensile stresses affect cell shape and polarity, hence, the orientation of the cell division axis is expected to depend on cellular flow patterns. Here, we study the degree of orientation of cell division axes in migrating and resting epithelial cell sheets. We use microstructured channels to create a defined scenario of directed cell invasion and compare this situation to resting but proliferating cell monolayers. In experiments, we find a strong alignment of the axis due to directed flow while resting sheets show very weak global order, but local flow gradients still correlate strongly with the cell division axis. We compare experimental results with a previously published mesoscopic particle based simulation model. Most of the observed effects are reproduced by the simulations

Publisher Correction: Multi-experiment nonlinear mixed effect modeling of single-cell translation kinetics after transfection

The original version of this Article had an incorrect Article number of 1, an incorrect Volume of 5 and an incorrect Publication year of 2019. These errors have now been corrected in the PDF and HTML versions of the Article

Multi-experiment nonlinear mixed effect modeling of single-cell translation kinetics after transfection

Statistical inference: mixed effect modeling enables integration of single-cell data Single-cell time-lapse data provide a rich source of information on cellular pathways and cell-to-cell variability, yet, we lack statistical methods to extract this information. A team led by Joachim Rädler at the Ludwig-Maximilians-Universität München and Jan Hasenauer at the Helmholtz Zentrum München addressed this problem and demonstrated that mixed effect modeling enables a rigorous integration of single-cell data collected in different experiments. The experimental and computational study of mRNA transfection revealed that the use of mixed-effect models improves parameter identifiability and resolves symmetries, which are limitations of existing approaches. The proposed approach is widely applicable to single- cell time-lapse data and improves data exploitation. The in-depth assessment of single-cell dynamics will provide novel insights in disease progression and mRNA-based treatment options

Inter-laboratory comparison of nanoparticle size measurements using dynamic light scattering and differential centrifugal sedimentation

Nanoparticle in vitro toxicity studies often report contradictory results with one main reason being insufficient material characterization. In particular the characterization of nanoparticles in biological media remains challenging. Our aim was to provide robust protocols for two of the most commonly applied techniques for particle sizing, i.e. dynamic light scattering (DLS) and differential centrifugal sedimentation (DCS) that should be readily applicable also for users not specialized in nanoparticle physico-chemical characterization. A large number of participants (40, although not all participated in all rounds) were recruited for a series of inter-laboratory comparison (ILC) studies covering many different instrument types, commercial and custom-built, as another possible source of variation. ILCs were organized in a consecutive manner starting with dispersions in water employing well-characterized near-spherical silica nanoparticles (nominal 19 nm and 100 nm diameter) and two types of functionalized spherical polystyrene nanoparticles (nominal 50 nm diameter). At first each laboratory used their in-house established procedures. In particular for the 19 nm silica particles, the reproducibility of the methods was unacceptably high (reported results were between 10 nm and 50 nm). When comparing the results of the first ILC round it was observed that the DCS methods performed significantly worse than the DLS methods, thus emphasizing the need for standard operating procedures (SOPs). SOPs have been developed by four expert laboratories but were tested for robustness by a larger number of independent users in a second ILC (11 for DLS and 4 for DCS). In a similar approach another SOP for complex biological fluids, i.e. cell culture medium containing serum was developed, again confirmed via an ILC with 8 participating laboratories. Our study confirms that well-established and fit-for-purpose SOPs are indispensable for obtaining reliable and comparable particle size data. Our results also show that these SOPs must be optimized with respect to the intended measurement system (e.g. particle size technique, type of dispersant) and that they must be sufficiently detailed (e.g. avoiding ambiguity regarding measurand definition, etc.). SOPs may be developed by a small number of expert laboratories but for their widespread applicability they need to be verified by a larger number of laboratories.Accepted versio