February 2022
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34 Reads
Biophysical Journal
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Publications (3)
October 2020
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275 Reads
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312 Citations
Science
The physical microenvironment regulates cell behavior during tissue development and homeostasis. How single cells decode information about their geometrical shape under mechanical stress and physical space constraints within tissues remains largely unknown. Here, using a zebrafish model, we show that the nucleus, the biggest cellular organelle, functions as an elastic deformation gauge that enables cells to measure cell shape deformations. Inner nuclear membrane unfolding upon nucleus stretching provides physical information on cellular shape changes and adaptively activates a calcium-dependent mechanotransduction pathway, controlling actomyosin contractility and migration plasticity. Our data support that the nucleus establishes a functional module for cellular proprioception that enables cells to sense shape variations for adapting cellular behavior to their microenvironment.
December 2019
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415 Reads
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5 Citations
The physical microenvironment regulates cell behavior during tissue development and homeostasis. How single cells decode information about their geometrical shape under mechanical stress and physical space constraints within their local environment remains largely unknown. Here we show that the nucleus, the biggest cellular organelle, functions as a non-dissipative cellular shape deformation gauge that enables cells to continuously measure shape variations on the time scale of seconds. Inner nuclear membrane unfolding together with the relative spatial intracellular positioning of the nucleus provides physical information on the amplitude and type of cellular shape deformation. This adaptively activates a calcium-dependent mechano-transduction pathway, controlling the level of actomyosin contractility and migration plasticity. Our data support that the nucleus establishes a functional module for cellular proprioception that enables cells to sense shape variations for adapting cellular behaviour to their microenvironment. One Sentence Summary The nucleus functions as an active deformation sensor that enables cells to adapt their behavior to the tissue microenvironment.
Citations (2)
... In practice, the ability to extract the "correct" features has been a bottleneck 16 . Traits commonly used by pathologists (e.g., cell type) are non-trivial to engineer, while histological presentation of novel discriminative features in cancers are often unintuitive due to tissue complexity and tumor variability, making them hard to formulate [17][18][19][20][21][22][23][24][25][26][27][28] . In contrast, deep learning (DL) algorithms, which bypass the task of feature engineering, have excelled on a wide range 9, 29-33 of histopathology-based predictions, matching human performance on traditional classification tasks and enabled predictions of mutation status, gene expression, molecular subtypes and treatment response [34][35][36] . ...
- Citing Article
October 2020
Science
... More globally, recent work by our lab and others (Lomakin et al., 2019;Venturini et al., 2019) showed that contractility is activated upon confinement by a mechanoresponse pathway mediated by the release of calcium and the activation of the enzyme cPLA2 (Enyedi et al., 2016). These works proposed that the contractility activation happens under 5µm compression due to nuclear stretching and that the stretch depended on the cell cycle stage or the state of the nuclear lamina. ...
- Citing Preprint
- File available
December 2019