Spatial modeling of the membrane-cytosolic interface in protein kinase signal transduction

The spatial architecture of signaling pathways and the inter-action with cell size and morphology are complex but little understood. With the advances of single cell imaging and single cell biology it becomes crucial to understand intracel-lular processes in time and space. Activation of cell surface receptors often triggers a signaling cascade including the activation of membrane-attached and cytosolic signaling components, which eventually transmit the signal to the cell nucleus. Signaling proteins can form steep gradients in the cytosol, which cause strong cell size dependence. We show that the kinetics at the membrane-cytosolic interface and the ratio of cell membrane area to the enclosed cytosolic volume change the behavior of signaling cascades significantly. We present a mathematical analysis of signal transduction in time and space by providing analytical solutions for different spatial arrangements of linear signaling cascades. These investigations are complemented by numerical simulations of non-linear cascades and asymmetric cell shapes.