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.