Controlling membrane tension by dynamic DNA nanorings

Abstract

Membrane tension, defined as the energy cost to expand the membrane surface area, is a fundamental mechanical property of the lipid bilayer and an important modulator of various cellular processes. Liposomes provide model systems to study protein-mediated membrane dynamics, where membrane tension can be controlled by osmotic pressure and micropipette aspiration. However, it is challenging to individually control membrane tension of nanometer-sized liposomes, such as small unilamellar vesicles (SUVs), that are widely used for modeling subcellular membrane structures and drug delivery. To bridge this technological gap, we present reconfigurable DNA origami rings for dynamically controlling membrane tension of sub-100 nm liposomes. The DNA nanorings template the formation of uniformly sized SUVs and undergo trigger-responsive dilation and contraction, thus applying controlled and reversible mechanical stress to the SUV membranes. Electron microscopy analyses show deformed liposomes with ~2.5% expanded membrane area following ring dilation. The corresponding increase in membrane tension opens a mechanosensitive ion channel MscL with gating tension of ~10 mN/m. Selectively manipulating a mixture of SUV populations enables timed release of their distinct molecular cargos, either concurrently or one at a time. Furthermore, vesicles with expanded membranes are more conducive to SNARE-mediated fusion. The nanomechanical device thus provides a programmable platform for engineering the mechanics of synthetic nano-vesicles and studying membrane tension modulated processes at the molecular level.