Abstract
Progress in our understanding of mechanotransduction events requires noninvasive methods for the manipulation of forces at molecular scale in physiological environments. Inspired by cellular mechanisms for force application (i.e. 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. 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 entangled polymer chains, which will in turn effectively “pull” on engaged cell membrane receptors (e.g., integrins, T cell receptors) within the illuminated area. 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. 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.
Highlights
Progress in our understanding of mechanotransduction events requires noninvasive methods for the manipulation of forces at molecular scale in physiological environments
The stator part is linked to two triethylene glycol (TEG) chains connected to the membrane receptor of interest via a complementary ligand (i.e., RGD or anti-CD3)
The exact binding configuration at the membrane receptor cluster is unknown, we expect that multivalency of the motor surface stabilizes the connection between integrins and the short spacer in view of a short-lived receptor-ligand bond
Summary
To rule out that UV irradiation on its own could induce the observed FA area changes, similar experiments were performed in MEF cells on control surfaces conjugated with non-rotary motors (locked by a single episulfide moiety in place of the rotating double bond, Supplementary Scheme 1) In this case, no difference in total FA area between UV-illuminated and nonilluminated regions was observed (Fig. 1e). No response was observed when the Jurkat cells were seeded on control motor (no rotation) surfaces exposed to UV light (Fig. 2b, c) These results indicate that the observed response was not associated to UV illumination per se, but it was a consequence of the applied pulling force on the TCR by the rotary motor linked to anti-CD3. The flexibility of the design, not coupled to materials or special techniques, will allow extension of this technique to natural biointerfaces and in vivo contexts
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