The development of hybrid biomaterials using the virus-like particle (VLP) from bacteriophage P22

Abstract

A broad range of bio-composite materials have been developed through inspiration from biology. In particular, natural systems that confine, co-localize and protect their contents has inspired the design and synthesis of the P22 virus-like particle (VLP) to effect a suite of biomaterials. These materials were realized by taking advantage of the native protein architecture of P22 as an initiation point and platform for material synthesis. Introducing a reactive cysteine on the P22 coat protein provided an initiation point for polymer synthesis. Atom transfer radical polymerization (ATRP) was initiated creating a polymer framework on the interior of the P22 VLP. Using this polymerization technique (ATRP) a photocatalytic crosslinker was successfully incorporated for reduction of methyl viologen. Next, a manganese porphyrin imaging agent was loaded creating a T 1-enhanced MRI contrast agent, as an alternative to the highly toxic Gadolinium currently used. Inspired by photosynthetic machinery, the P22-xAEMA system was labeled with a co-catalyst system, creating a co-localized photocatalytic nanoparticle capable of photochemically producing NADH/hydrogen. The production was controlled by labeling density of catalysts resulting in a tunable biomaterial. The design of a complex bio-hybrid material was developed by combining both synthetic and genetic approaches. Coupling the enzyme Alcohol Dehydrogenase D from Pyrococcus furiosis with a small molecule catalyst led to a coupled catalytic system between a synthetic catalyst and biologically derived enzyme. The P22 VLP system was studied by atomic force microscopy (AFM) and cryoelectron microscopy (cryo-EM) unraveling its biophysical properties and providing insights for further material design. 2D-crystal arrays were formed from a variety of P22-protein biomaterials, for the development of functional P22 arrays. Lastly, the P22 VLP was monitored by charge detection mass spectrometry, giving insight into the stability of the scaffolding protein. These studies show the versatility of this system for both material synthesis and fundamental biochemical understandings. Overall, the work here continues to progress and push the boundaries of protein cage nanoparticles as platforms for material synthesis. The development of hybrid biomaterials from VLPs serve to improve our basic understandings of the natural systems they are derived from and provide additional design principles for improved complex biohybrid materials.