Research

Neural Biomimetics

Although significant advances have been made in the field of tissue engineering, the idea of engineering tissues in vitro that will result in functional organs continues to be a challenging task. However, these concepts provide us with tools that can aid in investigation of several in vivo phenomena (e.g., tumor cell migration). Traditionally, cells have been cultured and studied in tissue culture plates (2D environments). However, it is now well known that cell response is drastically altered when exposed to 3D microenvironments. Unfortunately, most of the 3D studies for investigating neural cancers utilize substrates that are physiologically not relevant. With an ultimate goal of better understanding tumor cell migration in vitro, we are developing neural biomimetic materials that mimic mechanics, chemistry and topography of the in vivo environment. These biomimetic materials also have import to the field of neuroprosthetics, where they can be used as electrode coatings to enhance biocompatibility. Ultimately, we would like to develop a physiologically relevant in vitro brain model to study various complex phenomena (e.g., neural development).

Cellular Nanoprobes for the Nervous System

Charles Sodini

SK-N-SH neuroblastoma cells labeled with CdS quantum dots (yellow). Quantum dots are targeted to cell surface receptors (integrins) using peptides.

Nanoparticles have already made a substantial impact in the field of biological imaging because of their small size, bright fluorescent signals, narrow bandwidths, and long-lived fluorescence. However, nanoparticles display many unique properties that result from their size, which is on the order of 5-10 nm. Certain nanomaterials can be moved using magnetic field, other materials produce heat when the absorb light, and yet other materials produce an electric field upon light absorption. Several of these properties could be used to directly manipulate and investigate cellular features, which display similar size scales to the nanoparticles themselves. In previous work, we investigated the later phenomenon, attempting to create particles that could convert light to electrical energy (similar to a photodiode) used to stimulate of nerve cells placed near the particles. Most present applications of active nanoprobes investigate similar phenomenon taking place on the cell surface. Introducing particles to the cell interior is a significant challenge. We are creating cellular nanoprobes designed to enter a cell and interact with its individual components. These particles are multifunctional containing both an imaging and interactive component (e.g., magnetism) which allows for direct manipulation of cellular features. Particles also contain targeting molecules providing a mechanism for their precise placement within the cell. These particles represent a significant advance in cellular engineering, the ability to manipulate the subcellular environment, and will provide biologists with new tools for biological investigation.

Nanopatterns for Directed Neuronal Growth

The interaction of a cell with its physical environment is a critical determinant of cell adhesion, migration, survival, and differentiation. However, this is one of the most understudied areas of biology. Some work has been performed to understand how cells respond to environments of various stiffness and also microscale features. Yet, cell-environment interactions are primarily mediated by integrins, 10 nm diameter proteins embedded in the cell membrane that experience a conformational change when binding components of the outside environment. It is logical that nanometer scale patterns of integrin binding domains could have a huge impact on cell function, but little work has been performed in this area because of the difficulty in creating reproducible, stable nanometer scale patterns that extend to cellular dimensions (~ 10 mm). We are developing new techniques for creating ordered nanometer scale patterns that can be used to investigate cell-surface interactions.

Collaborators

Ohio State University

Jeffrey Chalmers, Chemical Engineering

R. Sooryakumar, Physics

Barbara Wyslouzil, Chemical Engineering

L. James Lee, Chemical Engineering

Sanjay Rajagopalan, Cardiovascular Medicine

John Lannutti, Materials Science and Engineering

Rebecca Dupaix, Mechanical Engineering

Heather Powell, Materials Science and Engineering

External

George Bachand (Sandia National Labs)

Atom Sarkar (University of Arkansas)

Peter Kner (University of Georgia)

Beth Brainerd (Brown University)

Ge Yang (Carnegie Mellon University)

Carol Lynn Alpert (Museum of Science, Boston).

Funding Sources

National Science Foundation

National Institutes of Health

H.C. “Slip” Slider Professorship

Institute for Materials Research (IMR), Ohio State University

Women in Philanthropy, Ohio State University