Mechanosensing at integrin-mediated cell–matrix adhesions: from molecular to integrated mechanisms

Integrin-mediated adhesions between cells and the extracellular matrix are fundamental for cell function, and one of their main roles is to sense and respond to mechanical force. Here we discuss the different mechanisms that can confer mechanosensitivity to adhesions. We first address molecular mechanisms mediated by force-induced changes in molecular properties, such as binding dynamics or protein conformation. Then, we discuss recent evidence on how these mechanisms are integrated with cellular and extracellular parameters such as myosin and actin activity, membrane tension, and ECM properties, endowing cells with an exquisite ability to both detect and respond to physical and mechanical cues from their environment

Special issue “Swarm science results after 2 years in space”

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Physical principles of membrane remodelling during cell mechanoadaptation

Biological processes in any physiological environment involve changes in cell shape, which must be accommodated by their physical envelope-the bilayer membrane. However, the fundamental biophysical principles by which the cell membrane allows for and responds to shape changes remain unclear. Here we show that the 3D remodelling of the membrane in response to a broad diversity of physiological perturbations can be explained by a purely mechanical process. This process is passive, local, almost instantaneous, before any active remodelling and generates different types of membrane invaginations that can repeatedly store and release large fractions of the cell membrane. We further demonstrate that the shape of those invaginations is determined by the minimum elastic and adhesive energy required to store both membrane area and liquid volume at the cell-substrate interface. Once formed, cells reabsorb the invaginations through an active process with duration of the order of minutes

DiscoSnp-RAD: de novo detection of small variants for RAD-Seq population genomics

International audienceRestriction site Associated DNA Sequencing (RAD-Seq) is a technique characterized by the sequencing of specific loci along the genome that is widely employed in the field of evolutionary biology since it allows to exploit variants (mainly Single Nucleotide Polymorphism—SNPs) information from entire populations at a reduced cost. Common RAD dedicated tools, such as STACKS or IPyRAD, are based on all-vs-all read alignments, which require consequent time and computing resources. We present an original method, DiscoSnp-RAD, that avoids this pitfall since variants are detected by exploiting specific parts of the assembly graph built from the reads, hence preventing all-vs-all read alignments. We tested the implementation on simulated datasets of increasing size, up to 1,000 samples, and on real RAD-Seq data from 259 specimens of Chiastocheta flies, morphologically assigned to seven species. All individuals were successfully assigned to their species using both STRUCTURE and Maximum Likelihood phylogenetic reconstruction. Moreover, identified variants succeeded to reveal a within-species genetic structure linked to the geographic distribution. Furthermore, our results show that DiscoSnp-RAD is significantly faster than state-of-the-art tools. The overall results show that DiscoSnp-RAD is suitable to identify variants from RAD-Seq data, it does not require time-consuming parameterization steps and it stands out from other tools due to its completely different principle, making it substantially faster, in particular on large datasets

Growth, Productivity, Biomass and Carbon Stock in Eucalyptus saligna and Grevillea robusta Plantations in North Kivu, Democratic Republic of the Congo

peer reviewedInitiated by the World Wildlife Fund (WWF) more than a decade ago in North Kivu, sin- gle-species plantations of Eucalyptus saligna and Grevillea robusta constitute, with other village plantations, the current legal source of wood-energy for the communities bordering the Virunga National Park (PNVi). This study assesses the growth and productivity of these plantations in two sites with different soil and climatic conditions to predict their production over time. The study also assesses the carbon stock and long-term CO2 fixation in the biomass of the studied plantations to deduce their contribution to climate change mitigation. Non-destructive inventories were carried out during three consecutive years in 20 E. saligna and 12 G. robusta plantations in Sake and Kirumba. Analysis of the data revealed that both species have similar diametric growth while height growth and productivity were significantly higher in the E. saligna plantations. The productivity of E. saligna was also higher in Kirumba than in Sake, while that of G. robusta was higher in Sake than in Kirumba. The differences observed were mainly related to species, silviculture, altitude and concentration of bioavailable elements in the soils. The analysis of productivity evolution over time allowed us to determine optimal rotations at 8 and 12 years, respectively, for E. saligna and G. robusta plantations. The relationships between biomass or carbon stock and tree diameter were not different between the studied species but were significantly different at the stand level. If silviculture was standardized and plantations carefully monitored, carbon stock and long-term CO2 fixation would be higher in G. robusta plantations than in E. saligna plantations. These results indicate that while for productivity reasons E. saligna is the favoured species in wood-energy plantations to quickly meet the demand of the growing and disadvantaged population living in the vicinity of PNVi, carefully monitored G. robusta plantations could be more interesting in terms of carbon credits. To simultaneously optimise wood-energy production and carbon storage in the plantations initiated in North Kivu, E. saligna and G. robusta should be planted in mixture. In addition, species and site characteristics adapted silvicultural management practices must be applied to these plantations, which are very important for the region, its population and its park. Finally, the economic profitability as well as the sustainability of the plantations should be assessed in the longer term in North Kivu

