Nuclear and Cellular Plasticity: Nuclear RAC1 Takes Center Stage

Navarro-Lérida et al. (2015) report in this issue of Developmental Cell that RAC1 nuclear accumulation causes actin-dependent deformation of the nuclear envelope and increases nuclear plasticity. It further leads to depletion of cytoplasmic, active RAC1 with a concomitant increase in RHOA signaling driving actomyosin-mediated cell shape changes. These two properties combine to enhance tumor cells invasiveness

The “endocytic matrix reloaded” and its impact on the plasticity of migratory strategies

Background and aims: Phenylalanine (Phe) restricted diet, combined with Phe-free L-amino acid supplementation, is the mainstay of treatment for phenylketonuria (PKU). Being the diet a key factor modulating gut microbiota composition, the aim of the present paper was to compare dietary intakes, gut An explosive growth in knowledge, in the last two decades, has conferred a new dimension to the process of endocytosis. Endocytic circuitries have come into focus as a pervasive system that controls virtual all aspects of cell biology. A few years ago, we proposed the term \u201cendocytic matrix\u201d to define a cellular network of signalling wiring that is at the core of the cellular blueprint. A primary role of the endocytic matrix is the delivery of space- and time-resolved signals to the cell in an interpretable format, and, as such, it has profound consequences on polarized cellular and supra-cellular functions, first and foremost, cell motility. Here, we describe a set of recent results that expand this notion and illuminate how endocytic matrix dynamically controls the plasticity of migratory strategies. We further highlight the impact of inter-organelle contact sites on motility and the role of organelle positioning in this process. Finally, we illustrate how global perturbation of the endocytic circuitry influences cellular and supra-cellular mechanics, ultimately controlling a solid-to-liquid-like transition in the mode of motility with potential consequences on cancer dissemination

Frustration induced phases in migrating cell clusters

Collective motion of cells is common in many physiological processes, including tissue development, repair, and tumor formation. Recent experiments have shown that certain malignant cancer cells form clusters in a chemoattractant gradient, which display three different phases of motion: translational, rotational, and random. Intriguingly, all three phases are observed simultaneously, with clusters spontaneously switching between these modes of motion. The origin of this behavior is not understood at present, especially the robust appearance of cluster rotations. Guided by experiments on the motion of two-dimensional clusters in-vitro, we developed an agent based model in which the cells form a cohesive cluster due to attractive and alignment interactions but with potentially different behaviors based on their local environment. We find that when cells at the cluster rim are more motile, all three phases of motion coexist, in excellent agreement with the observations. Using the model we can identify that the transitions between different phases are driven by a competition between an ordered rim and a disordered core accompanied by the creation and annihilation of topological defects in the velocity field. The model makes definite predictions regarding the dependence of the motility phase of the cluster on its size and external chemical gradient, which agree with our experimental data. Our results suggest that heterogeneous behavior of individuals, based on local environment, can lead to novel, experimentally observed phases of collective motion.Comment: 14 pages, 5 figure

The Role of Green and Blue Hydrogen in the Energy Transition - A Technological and Geopolitical Perspective

Hydrogen is currently enjoying a renewed and widespread momentum in many national and international climate strategies. This review paper is focused on analysing the challenges and opportunities that are related to green and blue hydrogen, which are at the basis of different perspectives of a potential hydrogen society. While many governments and private companies are putting significant resources on the development of hydrogen technologies, there still remains a high number of unsolved issues, including technical challenges, economic and geopolitical implications. The hydrogen supply chain includes a large number of steps, resulting in additional energy losses, and while much focus is put on hydrogen generation costs, its transport and storage should not be neglected. A low-carbon hydrogen economy offers promising opportunities not only to fight climate change, but also to enhance energy security and develop local industries in many countries. However, to face the huge challenges of a transition towards a zero-carbon energy system, all available technologies should be allowed to contribute based on measurable indicators, which require a strong international consensus based on transparent standards and targets

Tracking-Free Determination of Single-Cell Displacements and Division Rates in Confluent Monolayers

A biological tissue is an ensemble of soft cells in close physical contact. Events such as cell-shape changes and, more rarely, cell-divisions and apoptosis continuously occur in a tissue, whose collective behavior is set by the cumulative occurrence of such events. In this complex environment, quantifying the single-cell dynamics is key to extract quantitative information to be used to capture the fundamental ingredients of this collective tissue dynamics for validating the predictions of models and numerical simulations. However, tracking the motion of each cell in a dense assembly, even in controlled in vitro settings, is a demanding task, because of a combination of different factors, such as poor image quality, cell shape variability and cell deformability. Here we show that Differential Dynamic Microscopy (DDM), an approach that provides a characterization of the sample structure and dynamics at various spatial frequencies (wave-vectors), can be used successfully to extract quantitative information about a confluent monolayer of Madin-Darby Canine Kidney (MDCK) epithelial cells. In particular, combining structural and dynamical information obtained at different wave-vectors, we show that DDM can provide the single-cell mean squared displacement and the cell division rate at various stages during the temporal evolution of the monolayer. In contrast with tracking algorithms, which require expert supervision and a considerate choice of the analysis parameters, DDM analysis can be run in an automated fashion and yields an unbiased quantification of the dynamic processes under scrutiny, thus providing a powerful means to probe the single-cell dynamics within dense cell collectives

Giant fluctuations and structural effects in a flocking epithelium

We thank S Henkes for useful discussions. FGia and RC acknowledge funding from the Italian Ministry of University and Scientific Research (MIUR) under the program Futuro in Ricerca—Project ANISOFT (RBFR125H0M) and from Regione Lombardia and CARIPLO foundation under the joint action Avviso congiunto per l'incremento dell'attrattivitá del sistema ricerca lombardo e della competitivitá dei ricercatori candidati su strumenti ERC—Project 2016-0998. CM, SC and GS acknowledge funding from Associazione Italiana per la Ricerca sul Cancro (AIRC 10168 and 18621), MIUR, the Italian Ministry of Health, Ricerca Finalizzata (RF0235844), Worldwide Cancer Research (AICR-14-0335), and the European Research Council (Advanced-ERC-268836). CM was also supported by Fondazione Umberto Veronesi and SC by an AIRC fellowship. FGin acknowledges support from the Marie Curie Career Integration Grant (CIG) PCIG13-GA-2013-618399, and wish to thank the University of Milan and LibrOsteria for their hospitality while this work was underway.Peer reviewedPostprin

Bursts of activity in collective cell migration

Dense monolayers of living cells display intriguing relaxation dynamics, reminiscent of soft and glassy materials close to the jamming transition, and migrate collectively when space is available, as in wound healing or in cancer invasion. Here we show that collective cell migration occurs in bursts that are similar to those recorded in the propagation of cracks, fluid fronts in porous media and ferromagnetic domain walls. In analogy with these systems, the distribution of activity bursts displays scaling laws that are universal in different cell types and for cells moving on different substrates. The main features of the invasion dynamics are quantitatively captured by a model of interacting active particles moving in a disordered landscape. Our results illustrate that collective motion of living cells is analogous to the corresponding dynamics in driven, but inanimate, systems