Two-Dimensional Interfacial Exchange Diffusion Has the Potential to Augment Spatiotemporal Precision of Ca²⁺ Signaling

Nano-junctions between the endoplasmic reticulum and cytoplasmic surfaces of the plasma membrane and other organelles shape the spatiotemporal features of biological Ca²⁺ signals. Herein, we propose that 2D Ca²⁺ exchange diffusion on the negatively charged phospholipid surface lining nano-junctions participates in guiding Ca²⁺ from its source (channel or carrier) to its target (transport protein or enzyme). Evidence provided by in vitro Ca²⁺ flux experiments using an artificial phospholipid membrane is presented in support of the above proposed concept, and results from stochastic simulations of Ca²⁺ trajectories within nano-junctions are discussed in order to substantiate its possible requirements. Finally, we analyze recent literature on Ca²⁺ lipid interactions, which suggests that 2D interfacial Ca²⁺ diffusion may represent an important mechanism of signal transduction in biological systems characterized by high phospholipid surface to aqueous volume ratios.