LINC complex-Lisl interplay controls MT1-MMP matrix digest-on-demand response for confined tumor cell migration

Cancer cells' ability to migrate through constricting pores in the tissue matrix is limited by nuclear stiffness. MT1-MMP contributes to metastasis by widening matrix pores, facilitating confined migration. Here, we show that modulation of matrix pore size or of lamin A expression known to modulate nuclear stiffness directly impinges on levels of MT1-MMP-mediated pericellular collagenolysis by cancer cells. A component of this adaptive response is the centrosome-centered distribution of MT1-MMP intracellular storage compartments ahead of the nucleus. We further show that this response, including invadopodia formation in association with confining matrix fibrils, requires an intact connection between the nucleus and the centrosome via the linker of nucleoskeleton and cytoskeleton (LINC) complex protein nesprin-2 and dynein adaptor Lis1. Our results uncover a digest-on-demand strategy for nuclear translocation through constricted spaces whereby confined migration triggers polarization of MT1-MMP storage compartments and matrix proteolysis in front of the nucleus depending on nucleus-microtubule linkage

The first World Cell Race

Motility is a common property of animal cells. Cell motility is required for embryogenesis [1], tissue morphogenesis [2] and the immune response [3] but is also involved in disease processes, such as metastasis of cancer cells [4]. Analysis of cell migration in native tissue in vivo has yet to be fully explored, but motility can be relatively easily studied in vitro in isolated cells. Recent evidence suggests that cells plated in vitro on thin lines of adhesive proteins printed onto culture dishes can recapitulate many features of in vivo migration on collagen fibers 5, 6. However, even with controlled in vitro measurements, the characteristics of motility are diverse and are dependent on the cell type, origin and external cues. One objective of the first World Cell Race was to perform a large-scale comparison of motility across many different adherent cell types under standardized conditions. To achieve a diverse selection, we enlisted the help of many international laboratories, who submitted cells for analysis. The large-scale analysis, made feasible by this competition-oriented collaboration, demonstrated that higher cell speed correlates with the persistence of movement in the same direction irrespective of cell origin

Preparation of novel optical fibre-based Cocaine sensors using a molecular imprinted polymer approach

Novel chemical sensors using fibre optic-based techniques for the detection of Cocaine have been developed, utilising molecularly imprinted polymers (MIPs) containing fluorescein moieties as the signalling groups. The fluorescent MIPs were formed and covalently attached to the distal end of specially chosen optical fibres to create fibre optic probe-based sensors. These sensors exhibited are producible and quantifiable change in the intensity of the fluorescence signal received from the sensor in response to Cocaine in aqueous acetonitrile mixtures. High selectivity for Cocaine over Codeine and a range of known Cocaine interferants has been demonstrated for one of the sensors developed in this work

Objective comparison of particle tracking methods

Particle tracking is of key importance for quantitative analysis of intracellular dynamic processes from time-lapse microscopy image data. Because manually detecting and following large numbers of individual particles is not feasible, automated computational methods have been developed for these tasks by many groups. Aiming to perform an objective comparison of methods, we gathered the community and organized an open competition in which participating teams applied their own methods independently to a commonly defined data set including diverse scenarios. Performance was assessed using commonly defined measures. Although no single method performed best across all scenarios, the results revealed clear differences between the various approaches, leading to notable practical conclusions for users and developers

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

In-vitro validation of 4D flow MRI measurements with an experimental pulsatile flow model

International audienceAbstract Purpose: The purpose of this study was to assess the precision of four-dimensional (4D) phase-contrast magnetic resonance imaging (PCMRI) to measure mean flow and peak velocity (V max) in a pulsatile flow phantom and to test its sensitivity to spatial resolution and Venc. Material and methods: The pulsatile flow phantom consisted of a straight tube connected to the systemic circulation of an experimental mock circulatory system. Four-dimensional-PCMR images were acquired using different spatial resolutions (minimum pixel size: 1.5 × 1.5 × 1.5 mm 3) and velocity encoding sensitivities (up to three times V max). Mean flow and V max calculated from 4D-PCMRI were compared respectively to the reference phantom flow parameters and to V max obtained from two-dimensional (2D)-PCMRI. Results: 4D-PCI measured mean flow with a precision of −0.04% to + 5.46%, but slightly underestimated V max when compared to 2D-PCMRI (differences ranging from −1.71% to −3.85%). 4D PCMRI mean flow measurement was influenced by spatial resolution (P < 0.001) with bette