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Local Membrane Curvature Pins and Guides Excitable Membrane Waves in Chemotactic and Macropinocytic Cells - Biomedical Insights From an Innovative Simple Model

PIP3 dynamics observed in membranes are responsible for the protruding edge
formation in cancer and amoeboid cells. The mechanisms that maintain those PIP3
domains in three-dimensional space remain elusive, due to limitations in observation
and analysis techniques. Recently, a strong relation between the cell geometry, the
spatial confinement of the membrane, and the excitable signal transduction system has
been revealed by Hörning and Shibata (2019) using a novel 3D spatiotemporal analysis
methodology that enables the study of membrane signaling on the entire membrane
(Hörning and Shibata, 2019). Here, using 3D spatial fluctuation and phase map analysis
on actin polymerization inhibited Dictyostelium cells, we reveal a spatial asymmetry of
PIP3 signaling on the membrane that is mediated by the contact perimeter of the plasma
membrane—the spatial boundary around the cell-substrate adhered area on the plasma
membrane. We show that the contact perimeter guides PIP3 waves and acts as a
pinning site of PIP3 phase singularities, that is, the center point of spiral waves. The
contact perimeter serves as a diffusion influencing boundary that is regulated by a cell
size- and shape-dependent curvature. Our findings suggest an underlying mechanism
that explains how local curvature can favor actin polymerization when PIP3 domains get
pinned at the curved protrusive membrane edges in amoeboid cells.

Identiferoai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84508
Date03 April 2023
CreatorsHörning, Marcel, Bullmann, Torsten, Shibata, Tatsuo
PublisherFrontiers Research Foundation
Source SetsHochschulschriftenserver (HSSS) der SLUB Dresden
LanguageEnglish
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text
Rightsinfo:eu-repo/semantics/openAccess
Relation2296-634X, 670943

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