Biological membranes are semipermeable barriers protecting cells and cellular compartments from surrounding environments. Peptides with the right properties can spontaneously cross this barrier, which is only a few nanometers thick. Such peptides could be used as drug carriers or therapeutics themselves, but what are these “right” properties of peptides? And are there any other factors that can come into play and enable peptides to cross the membrane?

In our study, we investigated whether membrane proteins could be one such factor. Biological membranes consist of lipid bilayers and thus are often mimicked by lipid-only systems. However, membrane proteins can make up as much as 50% of the mass of the membrane. Furthermore, one group of membrane proteins, called scramblases, facilitates the spontaneous bidirectional translocation of lipids between membrane leaflets. We hypothesized that other amphiphilic molecules could exploit scramblases to facilitate their translocation.

The cover art of the June 1 issue of Biophysical Journal is an artistic rendering of putative translocation of an α-helical peptide along a scramblase, which has a partially hydrophilic membrane-exposed domain. The light trail indicates the peptide trajectory from the surrounding environment into the cell interior. The system was assembled using tools available in the GROMACS software and rendered with Blender.

As we highlight in our study and on the cover, membrane proteins can indeed facilitate translocation of amphiphilic molecules into cells and should be considered in the design of potential drug carriers. Moreover, proteins with similar properties to scramblases could be utilized in synergistic mixtures to enhance the translocation of other molecules. More about our research can be found at http://vacha.ceitec.cz/.

- Ladislav Bartoš, Ivo Kabelka, Robert Vácha