Nuclease-Resistant L-DNA Tension Probes Enable Long-Term Force Mapping of Single Cells and Cell Consortia.

DNA-based tension probes with precisely programmableforce response provide important insights into cellularmechanosensing. However, their degradability in cell culture limitstheir use for long-term imaging, for instance, when cells migrate,divide, and differentiate. This is a critical limitation for providinginsights into mechanobiology for these longer-term processes. Here,we present DNA-based tension probes that are entirely designedbased on the stereoisomer of biological D-DNA, i.e., L-DNA. Wedemonstrate that L-DNA tension probes are essentially indestructibleby nucleases and provide days-long imaging without significant lossin image quality. We also show their superiority already for shortimaging times commonly used for classical D-DNA tension probes.We showcase the potential of these resilient probes to image minutemovements, and for generating long term force maps of single cellsand of collectively migrating cell populations.