Shape control of deformable charge-patterned nanoparticles.

Deformable nanoparticles (NPs) offer unprecedented opportunities as dynamic building blocks that can spontaneously reconfigure during assembly in response to environmental cues. Designing reconfigurable materials based on deformable NPs hinges on an understanding of the shapes that can be engineered in these NPs. We solve for the low-energy shapes of charge-patterned deformable NPs by using molecular dynamics-based simulated annealing to minimize a coarse-grained model Hamiltonian characterized with NP elastic and electrostatic energies subject to a volume constraint.

Multilayered Ordered Protein Arrays Self-Assembled from a Mixed Population of Virus-like Particles.

Biology shows many examples of spatially controlled assembly of cells and biomacromolecules into hierarchically organized structures, to which many of the complex biological functions are attributed. While such biological structures have inspired the design of synthetic materials, it is still a great challenge to control the spatial arrangement of individual building blocks when assembling multiple types of components into bulk materials. Here, we report self-assembly of multilayered, ordered protein arrays from mixed populations of virus-like particles (VLPs).

In Silico Development of Combinatorial Therapeutic Approaches Targeting Key Signaling Pathways in Metabolic Syndrome.

Purpose: Dysregulations of key signaling pathways in metabolic syndrome are multifactorial, eventually leading to cardiovascular events. Hyperglycemia in conjunction with dyslipidemia induces insulin resistance and provokes release of proinflammatory cytokines resulting in chronic inflammation, accelerated lipid peroxidation with further development of atherosclerotic alterations and diabetes. We have proposed a novel combinatorial approach using FDA approved compounds targeting IL-17a and DPP4 to ameliorate a significant portion of the clustered clinical risks in patients with metabolic syndrome.

Percolation Theory Reveals Biophysical Properties of Virus-like Particles.

The viral protein containers that encapsulate a virus' genetic material are repurposed as virus-like particles in a host of nanotechnology applications, including cargo delivery, storage, catalysis, and vaccination. These viral architectures have evolved to sit on the knife's edge between stability, to provide adequate protection for their genetic cargoes, and instability, to enable their efficient and timely release in the host cell environment upon environmental cues. By introducing a percolation theory for viral capsids, we demonstrate that the geometric characteristics of a viral capsid in terms of its subunit layout and intersubunit interaction network are key for its disassembly behavior.

Designing Surface Charge Patterns for Shape Control of Deformable Nanoparticles.

Designing reconfigurable materials based on deformable nanoparticles (NPs) hinges on an understanding of the energetically favored shapes these NPs can adopt. Using simulations, we show that hollow, deformable, patchy NPs tailored with surface charge patterns such as Janus patches, stripes, and polyhedrally distributed patches differently adapt their shape in response to changes in patterns and ionic strength, transforming into capsules, hemispheres, variably dimpled bowls, and polyhedra. The links between anisotropy in NP surface charge, shape, and the elastic energy density are discussed.

Computational studies of shape control of charged deformable nanocontainers.

Biological matter is often compartmentalized by soft membranes that dynamically change their shape in response to chemical and mechanical cues. Deformable soft-matter-based nanoscale membranes or nanocontainers that mimic this behavior can be used as drug-delivery carriers that can adapt to evolving physiological conditions, or as dynamic building blocks for the design of novel hierarchical materials via assembly engineering. Here, we connect the intrinsic features of charged deformable nanocontainers such as their size, charge, surface tension, and elasticity with their equilibrium shapes for a wide range of solution conditions using molecular dynamics simulations.

Linker-Mediated Assembly of Virus-Like Particles into Ordered Arrays via Electrostatic Control.

Nanoscale virus-like particles (VLPs), which are self-assembled from protein subunits, offer the possibility of generating hierarchically assembled functional materials such as biomimetic catalytic systems and optical metamaterials. We explore the capacity to control and tune a higher-order assembly of VLPs into ordered array materials over a wide range of ionic conditions using a combination of experimental and computational methods. The integrated methodology demonstrates that P22 VLP variants, genetically engineered to exhibit different surface charges, self-assemble into ordered arrays in the presence of PAMAM dendrimers acting as oppositely charged, macromolecular linkers.

Competition between Normative and Drug-Induced Virus Self-Assembly Observed with Single-Particle Methods.

Disruption of virus capsid assembly has compelling antiviral potential that has been applied to hepatitis B virus (HBV). HBV core protein assembly can be modulated by heteroaryldihydropyrimidines (HAPs), and such molecules are collectively termed core protein allosteric modulators (CpAMs). Although the antiviral effects of CpAMs are acknowledged, the mechanism of action remains an open question.

Molecular jenga: the percolation phase transition (collapse) in virus capsids.

Virus capsids are polymeric protein shells that protect the viral cargo. About half of known virus families have icosahedral capsids that self-assemble from tens to thousands of subunits. Capsid disassembly is critical to the lifecycles of many viruses yet is poorly understood.

A molecular breadboard: Removal and replacement of subunits in a hepatitis B virus capsid.

Hepatitis B virus (HBV) core protein is a model system for studying assembly and disassembly of icosahedral structures. Controlling disassembly will allow re-engineering the 120 subunit HBV capsid, making it a molecular breadboard. We examined removal of subunits from partially crosslinked capsids to form stable incomplete particles.