Molecular machines measure the nanomechanics of biological membranes

Mechanical properties such as elastic resistance to distortion define many materials and can routinely be measured with an indenting tip as simple as one’s finger. We have miniaturized the indentation principle by 8 orders of magnitude to analyze lipid bilayer nanomechanics, which are of relevance in biology and disease progression. Our nanoscale indenting tip is designed with DNA nanotechnology to be an integral part of a molecular machine which autonomously binds to membranes, actively indents localized membrane patches, measures the membranes’ elastic response to indentation, and converts the indentation degree into an optical readout signal. Compared to serially operated macro-to-microscale indentation probes, our miniaturization strategy enables deploying millions of the indenting machines for parallel analysis of membrane elasticity. The nanoscale molecular machines are also taken up by biological cells to reveal softer inner membrane compartments compared to stiffer cytoplasmic membranes, using indentation depths of solely up to 1 nm. We envision the DNA-based nanotools to contribute to the analysis of membrane mechanics of cells as well as soft polymeric interphases.