In this work, we envisioned using molecular motor-polymer conjugates to apply external mechanical forces to individual membrane receptors of a living cell, and to trigger mechanotransduction processes therefrom.
In this configuration, the original rotary motion is transformed into a contraction of the chain ensemble, with the potential to pull on individual nanoscale objects 4, 6, 7, 8, 9. When rotary motors are coupled to fixed elements through a number of polymer chains, the rotational actuation of the motor forces conformational twisting and thus an increasing entanglement of the polymer chains. Among synthetic molecular devices, light-driven rotary motors based on over-crowded alkene molecules are able to autonomously cycle unidirectional 360° rotations around their central double bond by using light and temperature as combined sources of energy 5. The objective of the present study focuses on the application of external forces to cells using an artificial, purely synthetic molecular motor 4. Being able to apply mechanical signals to cells at the molecular scale in cell culture models or tissues is of great value in the understanding of these diseases.Ĭells generate forces at the molecular scale through directional polymerization of actin filaments and by the action of myosin as ATP-driven molecular motor 3.
Perturbations along the chain of mechanical sensing and biochemical responses lead to various pathological disorders such as loss of hearing, cardiovascular dysfunction, muscular dystrophy, and cancer. This mechano-sensitive feedback modulates cellular functions as diverse as proliferation, differentiation, migration, and apoptosis, and is crucial for tissue formation, homeostasis, repair, and pathogenesis. In turn, biochemical signals regulate cellular and extracellular mechanical properties. Our results reveal the potential of nanomotors for the manipulation of living cells at the molecular scale and demonstrate a functionality which at the moment cannot be achieved by other technologies for force application.Įxternal mechanical stimuli are sensed and translated by cells into biochemical signals in a process called mechanotransduction 1, 2. Applied forces have physiologically-relevant magnitude and occur at time scales within the relevant ranges for mechanotransduction at cell-friendly exposure conditions, as demonstrated in force-dependent focal adhesion maturation and T cell activation experiments. The light-driven actuation of the molecular motor is converted in mechanical twisting of the entangled polymer chains, which will in turn effectively “pull” on engaged cell membrane receptors (e.g., integrins, T cell receptors) within the illuminated area. 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. motor proteins pulling on cytoskeletal fibers), we present a unique molecular machine that can apply forces at cell-matrix and cell-cell junctions using light as an energy source.
Inspired by cellular mechanisms for force application (i.e.
Progress in our understanding of mechanotransduction events requires noninvasive methods for the manipulation of forces at molecular scale in physiological environments.
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