Henri Franquelim: Remodeling of lipid membranes: Membrane bending by DNA origami scaffolds

Biological membranes are dynamic cellular barriers that suffer deformation and bending. Despite huge effort in identifying the physical-chemical fundaments of such phenomena, particular mechanisms and elements are still poorly understood. In order to fill this gap, minimal biomimetic curvature-inducing DNA origami structures, that emulate the characteristics of BAR domain proteins, were engineered [1]. BAR domains are important curved peripheral membrane proteins capable of inducing and stabilizing curvature on cellular membranes. Here, I developed cholesteryl-modified DNA origami scaffolding units of different degrees of curvature and stacking features, that can interact with lipid model membranes and, above all, reproduce the sculpting activity of BAR proteins. Distinctive membrane deformations, such as tubulation, could be triggered at increased scaffold membrane densities, and the shape of those deformations correlated with the intrinsic curvature of the DNA origami nanostructures. Taken together, this novel approach reveals a minimal set of modules and preconditions required for shape-dependent membrane curvature generation (such as degree of curvature, membrane affinity and surface density), opening up exciting perspectives for using DNA origami nanotechnology in the fields of Molecular to Cellular-scale Biophysics.

[1] Franquelim HG, Khmelinskaia A, Sobczak JP, Dietz H, Schwille P (2018) Membrane sculpting by curved DNA origami scaffolds. Nat Commun, 9(1): 811.