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Posted: May 21, 2008
Nanotechnology zippers for membranes
(Nanowerk Spotlight) Nanotechnology researchers have appropriated the name of Janus - the Roman god of gates and doorways, usually depicted with two heads looking in opposite directions - to name a class of amphiphilic (i.e. containing both hydrophobic and hydrophilic portions) nanoparticles composed of two fused hemispheres, each made from a different substance. Their particular structure makes Janus particles an intriguing subject for exploring novel anti-cancer therapies where they, for instance, carry two different and complementary medicines. In a novel use of Janus particles, researchers have now isolated a means of using them to make 're-sealable' pores in lipid bilayer membranes. Described in another way, the localization of the nanoparticles in the pore can be thought of as the placement of a zipper, which allows a specific slit to be opened or closed at will.
"We used computational modeling to show that Janus particles in solution will localize to the edges of a pore in a lipid bilayer membrane" Dr. Anna Balazs tells Nanowerk. "The Janus nanoparticles stabilize the pore location and size so that material can perform in a reliable, repeatable manner; it is this critical feature that the Janus particles contribute to the system. The amphiphilic nature of the Janus particles is crucial for this behavior since portions of the particles must interface with the hydrophobic regions and certain regions must interface with the aqueous solution in the hole."
Balazs, Distinguished Professor of Chemical Engineering and Robert Von der Luft Professor at the University of Pittsburgh, explains that Janus particle-lipid bilayer vesicles would form the ideal vehicles for the delivery of various chemicals, from paints and inks to personal care products and pharmaceuticals.
In their work, the scientists demonstrate that when a lipid bilayer membrane rips under an externally applied tension, the Janus nanoparticles, which have been added to the solution surrounding the membrane, diffuse to the edge of the hole and form a stable pore. Once the applied tension is removed, the hole closes.
Once the particle-lined pore is formed, a small increase in membrane tension readily reopens the pore, allowing transport through the membrane. Besides the application of an external force, the membrane tension can be altered by varying environmental conditions. Thus, the findings provide guidelines for designing nanoparticle-bilayer assemblies for targeted delivery, where the pores open and the cargo is released only when the local conditions surrounding the membrane reach a critical value.
Snapshots of a lipid bilayer membrane in the presence of 27 nanoparticles with α=60°. The green beads mark the hydrophilic head groups in the lipid, while the gray particles indicate the hydrophobic tails. The blue beads mark the hydrophilic portion of the nanoparticles and the red beads indicate the hydrophobic portion. Snapshots A and B show a pore that was formed in a stretched membrane, where nanoparticles attach to the edge of the pore. Snapshots C and D show a nanoparticle-line pore formed when the membrane stretching is released (the blue beads constitute the hydrophilic sites in the Janus nanoparticle, while the red beads are the hydrophobes). Solvent is not shown. (Reprinted with permission from American Chemical Society)
"In particular," says Balazs "the pores would remain closed under one set of conditions (temperature, pH), but would open to release the cargo that was encapsulated in the lipid vesicles when the conditions changed. Thus, you could design responsive materials that deliver the payload only under the appropriate conditions."
Balazs further explains that, without the nanoparticles, the lipids would reassemble to fill in the gap when the tension was released. And with the next application of the tension, the pore could form elsewhere in the membrane, with potentially a different size or shape. The localization of the nanoparticles stabilizes the pore location, size and shape so that material can perform in a reliable, repeatable manner; it is this critical feature that the Janus particles contribute to the system. The amphiphilic nature of the Janus beads is crucial for this behavior since portions of the beads must interface with the hydrophobic regions and certain regions must interface with the aqueous solution in the hole.
She points out that, in addition to facilitating the design and fabrication of responsive materials and useful delivery systems, the nanoparticle-laden assemblies could also be harnessed as sensors. In particular, the pores can be tailored to have a particular size and these synthetic channels could be used to detect and trap molecules of a specific size.
In a previous study, Balazs and her team have examined the interactions between homogeneous nanoparticles (i.e., not Janus particles) and lipid bilayers to establish routes for driving the bilayers to engulf the particles and thereby mimic the biological function of phagocytosis ("Designing synthetic vesicles that engulf nanoscopic particles"). The present study evolved from this earlier work.
To carry out this present study, the researchers used dissipative particle dynamics (DPD) simulations. This technique has proven to be especially useful in studying the mesoscale behavior of bilayer membranes.
"The Janus nanoparticle self-assembly described in our study mimics the behavior of certain peptides and proteins, which form and stabilize channels in biological bilayers" says Balazs. "In effect, we determined optimal conditions for harnessing the nanoparticles to act as 'artificial proteins', which can be used to create gateways and regulate the trafficking of molecules into and out of synthetic membranes and vesicles."
Recent advances in synthetic chemistry have enabled the facile fabrication of Janus particles of various sizes and shapes. The predictions from these simulations therefore could be readily tested. "Now is an ideal time for further investigations into the behavior and potential utility of assemblies formed from Janus nanoparticles and lipid bilayers" says Balazs.