YAP localization mediates mechanical adaptation of human cancer cells during extravasationin vivo

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 16, 2023

Abstract Biophysical profiling of primary tumors has revealed that individual tumor cells fall along a highly heterogeneous continuum mechanical phenotypes. One idea is subset “softer” to facilitate detachment and escape from the site, step required initiate metastasis. However, it also been postulated must be able deform generate sufficient force exit into distant sites. Here, we aimed dissect changes occur during extravasation organ colonization. Using multiplexed methods intravital microscopy optical tweezer based active microrheology, obtained longitudinal images profiles colonization in vivo . We determined were softer, more liquid like upon vasculature but stiffened became solid once new microenvironment. YAP mediated mechanogenotype influenced global dissemination our vitro models reducing heterogeneity could reduce extravasation. Moreover, high throughput analysis phenotypes patient samples this mechanics was part regulated by external hydrodynamic forces cancer experienced within capillary mimetics. Our findings indicate disseminated can keep mutating with landscape mechano-phenotypes, governed YAP-mediated mechanosensing flow.

Language: Английский

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Pioneer in Molecular Biology: Conformational Ensembles in Molecular Recognition, Allostery, and Cell Function

Published: Jan. 1, 2024

Language: Английский

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Engineering FRET biosensor for H3K9 acetylation imaging in single living cells

Med-X, Journal Year: 2024, Volume and Issue: 2(1)

Published: Dec. 11, 2024

Abstract Histone acetylation is an important epigenetic modification that governs gene expression, chromatin changes in stress response, and cell fate transition. FRET biosensors have been developed for various events to enable spatiotemporal tracking of sub-cellular signaling events. Previously reported histone H3 biosensor recognizing two acetyl residues lacked specificity. In this study, using a single bromodomain the BRD4, we genetically encoded H3K9ac biosensor. We systematically investigated different combinations BET family protein as binding domains performed site-saturated mutagenesis optimize biosensor, achieving dynamic change up 30% under TSA treatment. With application optimized revealed basal active architectures invasive tumor cells compared benign cells. Furthermore, found level increased dramatically when cancer passed through microchannels, which models physical constraints mechanical microenvironmental conditions encounter passing narrow spaces within body. This result highlights plasticity response external stresses. summary, our provides versatile tool mechanistic investigation transition mechanotransduction. Graphical

Language: Английский

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Changing Shape of Molecules

Journal of Molecular Biology, Journal Year: 2023, Volume and Issue: 435(11), P. 168092 - 168092

Published: June 1, 2023

Language: Английский

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