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📰 "Influence of erythrocyte density on aggregability as a marker of cell age: Dissociation dynamics in extensional flow"
arxiv.org/abs/2409.08877 #Physics.Bio-Ph #Mechanical #Dynamics #Cell

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arXiv.orgInfluence of erythrocyte density on aggregability as a marker of cell age: Dissociation dynamics in extensional flowBlood rheology and microcirculation are strongly influenced by red blood cell (RBC) aggregation. The aggregability of RBCs can vary significantly due to factors such as their mechanical and membrane surface properties, which are affected by cell aging in vivo. In this study, we investigate RBC aggregability as a function of their density, a marker of cell age and mechanical properties, by separating RBCs from healthy donors into different density fractions using Percoll density gradient centrifugation. We examine the dissociation rates of aggregates in a controlled medium supplemented with Dextran, employing an extensional flow technique based on hyperbolic microfluidic constrictions and image analysis, assisted by a convolutional neural network (CNN). In contrast to other techniques, our microfluidic experimental approach highlights the behavior of RBC aggregates in dynamic flow conditions relevant to microcirculation. Our results demonstrate that aggregate dissociation is strongly correlated with cell density and that aggregates formed from the denser fractions of RBCs are significantly more robust than those from the average cell population. This study provides insight into the effect of RBC aging in vivo on their mechanical properties and aggregability, underscoring the importance of further exploration of RBC aggregation in the context of cellular senescence and its potential implications for hemodynamics. Additionally, it suggests that this technique can complement existing methods for improved evaluation of RBC aggregability in health and disease.

📰 "Extending the range of sizes of monodisperse core-shell hydrogel capsules from composite jet breakup by combined electrical and mechanical actuation"
arxiv.org/abs/2503.21333 #Physics.Flu-Dyn #Mechanical #Cell

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arXiv.orgExtending the range of sizes of monodisperse core-shell hydrogel capsules from composite jet breakup by combined electrical and mechanical actuationThe production of monodisperse particles or droplets is a longstanding issue across various fields, from aerosol science to inkjet printing. In bioengineering, submillimeter cell laden hydrogel capsules have proven valuable for developing in vitro tissue models. A common practical approach for producing such droplets relies on the Plateau Rayleigh instability to break up a liquid compound jet in air. However, while the droplet size is closely linked to nozzle dimensions, achieving high monodispersity suitable for quantitative biological assays remains challenging due to coalescence events associated with the beads on a string morphology of viscoelastic jets. Here, a microfluidic strategy is introduced, combining electrical and mechanical actuation to enhance control and versatility over jet breakup. By fine tuning the excitation frequency to select specific modes and applying an electric potential to regulate coalescence, a phase diagram is established, enabling the generation of monodisperse droplets over a broad size range. Notably, a previously hidden effect of the electric field on jet behavior is uncovered and quantitatively characterized. Finally, after crosslinking the compound droplets, capsules with a hydrogel envelope and a core composed of a cell suspension are formed in conditions compatible with cell proliferation, which lay the groundwork for quantitative high precision biological assays.

📰 "Prostate cancer associated fibroblasts have distinct morphomechanical features that are associated with patient outcome"
biorxiv.org/content/10.1101/20 #Mechanical #Cell

bioRxiv · Prostate cancer associated fibroblasts have distinct morphomechanical features that are associated with patient outcomeTumour development and progression reshape the physical properties of the surrounding tumour microenvironment (TME) including its biomechanical traits. This is driven by a prominent cell type in the TME, cancer associated fibroblasts (CAFs), which increases tissue stiffness via extracellular matrix deposition and remodelling. Currently, it is unclear whether there are also physical changes to CAFs at the cellular level and, if so, how they relate to patient outcome. Here we show that CAFs have distinct morphological and biomechanical features from normal fibroblasts. We examined matched, patient-derived CAFs and non-malignant prostate fibroblasts (NPFs) from 35 patients with primary prostate cancer. Morphologically, CAFs had more aligned stress fibres, and larger and more elongated nuclei, based on quantitative image analysis of confocal microscopy images. In addition, single-cell mechanical measurements using real-time deformability cytometry showed that CAFs are larger and stiffer than NPFs. These changes were consistent across patients and validated with atomic force microscopy. A combined morphomechanical score encompassing these features was significantly associated with patient outcome. In transcriptomic analyses, the score was correlated with microtubule dynamics and a myofibroblast phenotype. Importantly, we also demonstrated that morphomechanical features of prostate fibroblasts are modified by approved treatments for prostate cancer, such as docetaxel, and other small molecular inhibitors, such as axitinib. In summary, changes in cellular morphomechanical properties are a consistent feature of CAFs and associated with patient outcome. Moreover, cellular morphomechanical properties can be therapeutically targeted, potentially providing a new strategy for manipulating the TME to control cancer progression. ### Competing Interest Statement The authors have declared no competing interest.

