Of Polymers and Phages
August 30, 2007 Leave a comment
After the my recent rantings about publishers and their antics, it is highest time for a polymer post. So here is a lovely piece of work: Graff et al., PNAS, 99(8), 5064 (2002) (doi: 10.1073/pnas.062654499, freely accessible via PubmedCentral).
There is a great deal of research interest in nanocontainers at the moment, specifically those produced via the self-assembly of block copolymers. In this particular example, a poly(2-methyl-2-oxazoline)-block-poly(dimethylsiloxane)-block-poly(2-methyl-2-oxazoline) (PMOXA-PDMS-PMOXA) triblock copolymer (Mn(PMOXA) = 1800 gmol-1, Mn(PDMS) = 5400 gmol-1, PDI = 1.7) is used for the generation of micelles with a diameter of approximately 250 nm in an aqueous phase. Subsequently, the LamB receptor (a porin, which normally forms trimeric channels in the walls of gram-negative bacteria and is used for the transport of maltose and and maltodextrins) was incorporated into the walls of micelles through simple diffusion. Both this paper as well as others have shown that incorporation of proteins into synthetic polymer membranes leaves the proteins functionally intact, although synthetic membranes normally tend to be thicker and more densely packed than natural lipid bilayers.
As it happens, the porin not only acts as a channel, but is also a binding site for the lambda-phage. So when the latter is let loose on the micelles, the authors could observe binding of the phage tail to the protein receptor. Here’s a schematic:
(Reproduced with permission, Copyright PNAS 2002)
and here’s some micrographs:
(Reproduced with permission, Copyright PNAS 2002)
The top micrograph shows a phage bound to a single polymer vesicle, whereas the bottom one shows binding to a vesicle aggregate.
Using a fluorescent dye, the authors could show that, analogous to the process in natural, the phage injects its DNA into the polymer vesicle, where it is protected from the action of hydrolytic enzymes such as DNAse.
I don’t know about you, but I find this type of interface work beautiful and extremely elegant from a purely scientific point of view. The potential usefulness of DNA loaded vesicles in gene therapy applications is obvious and given the wide variety of co-polymer chemistry that we can choose from nowadays, it is even conceivable that one might find a system that has a specific target.
But even if we don’t – it is simply beautiful work.
P.S.: Thank you PNAS for making blogging about this so easy.