ArticleProceedings of the National Academy of Sciences of the United States of America2012
Synthetic spatially graded Rac activation drives cell polarization and movement.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 72 citations in OpenAlex.
- Investigating local negative feedback of Rac activity by mathematical models and cell-motility simulations.iScience · 2026Article
- Methods for Controlling Small GTPase Activity.Chembiochem : a European journal of chemical biology · 2025Review
- Modelling the effect of cell motility on mixing and invasion in epithelial monolayers.Journal of biological physics · 2024Article
- Synthetic control of actin polymerization and symmetry breaking in active protocells.Science advances · 2024Article
- Optogenetic Signaling Activation in Zebrafish Embryos.Journal of visualized experiments : JoVE · 2023Article
- Micro-engineering and nano-engineering approaches to investigate tumour ecosystems.Nature reviews. Cancer · 2023Review
- Generation of Dynamic Concentration Profile Using A Microfluidic Device Integrating Pneumatic Microvalves.Biosensors · 2022Article
- Article
- Two Complementary Signaling Pathways Depict Eukaryotic Chemotaxis: A Mechanochemical Coupling Model.Frontiers in cell and developmental biology · 2021Article
- Bridging from single to collective cell migration: A review of models and links to experiments.PLoS computational biology · 2020Review
- Simple Rho GTPase Dynamics Generate a Complex Regulatory Landscape Associated with Cell Shape.Biophysical journal · 2020Article
- Dynamics of Mechanosensitive Nascent Adhesion Formation.Biophysical journal · 2019Article
- Subdiffusive Dynamics Lead to Depleted Particle Densities near Cellular Borders.Biophysical journal · 2019Article
- Computational modeling of single-cell mechanics and cytoskeletal mechanobiology.Wiley interdisciplinary reviews. Systems biology and medicine · 2018Review
- Mechanisms of Cell Polarization.Current opinion in systems biology · 2017Article
- A mathematical model coupling polarity signaling to cell adhesion explains diverse cell migration patterns.PLoS computational biology · 2017Article
- Cancer cell motility: lessons from migration in confined spaces.Nature reviews. Cancer · 2017Review
- Many roads to symmetry breaking: molecular mechanisms and theoretical models of yeast cell polarity.Molecular biology of the cell · 2017Review
- A mathematical model of GTPase pattern formation during single-cell wound repair.Interface focus · 2016Review
- Following Optogenetic Dimerizers and Quantitative Prospects.Biophysical journal · 2016Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Migrating cells possess intracellular gradients of active Rho GTPases, which serve as central hubs in transducing signals from extracellular receptors to cytoskeletal and adhesive machinery. However, it is unknown whether shallow exogenously induced intracellular gradients of Rho GTPases are sufficient to drive cell polarity and motility. Here, we use microfluidic control to generate gradients of a small molecule and thereby directly induce linear gradients of active, endogenous Rac without activation of chemotactic receptors. Gradients as low as 15% were sufficient not only to trigger cell migration up the chemical gradient but to induce both cell polarization and repolarization. Cellular response times were inversely proportional to the steepness of Rac inducer gradient in agreement with a mathematical model, suggesting a function for chemoattractant gradient amplification upstream of Rac. Increases in activated Rac levels beyond a well-defined threshold augmented polarization and decreased sensitivity to the imposed gradient. The threshold was governed by initial cell polarity and PI3K activity, supporting a role for both in defining responsiveness to Rac activation. Our results reveal that Rac can serve as a starting point in defining cell polarity. Furthermore, our methodology may serve as a template to investigate processes regulated by intracellular signaling gradients.
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Registered trials
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.