📰 "Reduced gap junction coupling amplifies the effects of cardiomyocyte variability and destabilizes the heartbeat"
biorxiv.org/content/10.1101/20 #Mechanical #Cell

bioRxiv · Reduced gap junction coupling amplifies the effects of cardiomyocyte variability and destabilizes the heartbeatCardiomyocytes exhibit significant cell-to-cell variability due to differences in protein expression and post-translational modifications in both the cell membrane and the intracellular machinery. Resulting variability in action potential propagation and configuration have been proposed to promote arrhythmia. However, such effects may be suppressed by tight electrical coupling of cells in the healthy heart, but not during pathological conditions where gap junction function is impaired. To investigate this question, we employed a cell-based mathematical model of cardiac electrophysiology, in which we systematically modified both the properties of individual cells within the array, and inter-cellular electrical connectivity (gap junctions). Despite the inclusion of marked variation in properties between cells, we observed electrical homogeneity across the array when cells were well coupled. In contrast, lower and/or more variable gap junction connectivity resulted in nonhomogeneous action potential configuration, and irregular timing of both the depolarizing and repolarizing electrical wavefronts. Pro-arrhythmic early after-depolarizations also occurred under these conditions, linked to reopening of L-type calcium channels. These effects were effectively dampened in highly coupled cells. Nevertheless, baseline differences in calcium homeostasis were not negated by gap junction coupling, indicating a limit to which electrical connections can homogenize mechanical function. There are also physical limits to electrical convergence, as we observed that action potential differences persisted at the edges and corners of the array where there are fewer electrical contacts with neighbouring cells. This finding may have implications for arrhythmic susceptibility in the border zone neighbouring an infarction. In summary, our findings underscore the critical role of intercellular coupling in maintaining cardiac stability and highlight the importance of studying cardiomyocytes within a syncytium rather than in isolation. ### Competing Interest Statement The authors have declared no competing interest.

📰 "Acute high-dose irradiation of human primary ovarian cells reveals a shift in transcriptomics profile and impairment in cell-cell adhesion"
biorxiv.org/content/10.1101/20 #Mechanical #Cell

