Evidence map›Paper›PMID 41201825›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Chemical compensation to mechanical loss in cell mechanosensation.

Qin Ni, Zhuoxu Ge, Anindya Sen, Yufei Wu, Jinyu Fu, Alice Amitrano, Nitish Srivastava, Konstantinos Konstantopoulos, Sean X Sun

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Compartmental pH regulation in cancer and antitumor immunity: therapeutic opportunities and challenges.Apoptosis : an international journal on programmed cell death · 2026
    Review
  2. Cell-nanoplastics association impacts cell proliferation and motility.bioRxiv : the preprint server for biology · 2026
    Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Qin Ni *Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
Zhuoxu Ge *Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
Anindya Sen *Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
Yufei WuInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.ORCID 0000-0002-7724-4359
Jinyu FuDepartment of Physics and Astronomy, Johns Hopkins University, Baltimore, MD 21218.
Alice AmitranoInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
Nitish SrivastavaInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
Konstantinos KonstantopoulosInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.ORCID 0000-0003-2623-1459
Sean X SunInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.ORCID 0000-0002-9077-7088

Funding

The Role of Hydraulic Pressure in the Osmotic Engine Model of Cell MigrationR01GM134542 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI SEAN X SUN · 2019 to 2026
$2.1M
HHS | National Institutes of Health (NIH) R01GM134542
6 · The paper itself

Abstract

Mammalian cells sense and respond to environmental changes using a complex and intelligent system that integrates chemical and mechanical signals. The transduction of mechanical cues into chemical changes modulates cell physiology, allowing a cell to adapt to its microenvironment. Understanding how the chemical and mechanical regulatory modules interact is crucial for elucidating mechanisms of mechanosensation and cellular homeostasis. In this study, we find that cells exhibit nonmonotonic changes in cell volume and intracellular pH when subjected to physical stimuli and varying degrees of actomyosin cytoskeleton disruption. We find that these nonmonotonic responses are mediated by a chemical compensation mechanism, where the attenuation of actomyosin activity stimulates the activity of PI3K/Akt pathway. This, in turn, activates sodium-hydrogen exchanger 1 (NHE1), resulting in elevated intracellular pH and increased cell volume. Furthermore, we identify a competitive interaction between the PI3K/Akt and MAPK/ERK pathways-two major regulators of cell proliferation and motility. This competition modulates the chemical compensation based on the relative activities of these pathways. Our mathematical modeling reveals the network structure that is essential for establishing the nonmonotonic response. Interestingly, this regulatory system is altered in HT1080 fibrosarcoma, highlighting a potential mechanistic divergence in cancer cells in contrast to their normal-like counterpart, such as NIH 3T3 and HFF-1 fibroblasts. Overall, our work reveals a compensatory mechanism between chemical and mechanical signals, providing an infrastructure to elucidate the integrated mechanochemical response to environmental stimuli.

Indexed as

Mechanotransduction, CellularActomyosinAnimalsCell MovementCell ProliferationCell SizeCytoskeletonHumansHydrogen-Ion ConcentrationMAP Kinase Signaling SystemMiceNIH 3T3 CellsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSignal TransductionSodium-Hydrogen Exchanger 1ActomyosinPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSodium-Hydrogen Exchanger 1biophysical modelingcell volumecytoskeletonmechanosensationPI3K signaling

Identifiers

PMID41201825
PMCPMC12625946

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.