Progress Toward Cell-Directed Assembly of Nanostructures

This research contributes to the development of bio/nano interfaces and new classes of biotic/abiotic materials.

During 2007, progress was made on several fronts in a research program oriented toward developing capabilities for biocompatible and biomimetic self-assembly of nanostructures that could perform desired functions as interfaces between biological and nanotechnological systems ("bio/nano" interfaces). These capabilities are expected to contribute, in turn, to development of new classes of biotic/abiotic materials and to understanding of responses of cells to diseases, injuries, stresses, and therapies. The approach followed in this research has been one of striving to understand and exploit celldirected assembly (CDA).

The objectives for 2007 and the efforts to attain those objectives are summarized below.

• Objective: Understand cell-directed assembly and use it to direct the formation of new bio/nano interfaces and unique cellular behaviors.

This Fluorescence Image, obtained by confocal scanning microscopy, show slices of yeast cells immobilized in silica matrices that were patterned partly by use of dihexanoylphosphatidylcholine (a lipid) and palmitoyl oleoyl phosphatidylcholine liposomes.
The pursuit of this objective included an investigation of the inclusion of multiple amphipathic components to control and tailor interfacial structures and functions. This investigation was prompted in part by the observation that plasma membranes in cells incorporate multiple amphipathic components, including phospho- and glycolipids, cholesterol, and integral and peripheral proteins. The amphipathic components studied in this investigation included water-soluble lipids and water-soluble liposomes (see figure).

The pursuit of the abovementioned objective included a demonstration of creation of new interfaces through modification of cells to incorporate non- native functional proteins. In this demonstration, by use of a novel technique, a CDA process was used to incorporate, into surface layers of yeast cells, bacteriorhodopsin from Halobacterium salinarum.

Objective: Extend CDA to immobilize cells of various types.

This effort involved encapsulation of cells from several new cell lines, (including mammalian cells) in nanostructured silica and host matrices. The nanostructures and bio/nano interfaces were studied by use of grazing-incidence x-ray scattering, epifluoresecence microscopy, and confocal scanning laser microscopy.

It is expected that nanostructured matrices could be made to serve, not only as hosts for immobilized cells, but also as reservoirs for nutrients and growth factors for controlling metabolic activity. Accordingly, this effort included an investigation of new media in which to conduct CDA so as to incorporate essential nutrients and growth factors into the silica host matrices.

Objective: Pattern cells to create functional multi-cellular materials wherein nanostructure is used to influence cell-to-cell communication and thereby influence cellular behavior.

A biocompatible photolithographic patterning process developed specifically for this purpose includes an ultraviolet/ ozone-exposure subprocess that creates the desired pattern in the form of areas that are more or less hydrophilic, followed by a selective-wetting subprocess in which cells suspended in an aqueous medium become preferentially deposited in more-hydrophilic areas. By use of an appropriate pattern on an ultraviolet mask, this process could be used to create porous regions, between localized cells, that could be used to introduce nutrient media, growth factors, toxins, or other molecules of interest.

What may be a new pathway for communication among cells was demonstrated in experiments in which silica nanostructures were found to affect the gradients of concentration of quorum-sensing molecules of cells immobilized in the nanostructures. These experiments are regarded as a first step toward establishing a conceptual platform for studying intercellular communications.

This work was done by C. Jeffrey Brinker, Eric Carnes, Carlee Ashley, Juewen Liu, DeAnna Lopez, Cynthia Douthit, Shelly Karlin, Jennifer Pelowitz, and Landon White of the University of New Mexico for the Air Force Research Laboratory.



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Progress Toward Cell-Directed Assembly of Nanostructures

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Defense Tech Briefs Magazine

This article first appeared in the February, 2008 issue of Defense Tech Briefs Magazine (Vol. 2 No. 1).

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Overview

The document presents a final report on a research project titled "Biocompatible and Biomimetic Self-Assembly of Functional Nanostructures," led by C. Jeffrey Brinker at the University of New Mexico. The project, funded by the Air Force Office of Scientific Research, aimed to explore innovative methods for creating functional nanostructures that are both biocompatible and biomimetic, which means they mimic biological processes and structures.

The research focuses on cell-directed assembly (CDA), a technique that utilizes living cells to guide the formation of nanostructures. This approach allows for the integration of biological components with synthetic materials, leading to enhanced functionalities and applications in various fields, including biomedicine and materials science. The report highlights the significance of using amphipathic components and non-native functional proteins to achieve desired properties in the assembled structures.

Key findings from the research include the successful encapsulation of different cell types within nano-structured hosts, which can potentially lead to advancements in drug delivery systems and tissue engineering. The document also discusses the characterization of transport behavior in composite mesoporous silica thin films, which are crucial for understanding how these nanostructures interact with biological systems.

The report emphasizes the impact of Brinker’s work, noting high citation rates and recognition through awards and media coverage. His seminal paper on evaporation-induced self-assembly was recognized as one of the top 20 papers of the decade by ISI, reflecting the significance of his contributions to the field. Additionally, Brinker has been appointed as a Regent's Professor and has an increasing citation H-index, indicating the growing influence of his research.

The document also outlines various invited talks and presentations at international conferences, showcasing the global interest in Brinker’s work. Overall, the report encapsulates a significant advancement in the field of nanotechnology, particularly in developing biocompatible materials that can interact effectively with biological systems, paving the way for future innovations in healthcare and materials engineering.