F-actin dynamics regulates mammalian organ growth and cell fate maintenance.

BACKGROUND & AIMS: In vitro, several data indicate that cell function can be regulated by the mechanical properties of cells and of the microenvironment. Cells measure these features by developing forces via their actomyosin cytoskeleton, and respond accordingly by transducing forces into biochemical signals that instruct cell behavior. Among these, the transcriptional coactivators YAP/TAZ recently emerged as key factors mediating multiple responses to actomyosin contractility. However, whether mechanical cues regulate adult liver tissue homeostasis, and whether this occurs through YAP/TAZ, remains largely unaddressed. METHODS & RESULTS: Here we show that the F-actin capping protein CAPZ is a critical negative regulator of actomyosin contractility and mechanotransduction. Capzb inactivation alters stress fiber and focal adhesion dynamics leading to enhanced myosin activity, increased cellular traction forces, and increased liver stiffness. In vitro, this rescues YAP from inhibition by a small geometry; in vivo, inactivation of Capzb in the adult mouse liver induces YAP activation in parallel to the Hippo pathway, causing extensive hepatocyte proliferation and leading to striking organ overgrowth. Moreover, Capzb is required for the maintenance of the differentiated hepatocyte state, for metabolic zonation, and for gluconeogenesis. In keeping with changes in tissue mechanics, inhibition of the contractility regulator ROCK, or deletion of the Yap1 mechanotransducer, reverse the phenotypes emerging in Capzb-null livers. CONCLUSIONS: These results indicate a previously unrecognized role for CAPZ in tuning the mechanical properties of cells and tissues, which is required in hepatocytes for the maintenance of the differentiated hepatocyte state and to regulate organ size. More in general, it indicates for the first time a physiological role of mechanotransduction in maintaining tissue homeostasis in mammals. LAY SUMMARY: The mechanical properties of cells and tissues (i.e. whether they are soft or stiff) are thought to be important regulators of cell behavior. A recent advancement in our understanding of these phenomena has been the identification of YAP and TAZ as key factors mediating the biological responses of cells to mechanical signals in vitro. However, whether the mechanical properties of cells and/or the mechanical regulation of YAP/TAZ are relevant for mammalian tissue physiology remains unknown. Here we challenge this issue by genetic inactivation of CAPZ, a protein that regulates the cytoskeleton, i.e. the cells' scaffold by which they sense mechanical cues. We found that inactivation of CAPZ alters cells' and liver tissue's mechanical properties, leading to YAP hyperactivation. In turn, this profoundly alters liver physiology, causing organ overgrowth, defects in liver cell differentiation and metabolism. These results reveal a previously uncharacterized role for mechanical signals for the maintenance of adult liver homeostasis.This work was supported by AIRC (Associazione Italiana per la Ricerca sul Cancro) Investigator Grant 15307, WCR (Worldwide Cancer Research) Grant 15-1192, CARIPARO Eccellenza Program 2017 and University of Padua BIRD Grant to SD, AIRC ‘Hard ROCK Café’ Fellowship to GS, Marie Sklodowska-Curie Individual Fellowship (796547) to AG, AIRC Special Program Molecular Clinical Oncology ‘5 per mille’ 10016 to SB, UK Medical Research Council and Sackler Foundation Doctoral Training Grant RG70550 to ACL, UK Medical Research Council Career Development Award G1100312/1 and an Isaac Newton Trust Research Grant 17.24(p) to KF