Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 13, Pages 5016-5021Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1218025110
Keywords
reaction-diffusion; oscillations; excitable media; self-organization; PTEN
Categories
Funding
- Human Frontier Science Program [RGY 70/2008]
- Precursory Research for Embryonic Science and Technology (PRESTO)
- Japan Science and Technology Agency
- Uehara Memorial Foundation
- Japan Society for the Promotion of Science (JSPS) [23111506, 22680024]
- JST PRESTO
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Grants-in-Aid for Scientific Research [24115503, 22680024] Funding Source: KAKEN
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In both randomly moving Dictyostelium and mammalian cells, phosphatidylinositol (3,4,5)-trisphosphate and F-actin are known to propagate as waves at the membrane and act to push out the protruding edge. To date, however, the relationship between the wave geometry and the patterns of amoeboid shape change remains elusive. Here, by using phase map analysis, we show that morphology dynamics of randomly moving Dictyostelium discoideum cells can be characterized by the number, topology, and position of spatial phase singularities, i.e., points that represent organizing centers of rotating waves. A single isolated singularity near the cellular edge induced a rotational protrusion, whereas a pair of singularities supported a symmetric extension. These singularities appeared by strong phase resetting due to de novo nucleation at the back of preexisting waves. Analysis of a theoretical model indicated excitability of the system that is governed by positive feedback from phosphatidylinositol (3,4,5)-trisphosphate to PI3-kinase activation, and we showed experimentally that this requires F-actin. Furthermore, by incorporating membrane deformation into the model, we demonstrated that geometries of competing waves explain most of the observed semiperiodic changes in amoeboid morphology.
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