RT Journal Article SR Electronic T1 Optoregulated force application to cellular receptors using molecular motors JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.03.31.015198 DO 10.1101/2020.03.31.015198 A1 Yijun Zheng A1 Mitchell K.L. Han A1 Renping Zhao A1 Johanna Blass A1 Jingnan Zhang A1 Dennis W. Zhou A1 Jean-Rémy Colard-Itté A1 Damien Dattler A1 Markus Hoth A1 Andrés J. García A1 Bin Qu A1 Roland Bennewitz A1 Nicolas Giuseppone A1 Aránzazu del Campo YR 2020 UL http://biorxiv.org/content/early/2020/04/01/2020.03.31.015198.abstract AB Mechanotransduction events in physiological environments are difficult to investigate, in part due to the lack of experimental tools to apply forces to mechanosensitive receptors remotely. Inspired by cellular mechanisms for force application (i.e. motor proteins pulling on cytoskeletal fibers), here we present a unique molecular machine that can apply forces at cell-matrix and cell-cell junctions using light as an energy source. The key actuator is a light-driven rotatory molecular motor linked to polymer chains, which is intercalated between a membrane receptor and an engineered biointerface. The light-driven actuation of the molecular motor is converted in mechanical twisting of the polymer chains, which will in turn effectively “pulls” on engaged cell membrane receptors (integrins, cadherins…) within the illuminated area. Applied forces have the adequate magnitude and occur at time scales within the relevant ranges for mechanotransduction at cell-friendly exposure conditions, as demonstrated in forcedependent focal adhesion maturation and T cell activation experiments. Our results reveal the potential of nanomotors for the manipulation of living cells at the molecular scale and demonstrate, for the first time, a functionality which at the moment cannot be achieved by any other means.