Fig. 2

All-atom MD simulation of lipid scrambling induced by a DNA nanostructure. a, b Microscopic configuration of the simulated system at the beginning (a) and the end (b) of the free equilibration simulation. Top: cut-away view showing the DNA nanostructure (blue and yellow) embedded in a DPhPE lipid membrane (gray) via cholesterol tags (red). Lipid head groups located in the upper and lower leaflet of the bilayer at 0.2 µs are highlighted using purple and green spheres, respectively. Bottom: Top view of the simulated system; the electrolyte solution is not shown for clarity. Black ellipses highlight DPhPE head groups that resided at 0.2 µs in the lower leaflet of the bilayer. For lower leaflet lipid arrangements see Supplementary Fig. 2. c Sequence of microscopic conformations illustrating spontaneous inter-leaflet transfer of one lipid molecule (#51, highlighted by the bold depiction) during the 2.2 µs MD simulation. For clarity, all other lipid molecules are shown using a different representation; the electrolyte solution is not shown. Arrows illustrate the trajectory of the lipid during the simulation. d Radial distance relative to the center of mass of the nanostructure R (left axis) and the Z coordinate of the phosphorus atoms (right axis) of a lipid molecule (#51, see b and c) undergoing a complete transfer from the lower to the upper leaflet of the bilayer. Dashed red lines indicate Z-coordinate thresholds for the upper and lower bilayer leaflet. Data shown were sampled at 0.24 ns and averaged in 9.6 ns blocks. Supplementary Figure 3 and Supplementary Movies 2-4 show additional examples of inter-leaflet lipid transfer. e Cumulative number of inter-leaflet transfer events vs. simulation time. A linear fit (black dashed line) yields the average transfer rate; the error indicates the estimated standard deviation of the nonlinear least squares fit