Generation of fate patterns via intercellular forces

Physical Review Research, Год журнала: 2025, Номер 7(2)

Опубликована: Июнь 4, 2025

Studies of fate patterning during development typically emphasize cell-cell communication via diffusible chemical signals. Recent experiments on stem cell colonies, however, suggest that in some cases mechanical stresses, rather than secreted chemicals, enable long-ranged interactions specify positional information and pattern fates. These findings inspire a model patterning: affects contractility, pressure the layer biases fate. Cells at colony edge, more contractile cells center, seed propagates force transmission. Strikingly, our implies width outer domain varies nonmonotonically with substrate stiffness, prediction we confirm experimentally; argue similar dependence stiffness can be achieved by morphogen only if strong constraints signaling pathway's mechanobiology are met. Our thus support idea stress mediate complete absence morphogens, even nonmotile layers, expanding repertoire possible roles for signals morphogenesis. Future tests additional predictions, like effect anisotropic rigidity, will further broaden range achievable patterns. Published American Physical Society 2025

Язык: Английский

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Receptor–Ligand Binding: Effect of Mechanical Factors

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(10), С. 9062 - 9062

Опубликована: Май 21, 2023

Gaining insight into the in situ receptor–ligand binding is pivotal for revealing molecular mechanisms underlying physiological and pathological processes will contribute to drug discovery biomedical application. An important issue involved how responds mechanical stimuli. This review aims provide an overview of current understanding effect several representative factors, such as tension, shear stress, stretch, compression, substrate stiffness on binding, wherein implications are focused. In addition, we highlight importance synergistic development experimental computational methods fully further studies should focus coupling effects these factors.

Язык: Английский

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Attenuating Epithelial‐to‐Mesenchymal Transition in Cancer through Angiopoietin‐Like 4 Inhibition in a 3D Tumor Microenvironment Model

Advanced Healthcare Materials, Год журнала: 2023, Номер 13(10)

Опубликована: Ноя. 21, 2023

Epithelial-to-mesenchymal transition (EMT) plays a crucial role in metastatic cancer progression, and current research, which relies heavily on 2D monolayer cultures, falls short recapitulating the complexity of 3D tumor microenvironment. To address this limitation, transcriptomic meta-analysis is conducted diverse types undergoing EMT cultures. It found that mechanotransduction elevated cultures further intensified during EMT, but not EMT. This analysis reveals distinct gene signature, characterized by extracellular matrix remodeling coordinated angiopoietin-like 4 (Angptl4) along with other canonical regulators. Utilizing hydrogel-based matrices adjustable mechanical forces, are established at varying physiological stiffness levels. A YAP:EGR-1 mediated up-regulation Angptl4 expression observed, accompanied an upregulation mesenchymal markers, higher Suppression using antisense oligonucleotides or anti-cAngptl4 antibodies leads to dose-dependent abolishment EMT-mediated chemoresistance self-organization 3D, ultimately resulting diminished potential stunted growth xenografts. unique programmable simulate levels microenvironment unveil as promising therapeutic target inhibit impede progression.

Язык: Английский

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Human alveolar hydrogels promote morphological and transcriptional differentiation in iPSC-derived alveolar type 2 epithelial cells

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Июль 25, 2023

Abstract Alveolar type 2 epithelial cells (AT2s) derived from human induced pluripotent stem (iAT2s) have rapidly contributed to our understanding of AT2 function and disease. However, while iAT2s are primarily cultured in three-dimensional (3D) Matrigel, a matrix cancerous mouse tissue, it is unclear how physiologically relevant will impact phenotype. As extracellular (ECM) recognized as vital component directing cellular differentiation, we sought derive hydrogels decellularized lung alveolar-enriched ECM (aECM) provide an ex vivo model characterize the role on iAT2 We demonstrate aECM retain critical situ components, including structural basement membrane proteins. While facilitate proliferation alveolosphere formation, subset change morphology thin elongated ring-like cells. This morphological correlates with upregulation recently described iAT2-derived transitional cell state genetic markers. such, potentially underappreciated differentiation.

Язык: Английский

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Biomechanical regulation of cell shapes promotes branching morphogenesis of the ureteric bud epithelium

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 31, 2024

Abstract Background Branching morphogenesis orchestrates organogenesis in many tissues including kidney, where ureteric bud branching determines kidney size and nephron number. Defects result congenital renal anomalies which manifest as deviations size, function, number thus critically compromising the lifelong functional capacity established during development. Advances genetic molecular understanding of regulation have proved insufficient to improve prognosis defects. Thus, we addressed mechanisms regulating three-dimensional (3D) epithelial cell morphology shape changes novel branch initiation uncover contributions cellular mechanics on functions tissue organization normal branching-compromised tips. Methods We explored behavior at all scales by utilizing a combination mouse genetics custom machine-learning segmentation pipeline MATLAB. Ureteric shapes sizes were quantified 3D wholemount kidneys. A with live imaging fluorescently labelled UB cells, traction force microscopy, primary cells used determine how basic features niche biomechanics contribute complex point determination process that aims gaining optimal growth density limited space. Results Machine learning-based tip epithelia identified geometrical round-to-elliptical transformation key change facilitating shifts direction enable propitious complexity. Cell analyses demonstrated failure condense conformation. Analysis derived disrupted E-CADHERIN PAXILLIN mediated adhesive forces defective cytoskeletal dynamics detected fluorescent labelling actin cells. Branching-compromised showed wrinkled nuclear alterations MYH9-based microtubule organization, suggest stiff disturbed sensing response biomechanical cues. Conclusions Our results indicate within epithelium towards composed progenitors must dynamically fluctuate allow complexity arborization new formation. The data collectively propose model crowding tandem stretching transforms individual into elliptical elongated shapes. This creates local curvatures drive formation ampulla-to-asymmetric ampulla transition bud.

Язык: Английский

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