Passive transport of Ca2D ions through lipid bilayers imaged by widefield second harmonic microscopy

In biology, release of Ca2+ ions in the cytosol is essential to trigger or control many cell functions. Calcium signaling acutely depends on lipid membrane permeability to Ca2+. For proper understanding of membrane permeability to Ca2+, both membrane hydration and the structure of the hydrophobic core must be taken into account. Here, we vary the hy-drophobic core of bilayer membranes and observe different types of behavior in high-throughput wide-field second harmonic imaging. Ca2+ translocation is observed through mono-unsaturated (DOPC:DOPA) membranes, reduced upon the addition of cholesterol, and completely inhibited for branched (DPhPC:DPhPA) and poly-unsaturated (SLPC:SLPA) lipid membranes. We propose, using molecular dynamics simulations, that ion transport occurs through ion-induced transient pores, which re-quires nonequilibrium membrane restructuring. This results in different rates at different locations and suggests that the hydro-phobic structure of lipids plays a much more sophisticated regulating role than previously thought.

Automated summary

In biology, the release of Ca2+ ions in the cytosol is crucial for cell functions, and calcium signaling depends on membrane permeability to Ca2+. This study investigates the impact of varying the hydrophobic core of bilayer membranes on Ca2+ translocation. The results suggest that ion transport occurs through transient pores, which require membrane restructuring, and the hydrophobic structure of lipids plays a more sophisticated regulating role than previously thought.