This study concerns the self-assembly of virus-like particles (VLPs) composed of an icosahedral virus protein coat encapsulating a functionalized spherical nanoparticle core. The recent development of efficient methods for VLP self-assembly has opened the way to structural studies. Using electron microscopy with image reconstruction, the structures of several VLPs obtained from brome mosaic virus capsid proteins and gold nanoparticles were elucidated. Varying the gold core diameter provides control over the capsid structure. The number of subunits required for a complete capsid increases with the core diameter. The packaging efficiency is a function of the number of capsid protein subunits per gold nanoparticle. VLPs of varying diameters were found to resemble to three classes of viral particles found in cells (T ‫؍‬ 1, 2, and 3). As a consequence of their regularity, VLPs form three-dimensional crystals under the same conditions as the wild-type virus. The crystals represent a form of metallodielectric material that exhibits optical properties influenced by multipolar plasmonic coupling. metamaterials ͉ protein cage ͉ self-assembly ͉ surface plasmon ͉ virus assembly E ngineered virus capsids and protein cage structures have shown increasing promise as therapeutic and diagnostic vectors (1-6), imaging agents (7-10), and as templates and microreactors for advanced nanomaterials synthesis (11)(12)(13)(14)(15)(16)(17). Here, we address the rules for the formation of symmetric protein cages consisting of viral capsid subunits formed over a functionalized inorganic nanoparticle core, called virus-like particles (VLPs).VLPs provide an example of how biomimetic self-organization can combine the natural characteristics of virus capsids with the exquisite physical properties of nanoparticles (18)(19)(20). Interactions between the artificial cargo and the protein carrier affects both the self-assembly and the stability of the resulting structure, yet very little is known about them. Progress toward the basic development and the practical use of VLPs requires an understanding of how relevant parameters contribute to complex formation.Symmetric VLPs may provide a technology for therapeutic or diagnostic agent delivery that is improved over amorphous shell nanoparticles that are already known to be efficient in similar applications (21). The advantage of a regular surface protein motif is that the binding domains are functionally identical by virtue of their equivalent environment. It has been shown in several situations that receptor-mediated targeting can be achieved even when using amorphous coatings (22). However, the principle challenges for nanoparticle delivery currently include: limited life-time in body fluids, nanoparticle transduction across the cellular membrane, avoidance of the exocytotic pathways, and target specificity. To optimize their infectivity, viruses have evolved to overcome these challenges. We still must learn how to apply virus strategies to targeted delivery. A simple question is central to this o...

Efficient encapsulation of functionalized spherical nanoparticles by viral protein cages was found to occur even if the nanoparticle is larger than the inner cavity of the native capsid. This result raises the intriguing possibility of reprogramming the self-assembly of viral structural proteins. The iron oxide nanotemplates used in this work are superparamagnetic, with a blocking temperature of about 250 K, making these virus-like particles interesting for applications such as magnetic resonance imaging and biomagnetic materials. Another novel feature of the virus-like particle assembly described in this work is the use of an anionic lipid micelle coat instead of a molecular layer covalently bound to the inorganic nanotemplate. Differences between the two functionalization strategies are discussed.