by Keyword: deformability
Conti, Sefora, Venturini, Valeria, Canellas-Socias, Adria, Cortina, Carme, Abenza, Juan F, Attolini, Camille Stephan-Otto, Guerra, Emily Middendorp, Xu, Catherine K, Li, Jia Hui, Rossetti, Leone, Stassi, Giorgio, Roca-Cusachs, Pere, Diz-Munoz, Alba, Ruprecht, Verena, Guck, Jochen, Batlle, Eduard, Labernadie, Anna, Trepat, Xavier, (2024). Membrane to cortex attachment determines different mechanical phenotypes in LGR5+and LGR5-colorectal cancer cells Nature Communications 15, 3363 
Colorectal cancer (CRC) tumors are composed of heterogeneous and plastic cell populations, including a pool of cancer stem cells that express LGR5. Whether these distinct cell populations display different mechanical properties, and how these properties might contribute to metastasis is poorly understood. Using CRC patient derived organoids (PDOs), we find that compared to LGR5- cells, LGR5+ cancer stem cells are stiffer, adhere better to the extracellular matrix (ECM), move slower both as single cells and clusters, display higher nuclear YAP, show a higher survival rate in response to mechanical confinement, and form larger transendothelial gaps. These differences are largely explained by the downregulation of the membrane to cortex attachment proteins Ezrin/Radixin/Moesin (ERMs) in the LGR5+ cells. By analyzing single cell RNA-sequencing (scRNA-seq) expression patterns from a patient cohort, we show that this downregulation is a robust signature of colorectal tumors. Our results show that LGR5- cells display a mechanically dynamic phenotype suitable for dissemination from the primary tumor whereas LGR5+ cells display a mechanically stable and resilient phenotype suitable for extravasation and metastatic growth. The mechanical properties of heterogeneous cell populations in colorectal tumors and the relevance to cancer metastasis remain not fully understood. Here, the authors suggest that the variations in malignant phenotypes between LGR5-positive cancer stem cells and LGR5-negative cells could be due to their distinct mechanical phenotypes observed in vitro, determined by the membrane to cortex attachment proteins Ezrin/Radixin/Moesin.
JTD Keywords: , , Adhesion, Deformability, E-cadherin, Erm proteins, Expression, Metastasis, Organization, Plasticit, Stem-cells, Tumor-cells
Mencattini, A, Rizzuto, V, Antonelli, G, Di Giuseppe, D, D'Orazio, M, Filippi, J, Comes, MC, Casti, P, Corrons, JLV, Garcia-Bravo, M, Segovia, JC, Manu-Pereira, MD, Lopez-Martinez, MJ, Samitier, J, Martinelli, E, (2023). Machine learning microfluidic based platform: Integration of Lab-on-Chip devices and data analysis algorithms for red blood cell plasticity evaluation in Pyruvate Kinase Disease monitoring Sensors And Actuators A-Physical 351, 114187
Microfluidics represents a very promising technological solution for conducting massive biological experiments. However, the difficulty of managing the amount of information available often precludes the wide potential offered. Using machine learning, we aim to accelerate microfluidics uptake and lead to quantitative and reliable findings. In this work, we propose complementing microfluidics with machine learning (MLM) approaches to enhance the diagnostic capability of lab-on-chip devices. The introduction of data analysis methodologies within the deep learning framework corroborates the possibility of encoding cell morphology beyond the standard cell appearance. The proposed MLM platform is used in a diagnostic test for blood diseases in murine RBC samples in a dedicated microfluidics device in flow. The lack of plasticity of RBCs in Pyruvate Kinase Disease (PKD) is measured massively by recognizing the shape deformation in RBCs walking in a forest of pillars within the chip. Very high accuracy results, far over 85 %, in recognizing PKD from control RBCs either in simulated and in real experiments demonstrate the effectiveness of the platform.
JTD Keywords: Blood disease, Deep transfer learning, Deficiency, Deformability, Machine learning microfluidics, Video analysis
Elosegui-Artola, A, (2021). The extracellular matrix viscoelasticity as a regulator of cell and tissue dynamics Current Opinion In Cell Biology 72, 10-18
The extracellular matrix mechanical properties regulate processes in development, cancer, and fibrosis. Among the distinct mechanical properties, the vast majority of research has focused on the extracellular matrix's elasticity as the primary determinant of cell and tissue behavior. However, both cells and the extracellular matrix are not only elastic but also viscous. Despite viscoelasticity being a universal feature of living tissues, our knowledge of the influence of the extracellular matrix's viscoelasticity in cell behavior is limited. This mini-review describes some of the recent findings that have highlighted the role of the extracellular matrix's viscoelasticity in cell and tissue dynamics.
JTD Keywords: behavior, cell adhesion, cell mechanics, cell migration, deformability, extracellular matrix, extracellular matrix mechanics, fluidity, forces, hydrogels, mechanobiology, mechanotransduction, tissue mechanics, viscoelasticity, viscosity, Cell adhesion, Cell mechanics, Cell migration, Extracellular matrix, Extracellular matrix mechanics, Fluidity, Mechanobiology, Mechanotransduction, Migration, Tissue mechanics, Viscoelasticity, Viscosity
