Evidence map›Paper›PMID 36202973›Full record

ArticleNature cell biology2022

Spatiotemporal dynamics of membrane surface charge regulates cell polarity and migration.

Tatsat Banerjee, Debojyoti Biswas, Dhiman Sankar Pal, Yuchuan Miao, Pablo A Iglesias, Peter N Devreotes

Open access · greenAbstract read
In one paragraph

Article in Nature cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
9.6field-weighted citation impact, top 1% of its field
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

57 citing papers in PubMed, 85 citations in OpenAlex.

  1. Article
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  8. Distinct impact of PI(4)P flux on PI(4,5)PProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  9. Article
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  11. Mechanobiological Dynamics-Inspired Mechanomodulatory Biomaterials.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  12. Article
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  20. Signaling and actin waves at a glance.Journal of cell science · 2025
    Review
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

6 authors at 1 institution in 1 country.

Tatsat BanerjeeDepartment of Cell Biology and Center for Cell Dynamics, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0002-3490-3959
Debojyoti Biswas *Department of Electrical and Computer Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA.
Dhiman Sankar Pal *Department of Cell Biology and Center for Cell Dynamics, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0002-8442-3507
Yuchuan MiaoDepartment of Cell Biology and Center for Cell Dynamics, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0003-0600-6609
Pablo A IglesiasDepartment of Cell Biology and Center for Cell Dynamics, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0002-0840-155X
Peter N DevreotesDepartment of Cell Biology and Center for Cell Dynamics, School of Medicine, Johns Hopkins University, Baltimore, MD, USA. pnd@jhmi.edu.ORCID 0000-0002-3260-1455
Johns Hopkins University · US

Funding

Excitable Networks in Directed Cell MigrationR35GM118177 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI Peter N Devreotes · 2016 to 2026
$12.1M
Zeiss LSM780 Confocal Microscope for a Core FacilityS10OD016374 · OD · JOHNS HOPKINS UNIVERSITY · PI KUO, SCOT CHARLES · 2013 to 2013
$584k
NIGMS NIH HHS R35 GM118177NIH HHS S10 OD016374
6 · The paper itself

Abstract

During cell migration and polarization, numerous signal transduction and cytoskeletal components self-organize to generate localized protrusions. Although biochemical and genetic analyses have delineated many specific interactions, how the activation and localization of so many different molecules are spatiotemporally orchestrated at the subcellular level has remained unclear. Here we show that the regulation of negative surface charge on the inner leaflet of the plasma membrane plays an integrative role in the molecular interactions. Surface charge, or zeta potential, is transiently lowered at new protrusions and within cortical waves of Ras/PI3K/TORC2/F-actin network activation. Rapid alterations of inner leaflet anionic phospholipids-such as PI(4,5)P2, PI(3,4)P2, phosphatidylserine and phosphatidic acid-collectively contribute to the surface charge changes. Abruptly reducing the surface charge by recruiting positively charged optogenetic actuators was sufficient to trigger the entire biochemical network, initiate de novo protrusions and abrogate pre-existing polarity. These effects were blocked by genetic or pharmacological inhibition of key signalling components such as AKT and PI3K/TORC2. Conversely, increasing the negative surface charge deactivated the network and locally suppressed chemoattractant-induced protrusions or subverted EGF-induced ERK activation. Computational simulations involving excitable biochemical networks demonstrated that slight changes in feedback loops, induced by recruitment of the charged actuators, could lead to outsized effects on system activation. We propose that key signalling network components act on, and are in turn acted upon, by surface charge, closing feedback loops, which bring about the global-scale molecular self-organization required for spontaneous protrusion formation, cell migration and polarity establishment.

Indexed as

ActinsCell PolarityCell MembraneCell MovementChemotactic FactorsEpidermal Growth FactorMechanistic Target of Rapamycin Complex 2Phosphatidylinositol 3-KinasesPhosphatidylserinesProto-Oncogene Proteins c-aktActinsChemotactic FactorsEpidermal Growth FactorMechanistic Target of Rapamycin Complex 2Phosphatidylinositol 3-KinasesPhosphatidylserinesProto-Oncogene Proteins c-akt

Identifiers

PMID36202973
PMCPMC10029748
OpenAlexW4302362773

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.