K. Swaminathan Iyer

Prion-like domains in RNA binding proteins are essential for building subnuclear paraspeckles

Paraspeckles are mammalian subnuclear bodies built on a long noncoding RNA and are enriched in RNA binding proteins with prion-like domains; two of these proteins, RBM14 and FUS, use these domains to hold paraspeckles together.

Multimodal analysis of PEI-mediated endocytosis of nanoparticles in neural cells.

Polymer nanoparticles are widely used as a highly generalizable tool to entrap a range of different drugs for controlled or site-specific release. However, despite numerous studies examining the kinetics of controlled release, the biological behavior of such nanoparticles remains poorly understood, particularly with respect to endocytosis and intracellular trafficking. We synthesized polyethylenimine-decorated polymer nanospheres (ca. 100-250 nm) of the type commonly used for drug release and used correlated electron microscopy, fluorescence spectroscopy and microscopy, and relaxometry to track endocytosis in neural cells. These capabilities provide insight into how polyethylenimine mediates the entry of nanoparticles into neural cells and show that polymer nanosphere uptake involves three distinct steps, namely, plasma membrane attachment, fluid-phase as well as clathrin- and caveolin-independent endocytosis, and progressive accumulation in membrane-bound intracellular vesicles. These findings provide detailed insight into how the intracellular delivery of nanoparticles is mediated by polyethylenimine, which is presently the most commonly used nonviral gene transfer agent. This fundamental knowledge may also assist in the preparation of next-generation nonviral vectors.

Encapsulation and controlled release of nutraceuticals using mesoporous silica capsules

The utility of mesoporous silica particles to encapsulate nutraceuticals and thereby serve as a molecular tracker, a drug carrier and a controlled drug release system is investigated.

Microfluidic size selective growth of palladium nano-particles on carbon nano-onions

Size selective growth of palladium nano-particles 2-7 nm in diameter on the surface of carbon nano-onions (CNOs) (derived from catalytic cracking of methane) in water involves pretreating the CNOs with p-phosphonic acid calix[8]arene then H(2)PdCl(4) followed by dynamic thin film processing under hydrogen in a vortex fluidic device.

Green light-emitting LaPO4:Ce3+:Tb3+ koosh nanoballs assembled by p-sulfonato-calix[6]arene coated superparamagnetic Fe3O4

Superparamagnetic fluorescent nanocomposites based on doped lanthanide phosphate and magnetite nanoparticles are accessible through a facile one-pot method. The bifunctional nanocomposites adopt a koosh ball structure with both fluorescent and superparamagnetic properties for individual components maintained in the final nanostructure.

The structure of human SFPQ reveals a coiled-coil mediated polymer essential for functional aggregation in gene regulation

SFPQ, (a.k.a. PSF), is a human tumor suppressor protein that regulates many important functions in the cell nucleus including coordination of long non-coding RNA molecules into nuclear bodies. Here we describe the first crystal structures of Splicing Factor Proline and Glutamine Rich (SFPQ), revealing structural similarity to the related PSPC1/NONO heterodimer and a strikingly extended structure (over 265 Å long) formed by an unusual anti-parallel coiled-coil that results in an infinite linear polymer of SFPQ dimers within the crystals. Small-angle X-ray scattering and transmission electron microscopy experiments show that polymerization is reversible in solution and can be templated by DNA. We demonstrate that the ability to polymerize is essential for the cellular functions of SFPQ: disruptive mutation of the coiled-coil interaction motif results in SFPQ mislocalization, reduced formation of nuclear bodies, abrogated molecular interactions and deficient transcriptional regulation. The coiled-coil interaction motif thus provides a molecular explanation for the functional aggregation of SFPQ that directs its role in regulating many aspects of cellular nucleic acid metabolism.

In vivo Imaging and Biodistribution of Multimodal Polymeric Nanoparticles Delivered to the Optic Nerve

The use of nanoparticles for targeted delivery of therapeutic agents to sites of injury or disease in the central nervous system (CNS) holds great promise. However, the biodistribution of nanoparticles following in vivo administration is often unknown, and concerns have been raised regarding potential toxicity. Using poly(glycidyl methacrylate) (PGMA) nanoparticles coated with polyethylenimine (PEI) and containing superparamagnetic iron oxide nanoparticles as a magnetic resonance imaging (MRI) contrast agent and rhodamine B as a fluorophore, whole animal MRI and fluorescence analyses are used to demonstrate that these nanoparticles (NP) remain close to the site of injection into a partial injury of the optic nerve, a CNS white matter tract. In addition, some of these NP enter axons and are transported to parent neuronal somata. NP also remain in the eye following intravitreal injection, a non-injury model. Considerable infiltration of activated microglia/macrophages occurs in both models. Using magnetic concentration and fluorescence visualization of tissue homogenates, no dissemination of the NP into peripheral tissues is observed. Histopathological analysis reveals no toxicity in organs other than at the injection sites. Multifunctional nanoparticles may be a useful mechanism to deliver therapeutic agents to the injury site and somata of injured CNS neurons and thus may be of therapeutic value following brain or spinal cord trauma.

Encapsulation and Sustained Release of Curcumin using Superparamagnetic Silica Reservoirs

For controlled release and targeted delivery of curcumin in an aqueous medium a method of encapsulating curcumin and magnetic nanoparticles inside porous silica matrix has been developed. Curcumin and superparamagnetic nanoparticles are loaded inside porous silica in a single process. The graphic shows the TEM image of microtomed sample of Fe(3)O(4) particles surrounded by a silica matrix.

Non-covalently modified graphene supported ultrafine nanoparticles of palladium for hydrogen gas sensing

A facile aqueous based method of decorating p-phosphonic acid calix[8]arene functionalized graphene with well-dispersed ultrafine palladium nanoparticles (∼2 nm) has been developed. The electrocatalytic Pd-NP–graphene nano-composite has been incorporated into a functional hydrogen sensing device using a simple drop casting technique on interdigitated electrodes.

Designer self-assembling hydrogel scaffolds can impact skin cell proliferation and migration

There is a need to develop economical, efficient and widely available therapeutic approaches to enhance the rate of skin wound healing. The optimal outcome of wound healing is restoration to the pre-wound quality of health. In this study we investigate the cellular response to biological stimuli using functionalized nanofibers from the self-assembling peptide, RADA16. We demonstrate that adding different functional motifs to the RADA16 base peptide can influence the rate of proliferation and migration of keratinocytes and dermal fibroblasts. Relative to unmodified RADA16; the Collagen I motif significantly promotes cell migration, and reduces proliferation.