Photocontrol of the translocation of molecules, peptides, and quantum dots through cell and lipid membranes doped with azobenzene copolymers.

Permeabilization of lipid membranes is a major challenge for the development of biocides and for improving the delivery of DNA, anticancer agents, and small proteins within the cell cytosol. Effective membrane permeabilization can be achieved by chemical techniques that often involve an intramembrane assembly of permeabilizing agents such as peptides, amphiphilic molecules, or polymers. Alternative physical techniques are electroporation or microinjection. A present challenge for chemical approaches lies in targeting cells while maintaining cell viability. The development of permeabilizers for the remote control of membrane properties is accordingly in high demand to compete with microinjection, because the former avoids mechanical damage and addresses large cell subsets. The strategy consists of using so-called “smart” systems, that is, tailoring stimuli-responsive molecules to affect lipid membranes. The variation of the pH value has been the major focus for the design of smart bilayers doped with polymers or peptides with the goal of delivering substances of interest in the late endosomes or targeting acidic tumors. However, light-responsive systems would offer a more versatile and external trigger. To photocontrol self-assembly and/or interaction with lipid bilayers several authors had recourse to amphiphilic azobenzene derivatives. The best achievements in this field show a modulation of the rate of transmembrane release of small molecules from liposomes, the membranes of which contain either a pore-forming peptide, gramicidin, conjugated to azobenzene or an azobenzene-containing lipid. However, except for highly specific photogating by engineered membrane proteins, no artificial system (likely less specific than protein gates) enabled phototriggered permeabilization on living cells. So far, in regard to large molecules (e.g. peptides), their pH-controlled passage was essentially achieved using polymer carriers. Herein, we show that azobenzene-modified polymers (AMPs; Scheme 1) can impart plasma membranes of living cells and vesicles with this desirable photoresponse.