Local Membrane Curvature Pins and Guides Excitable Membrane Waves in Chemotactic and Macropinocytic Cells - Biomedical Insights From an Innovative Simple Model
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Media type:
E-Article
Title:
Local Membrane Curvature Pins and Guides Excitable Membrane Waves in Chemotactic and Macropinocytic Cells - Biomedical Insights From an Innovative Simple Model
Description:
PIP3 dynamics observed in membranes are responsible for the protruding edgeformation in cancer and amoeboid cells. The mechanisms that maintain those PIP3domains in three-dimensional space remain elusive, due to limitations in observationand analysis techniques. Recently, a strong relation between the cell geometry, thespatial confinement of the membrane, and the excitable signal transduction system hasbeen revealed by Hörning and Shibata (2019) using a novel 3D spatiotemporal analysismethodology that enables the study of membrane signaling on the entire membrane(Hörning and Shibata, 2019). Here, using 3D spatial fluctuation and phase map analysison actin polymerization inhibited Dictyostelium cells, we reveal a spatial asymmetry ofPIP3 signaling on the membrane that is mediated by the contact perimeter of the plasmamembrane—the spatial boundary around the cell-substrate adhered area on the plasmamembrane. We show that the contact perimeter guides PIP3 waves and acts as apinning site of PIP3 phase singularities, that is, the center point of spiral waves. Thecontact perimeter serves as a diffusion influencing boundary that is regulated by a cellsize- and shape-dependent curvature. Our findings suggest an underlying mechanismthat explains how local curvature can favor actin polymerization when PIP3 domains getpinned at the curved protrusive membrane edges in amoeboid cells.