A mechano-osmotic feedback couples cell volume to the rate of cell deformation
- Institut Curie, CNRS, UMR 144, France
- European Molecular Biology Laboratory, Germany
- Laboratoire Interdisciplinaire de Physique, France
- Sorbonne Université, INSERM, France
- Institut Curie, CNRS UMR168, France
Abstract
Mechanics has been a central focus of physical biology in the past decade. In comparison, how cells manage their size is less understood. Here we show that a parameter central to both the physics and the physiology of the cell, its volume, depends on a mechano-osmotic coupling. We found that cells change their volume depending on the rate at which they change shape, when they spontaneously spread are externally deformed. Cells undergo slow deformation at constant volume, while fast deformation leads to volume loss. We propose a mechano-sensitive pump and leak model to explain this phenomenon. Our model and experiments suggest that volume modulation depends on the state of the actin cortex and the coupling of ion fluxes to membrane tension. This mechano-osmotic coupling defines a membrane tension homeostasis module constantly at work in cells, causing volume fluctuations associated with fast cell shape changes, with potential consequences on cellular physiology.
Data availability
All data generated or analysed during this study are included in themanuscript and supporting file; all the raw analysed data shown in thefigure panels in the article are available in the accompanying SourceData files
Article and author information
Author details
Stéphane Vassilopoulos
Jean-François Joanny
Funding
Agence Nationale de la Recherche (ANR-19-CE13-0030)
- Matthieu Piel
Agence Nationale de la Recherche (ANR-10-EQPX-34)
- Matthieu Piel
Agence Nationale de la Recherche (ANR-10-IDEX-0001-02 PSL)
- Matthieu Piel
Agence Nationale de la Recherche (ANR-10-LABX-31)
- Matthieu Piel
Fondation pour la Recherche Médicale (FDT201805005592)
- Larisa Venkova
Human Frontier Science Program (LT000305/2018-L)
- Nishit Srivastava
Agence Nationale de la Recherche (ANR‐17‐CE13‐0020‐02)
- Amit Singh Vishen
European Union's Horizon 2020 research and innovation programme (Marie Sklodowska-Curie grant agreement no. 641639)
- Larisa Venkova
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Venkova et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 6,999
- views
-
- 1,163
- downloads
-
- 59
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
A mechano-osmotic feedback couples cell volume to the rate of cell deformation
eLife 11:e72381.
https://doi.org/10.7554/eLife.72381
Further reading
-
- Cell Biology
- Developmental Biology
Fibroblast growth factor (FGF) signaling elicits multiple downstream pathways, most notably the Ras/MAPK cascade facilitated by the adaptor protein Grb2. However, the mechanism by which Grb2 is recruited to the FGF signaling complex remains unresolved. Here, we showed that genetic ablation of FGF signaling prevented murine lens induction by disrupting transcriptional regulation and actin cytoskeletal arrangements, which could be reproduced by deleting the juxtamembrane region of the FGF receptor and rescued by Kras activation. Conversely, mutations affecting the Frs2-binding site on the FGF receptor or the deletion of Frs2 and Shp2 primarily impact later stages of lens vesicle development involving lens fiber cell differentiation. Our study further revealed that the loss of Grb2 abolished MAPK signaling, resulting in a profound arrest of lens development. However, removing Grb2’s putative Shp2 dephosphorylation site (Y209) neither produced a detectable phenotype nor impaired MAPK signaling during lens development. Furthermore, the catalytically inactive Shp2 mutation (C459S) only modestly impaired FGF signaling, whereas replacing Shp2’s C-terminal phosphorylation sites (Y542/Y580) previously implicated in Grb2 binding only caused placental defects, perinatal lethality, and reduced lacrimal gland branching without impacting lens development, suggesting that Shp2 only partially mediates Grb2 recruitment. In contrast, we observed that FGF signaling is required for the phosphorylation of the Grb2-binding sites on Shc1 and the deletion of Shc1 exacerbates the lens vesicle defect caused by Frs2 and Shp2 deletion. These findings establish Shc1 as a critical collaborator with Frs2 and Shp2 in targeting Grb2 during FGF signaling.
-
- Cell Biology
Diacylglycerols (DAGs) are used for metabolic purposes and are tightly regulated secondary lipid messengers in eukaryotes. DAG subspecies with different fatty-acyl chains are proposed to be involved in the activation of distinct PKC isoforms, resulting in diverse physiological outcomes. However, the molecular players and the regulatory origin for fine-tuning the PKC pathway are unknown. Here, we show that Dip2, a conserved DAG regulator across Fungi and Animalia, has emerged as a modulator of PKC signalling in yeast. Dip2 maintains the level of a specific DAG subpopulation, required for the activation of PKC-mediated cell wall integrity pathway. Interestingly, the canonical DAG-metabolism pathways, being promiscuous, are decoupled from PKC signalling. We demonstrate that these DAG subspecies are sourced from a phosphatidylinositol pool generated by the acyl-chain remodelling pathway. Furthermore, we provide insights into the intimate coevolutionary relationship between the regulator (Dip2) and the effector (PKC) of DAG-based signalling. Hence, our study underscores the establishment of Dip2-PKC axis about 1.2 billion years ago in Opisthokonta, which marks the rooting of the first specific DAG-based signalling module of eukaryotes.
