Single‐Cell Quantification of Viscoelastic Phase Transitions in 3D Tissues

Advanced Materials Technologies, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Abstract Transitions of biological tissues between solid‐like and liquid‐like phases have been great recent interest. Here, the first successful cell‐by‐cell evaluation tissue viscoelastic transition is presented. An in situ micro‐mechanical perturbation applied to a microtissue, resulting volumetric deformation evaluated using 3D light‐sheet microscopy digital image correlation (DIC), quantifying both solid‐like, well‐aligned displacement swirling motion individual cells. The fibroblasts crucial fundamental physiological events, such as placentation, cancer dissemination, wound healing. This study investigates organoid systems modeling maternal‐fetal tumor‐stroma interfaces, demonstrating established molecular structural parallels. analysis visualizes cells stromal‐epithelial interactions how they collectively alter properties. It also enables in‐silico microdissection, linking single‐cell viscoelasticity with multi‐channel fluorescence. RNAseq endometrial stromal shows that decidualization activates mechano‐transcriptional regulators, including myocardin‐related transcription factors (MRTFs), associated increased cellular contractility actomyosin mobilization. Knocking down MRTFA cancer‐associated tumor‐fibroblast co‐culture model induces significant changes fibroblast properties, mirroring those observed interface model, highlighting parallels placentation invasion. confirms existing beliefs discovers new insights broadly applicable studying organoids, embryos, tumors, other tissues.

Language: Английский

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Cell spheroid micromechanics under large deformations

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: June 5, 2025

Mechanically characterizing biological tissues at the microscale helps to better link biomechanics mechanobiology but also contributes mechanistic understanding of disease mechanobiology. Cell spheroids (CSs) are state-of-the-art in vitro three-dimensional cell cultures allowing for synthesis microtissue models into sphere-like geometry. Such a geometry is attractive micromechanical assessment via parallel-plate compression, since only minimal and nondestructive sample preparation required conduct such tests. However, appropriate data analysis interpretation methods mostly lacking. Current approaches, relying on Hertzian theory its modifications, inadequate capturing large deformations observed CSs upon compression. Here, we utilized extended Tatara model, incorporating hyperelasticity nonlinear boundary effects, investigate CS mechanics. To evaluate effectiveness compared results Hertz, Ding, simple models. The model demonstrated superior accuracy, enabling mechanical under compression up 50% strain. Estimating apparent Poisson's ratio image segmentation shape helped refine calculated modulus. This work establishes robust analytical framework that will, future, help advance our cardiac fibrosis progression support development therapeutic strategies using patient-derived as test

Language: Английский

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i-Rheo-optical assay: Measuring the viscoelastic properties of multicellular spheroids

Materials Today Bio, Journal Year: 2024, Volume and Issue: 26, P. 101066 - 101066

Published: April 21, 2024

This study introduces a novel mechanobiology assay, named "i-Rheo-optical assay", that integrates rheology with optical microscopy for analysing the viscoelastic properties of multicellular spheroids. These spheroids serve as three-dimensional models resembling tissue structures. The innovative technique enables real-time observation and quantification morphological responses to applied stress using cost-effective microscope coverslip constant compression force application. By bridging knowledge gap in biophysical research, which has predominantly focused on elastic while only minimally exploring nature systems, i-Rheo-optical assay emerges an effective tool. It facilitates measurement broadband compressional moduli spheroids, here derived from cancer (PANC-1) non-tumoral (NIH/3T3) cell lines during tests. approach plays crucial role elucidating mechanical holds potential identifying biomarkers discriminate between healthy tissues their pathological counterparts. Offering comprehensive insights into biomechanical behaviour biological marks significant advancement engineering, therapeutic development.

Language: Английский

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The morphology of cell spheroids in simple shear flow

Frontiers in Physics, Journal Year: 2024, Volume and Issue: 12

Published: June 12, 2024

Cell spheroids are a widely used model to investigate cell-cell and cell-matrix interactions in 3D microenvironment vitro . Most research on cell has been focused their response various stimuli under static conditions. Recently, the effect of flow investigated context tumor invasion interstitial space. In particular, microfluidic perfusion embedded collagen matrix shown modulate adhesion represent possible mechanism promoting by flow. However, studies effects well-defined fields lacking literature. Here, we apply simple shear parallel plate apparatus while observing morphology optical microscopy. By using image analysis techniques, show that rotate as rigid prolate ellipsoids. As time goes on, cells from outer layer detach sheared carried away Hence, size declines with at rate increasing external stress, which can be estimate adhesion. The technique proposed this work allows one correlate flow-induced microscopy imaging well-established field, thus providing method obtain quantitative results relevant general field mechanobiology.

Language: Английский

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Linking Metastatic Potential and Viscoelastic Properties of Breast Cancer Spheroids via Dynamic Compression and Relaxation in Microfluidics

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 14, 2024

Abstract The growth and invasion of solid tumors are associated with changes in their viscoelastic properties, influenced by both internal cellular factors physical forces the tumor microenvironment. Due to lack a comprehensive investigation tissue viscoelasticity, relationship between such properties cancer malignancy remains poorly understood. Here, breast spheroids, 3D (in vitro) models, studied relation metastatic potentials imposing controlled, dynamic compression within microfluidic constriction, subsequently monitoring relaxation imposed deformation. By adopting modified Maxwell model extract from data, benign (MCF‐10A) spheroids found have higher bulk elastic modulus viscosity compared malignant (MCF‐7 MDA‐MB‐231). is characterized two timescales, captured double exponential fitting function, which reveals similar fast rebound for MCF‐7 MCF‐10A. Both exhibit long‐term display residual However, they differ significantly morphology, particularly intercellular movements. These differences demonstrated be linked cytoskeletal organization, microscopic imaging F‐actin together cell‐cell adhesion strength.

Language: Английский

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Linking metastatic potential and viscoelastic properties of breast cancer spheroids via dynamic compression and relaxation in microfluidics

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 24, 2024

The growth and invasion of solid tumors are associated with changes in their viscoelastic properties, influenced by both internal cellular factors physical forces the tumor microenvironment. Due to lack a comprehensive investigation tissue viscoelasticity, relationship between such properties cancer malignancy remains poorly understood. Here, breast spheroids, 3D ( vitro ) models, studied relation metastatic potentials imposing controlled, dynamic compression within microfluidic constriction, subsequently monitoring relaxation imposed deformation. By adopting modified Maxwell model extract from data, benign (MCF-10A) spheroids found have higher bulk elastic modulus viscosity compared malignant (MCF-7 MDA-MB-231). is characterized two timescales, captured double exponential fitting function, which reveals similar fast rebound for MCF-7 MCF-10A. Both exhibit long-term display residual However, they differ significantly morphology, particularly intercellular movements. These differences demonstrated be linked cytoskeletal organization, microscopic imaging F-actin together cell-cell adhesion strength.

Language: Английский

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