ArticleProceedings of the National Academy of Sciences of the United States of America2010
Cells navigate with a local-excitation, global-inhibition-biased excitable network.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 157 papers.
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Who cites it
157 citing papers in PubMed, 284 citations in OpenAlex.
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- From microscope to model: rotating signaling dynamics and cluster size in Dictyostelium discoideum aggregates.BMC molecular and cell biology · 2026Article
- SHIP1 partitions between cortical oscillations and membrane puncta to regulate neutrophil chemotaxis.bioRxiv : the preprint server for biology · 2026Article
- Local Ras/actin signaling orients individual pseudopods in shallow gradients.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Distinct impact of PI(4)P flux on PI(4,5)PProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Emergent eukaryotic directional sensing via receptor degradation and diffusion.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- PIP5K-Ras bistability triggers plasma membrane symmetry breaking to define cellular polarity and regulate migration.bioRxiv : the preprint server for biology · 2025Article
- Spatial distribution of cytoskeleton-mediated feedback controls cell polarization: A computational study.PLoS computational biology · 2025Article
- Signaling and actin waves at a glance.Journal of cell science · 2025Review
- Front-biased activation of the Ras-Rab5-Rac1 loop coordinates collective cell migration.Journal of cell science · 2025Article
- Nanoscale Curvature Regulates YAP/TAZ Nuclear Localization Through Nuclear Deformation and Rupture.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Two endogenousProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Protrusion force and cell-cell adhesion-induced polarity alignment govern collective migration modes.Biophysical journal · 2025Article
- Spatial distribution of cytoskeleton-mediated feedback controls cell polarization: a computational study.bioRxiv : the preprint server for biology · 2025Article
- Excitable Ras dynamics-based screens reveal RasGEFX is required for macropinocytosis and random cell migration.Nature communications · 2025Article
- Genetically encodable biosensors for Ras activity.RSC chemical biology · 2024Review
- Three-component contour dynamics model to simulate and analyze amoeboid cell motility in two dimensions.PloS one · 2024Article
- Spontaneous signal generation by an excitable system for cell migration.Frontiers in cell and developmental biology · 2024Review
- Particle-based simulations reveal two positive feedback loops allow relocation and stabilization of the polarity site during yeast mating.PLoS computational biology · 2023Article
- Pathological and Therapeutic Significance of Tumor-Derived Extracellular Vesicles in Cancer Cell Migration and Metastasis.Cancers · 2023Review
97 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Cells have an internal compass that enables them to move along shallow chemical gradients. As amoeboid cells migrate, signaling events such as Ras and PI3K activation occur spontaneously on pseudopodia. Uniform stimuli trigger a symmetric response, whereupon cells stop and round up; then localized patches of activity appear as cells spread. Finally cells adapt and resume random migration. In contrast, chemotactic gradients continuously direct signaling events to the front of the cell. Local-excitation, global-inhibition (LEGI) and reaction-diffusion models have captured some of these features of chemotaxing cells, but no system has explained the complex response kinetics, sensitivity to shallow gradients, or the role of recently observed propagating waves within the actin cytoskeleton. We report here that Ras and PI3K activation move in phase with the cytoskeleton events and, drawing on all of these observations, propose the LEGI-biased excitable network hypothesis. We formulate a model that simulates most of the behaviors of chemotactic cells: In the absence of stimulation, there are spontaneous spots of activity. Stimulus increments trigger an initial burst of patches followed by localized secondary events. After a few minutes, the system adapts, again displaying random activity. In gradients, the activity patches are directed continuously and selectively toward the chemoattractant, providing an extraordinary degree of amplification. Importantly, by perturbing model parameters, we generate distinct behaviors consistent with known classes of mutants. Our study brings together heretofore diverse observations on spontaneous cytoskeletal activity, signaling responses to temporal stimuli, and spatial gradient sensing into a unified scheme.
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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.