bioRxiv · Acute high-dose irradiation of human primary ovarian cells reveals a shift in transcriptomics profile and impairment in cell-cell adhesionSTUDY QUESTION: How do human cortical (cPOCs) and medullary (mPOCs) primary ovarian cells respond to acute X-ray exposure? SUMMARY ANSWER: Acute high-dose X-ray exposure causes a shift in cPOCs and mPOCs transcriptomic profiles and impairs significantly their cell-cell adhesion ability. WHAT IS KNOWN ALREADY: Radiotherapy is a leading cancer treatment, due to its effectiveness in targeting malignant cells. However, it can also affect healthy cells, potentially causing organ dysfunction, among which ovaries. When targeted radiotherapy is not feasible, fertility preservation is recommended to avoid premature ovarian insufficiency. In addition, the effects of irradiation on ovarian somatic cells remain poorly understood. STUDY DESIGN, SIZE, DURATION: Ovarian tissue was obtained from patients undergoing gender-affirming surgery at Karolinska University Hospital Huddinge, Sweden. The ovarian tissue was separated into cortex and medulla, then individually dissociated into single-cell suspensions using mechanical and enzymatic methods. Monolayer cultures from cPOCs and mPOCs were exposed to a single dose of 10 Gy X-ray irradiation or left unexposed as paired controls. Following irradiation, the cells were cultured at various time-points for further molecular and morphological evaluation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian tissue from 8 patients (age 23-36 years) was used. Dissociated cPOCs and mPOCs were cultured to 80% confluence and irradiated with 10 Gy (1.33 Gy/min), with non-irradiated controls. Cellular ATP and mitochondrial activity were assessed, followed by immunofluorescence staining for canonical irradiation-induced effects in cells: DNA damage, apoptosis and cell cycle progression. Bulk RNA-sequencing was performed on controls and irradiated samples. Libraries were prepared using the Illumina Stranded mRNA Prep Ligation protocol and sequenced on Illumina NovaSeq6000 platform. Genes were considered to be differentially expressed under the cut-off of false discovery rate (FDR) < 0.05. Subsequently, affected biological pathway was predicted using all expressed genes ranked by log2 fold change again hallmark gene sets. To further investigate the potential upstream regulators, transcription factor enrichment analysis were performed based on DEGs. To assess changes at protein level, we mapped the proteomic profile using liquid chromatography-tandem mass spectrometry. Peptides were considered to be differentially expressed (DEPs) under the cut-off of p-value < 0.01. Finally, we measured the ability of cPOCs and mPOCs to form 3D aggregates after seeding irradiated and non-irradiated cells on Biosilk scaffolds. MAIN RESULTS AND THE ROLE OF CHANCE: Following irradiation, ATP levels and mitochondrial activity in cPOCs and mPOCs were comparable to controls, indicating minimal irradiation impact on cell viability and proliferation. Immunofluorescence analysis confirmed the modulation of canonical pathways, such as DNA damage, apoptosis and cell cycle in both cPOCs and mPOCs. Transcriptomic analysis showed that cPOCs and mPOCs at 1 h post-irradiation clustered together with the related 1 h control. However, a shift in transcriptomic profile was observed after 4 h and even more after 24 h post-irradiation in both cPOCs and mPOCs. Gene set enrichment analysis (GSEA) indicated upregulation of the p53 pathway at 4 h and 24 h post-irradiation, alongside downregulation of MYC targets, E2F targets, the G2/M checkpoint and mTORC1 pathway. Gene pattern analysis showed irradiation-dependent trends related to extracellular matrix (ECM) organisation, p53-mediated apoptotic mechanisms and chromosome segregation during the 24 h period following irradiation. Additionally, transcription factor enrichment analysis based on DEGs suggested p53 and MYC as potential upstream regulators. On a proteomic level, DEPs associated with ECM organisation and cytoskeleton formation were detected at 4 and 24 h post-irradiation. Finally, X-ray exposure hindered the cell-cell adhesion ability of both cPOCs and mPOCs, leading to impaired formation of Silk-Ovarioids. LARGE SCALE DATA: The RNA sequencing count matrix is deposited in Gene Expression Omnibus (GEO) with accession number GSE291604. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD061796. The code used for the analysis can be found at https://github.com/tialiv/X-Ovary. LIMITATIONS, REASONS FOR CAUTION: The ovarian tissue was obtained from gender-affirming surgery patients who received androgen treatment before removal. Even though unlikely, this hormonal treatment might influence ovarian environment and alter cellular response to irradiation. Additionally, in this study the impact of X-ray exposure was assessed on a monolayer cell model, thus limiting the extrapolation power of our results to ovary in vivo. Lastly, the impact of irradiation was focused on the somatic cell populations that are essential for ovarian function. Further studies are needed to investigate the effects of X-ray exposure on ovarian follicles and their function. WIDER IMPLICATIONS OF THE FINDINGS: Understanding the roles of MYC, p53 and cell adhesion factors in response to irradiation could guide the development of future ovarian protective strategies. These findings lay the foundation for further studies on ovarian tissue protection and fertility preservation in cancer patients. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the European Union's HORIZON 2020 research and innovation programme (MATER) under the Marie Sklodowska-Curie Actions (grant agreement No: 813707), the Estonian Research Council (grants PRG1076 and PSG608), the Orion Research Foundation sr personal grant, the Research grant from the Center for Innovative Medicine (CIMED) and the Karolinska Institutet Consolidator Grant. ### Competing Interest Statement The authors have declared no competing interest.
animalis lucivoris, hey.

- composants électroniques, cuivre, plexiglas, bois - 2022

Balise lumineuse émettant "hey" en code morse après avoir accumulé suffisamment d'énergie ; alimentation par panneau solaire (si besoin par pile bouton).

Light marker which blinks "hey" in morse code after having stored enough energy ; power supply by solar cell (if necessary, by button cell).

#electronic #pcb #transistor #photovoltaic #cell #standalone #lowenergy #storage #morse #code #light #blink #hey #useless #device
#art #techart #lyon #ap22