"Furadeiras" moleculares abrem membranas celulares: mero acaso, fortuita necessidade ou design inteligente?

quinta-feira, agosto 31, 2017

Molecular machines open cell membranes

Víctor García-López, Fang Chen, Lizanne G. Nilewski, Guillaume Duret, Amir Aliyan, Anatoly B. Kolomeisky, Jacob T. Robinson, Gufeng Wang, Robert Pal & James M. Tour

Affiliations Contributions Corresponding authors

Nature 548, 567–572 (31 August 2017) doi:10.1038/nature23657   

Received 07 September 2016 Accepted 05 July 2017 

Published online 30 August 2017


Beyond the more common chemical delivery strategies, several physical techniques are used to open the lipid bilayers of cellular membranes1. These include using electric2 and magnetic3 fields, temperature4, ultrasound5 or light6 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 applications789. 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 demonstrated here, we expect that molecular machines could also be used in vivo, especially as their design progresses to allow two-photon, near-infrared and radio-frequency activation10.