Three-dimensional cell geometry controls excitable membrane signaling in Dictyotelium cells

Phosphatidylinositol (3,4,5)-trisphosphate (PtdInsP3) is known to propagate as waves on the plasma membrane and is related to the membrane protrusive activities in Dictyostelium and mammalian cells. While there have been a few attempts to study the three-dimensional dynamics of these processes, most studies have focused on the dynamics extracted from single focal planes. However, the relation between the dynamics and three-dimensional cell shape remains elusive, due to the lack of signaling information about the unobserved part of the membrane. Here we show that PtdInsP3 wave dynamics are directly regulated by the three-dimensional geometry - size and shape - of the plasma membrane. By introducing an analysis method that extracts the three-dimensional spatiotemporal activities on the entire cell membrane, we show that PtdInsP3 waves self-regulate their dynamics within the confined membrane area. This leads to changes in speed, orientation and pattern evolution, following the underlying excitability of the signal transduction system. Our findings emphasize the role of the plasma membrane topology in reaction-diffusion driven biological systems and indicate its importance in other mammalian systems.