Molecular machines open cell membranes

• Published in: Nature (London) 2017-08, Vol.548 (7669), p.567-572
• Main Authors: García-López, Víctor, Chen, Fang, Nilewski, Lizanne G., Duret, Guillaume, Aliyan, Amir, Kolomeisky, Anatoly B., Robinson, Jacob T., Wang, Gufeng, Pal, Robert, Tour, James M.
• Format: Article
• Language: English
• Subjects: 14; 140/131; 631/61; 631/80/2373; 639/301/54/152; 639/925/350; 639/925/927/339; Activation; Actuation; Animals; Apoptosis; Biomedical materials; Cell death; Cell Membrane - chemistry; Cell Membrane - metabolism; Cell membranes; Cell surface; Cell Survival; Chemical speciation; Conformation; Diffusion; Dyes; Experiments; External stimuli; Gangrene; HEK293 Cells; Humanities and Social Sciences; Humans; I.R. radiation; In vitro methods and tests; Infrared Rays; Introduced species; letter; Light; Lipid bilayers; Lipid Bilayers - chemistry; Lipid Bilayers - metabolism; Lipids; Magnetic fields; Membranes; Mice; Microscopy; Molecular machines; Molecular Motor Proteins - metabolism; Molecular Motor Proteins - radiation effects; Molecular motors; Movement - radiation effects; multidisciplinary; Nanotechnology; Near infrared radiation; Necrosis; NIH 3T3 Cells; Patch-Clamp Techniques; Photons; Physiological aspects; Rotation; Science; Species; Species diffusion; Ultrasound; Ultraviolet radiation; Ultraviolet Rays
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature23657

Rotary molecular machines, activated by ultraviolet light, are able to perturb and drill into cell membranes in a controllable manner, and more efficiently than those exhibiting flip-flopping or random motion. Molecular machine 'drills' through cell membranes Victor García-López et al . report that ultraviolet-light-activated rotary molecular machines are able to perturb and drill into cell membranes in vitro . Molecules without the drilling action, which either flip-flopped in a washing-machine-like motion or demonstrated random rotation, were inefficient at traversing the cell membrane compared to those with unidirectional motion. Membrane perturbation was rapidly followed by membrane blebbing, and necrosis. Changing the structure of the motors sterically slowed the transport across the membrane, while the addition of peptides to the molecular motors allowed targeting of the molecules to specific cells. This research offers new opportunities for molecular motors in bioengineering applications. Beyond the more common chemical delivery strategies, several physical techniques are used to open the lipid bilayers of cellular membranes 1 . These include using electric 2 and magnetic 3 fields, temperature 4 , ultrasound 5 or light 6 to introduce compounds into cells, to release molecular species from cells or to selectively induce programmed cell death (apoptosis) or uncontrolled cell death (necrosis). More recently, molecular motors and switches that can change their conformation in a controlled manner in response to external stimuli have been used to produce mechanical actions on tissue for biomedical applications 7 , 8 , 9 . Here we show that molecular machines can drill through cellular bilayers using their molecular-scale actuation, specifically nanomechanical action. Upon physical adsorption of the molecular motors onto lipid bilayers and subsequent activation of the motors using ultraviolet light, holes are drilled in the cell membranes. We designed molecular motors and complementary experimental protocols that use nanomechanical action to induce the diffusion of chemical species out of synthetic vesicles, to enhance the diffusion of traceable molecular machines into and within live cells, to induce necrosis and to introduce chemical species into live cells. We also show that, by using molecular machines that bear short peptide addends, nanomechanical action can selectively target specific cell-surface recognition sites. Beyond the in vitro applications