Seed Research

Seed #1

Synthetic Development of Novel Organic Electron Transport Materials

Karl A. Scheidt, chemistry

This seed project synthesizes and evaluates materials for potential use in molecular electronics. This work also uses synthesis to address how molecular structure can control electron transport and function. Focus is directed towards compounds that contain conjugated electron donating and electron withdrawing substituents in their molecular architecture. Appropriate installation of thiol or olefin linkers on these synthetically sophisticated electronic scaffolds allows for appendage of the molecules to gold or silicon surfaces. In collaboration, electronic properties of t hese molecules will be studied using a custom - built low temperature ultra high vacuum scanning tunneling microscope. Vibration information under current flow will be measured using surface enhanced Raman spectroscopy.

Structure relationship in electron transport - Starting from simple building blocks, a triaryl mercaptan with opposing electron donating and electron withdrawing functionality can be synthesized and appended to gold surfaces.

Seed #2

Nanocomposite Elastomers for Vascular Tissue Engineering

Guillermo A. Ameer, biomedical engineering

Coronary artery and peripheral vascular disease are the largest causes of mortality in the United States [1]. To treat the consequences of this disease, clinicians rely on donor veins, arteries, or synthetic vascular grafts. Unfortunately, synthetic vascular grafts have had limited success as they occlude and fail within 5 years when used to replace small-diameter blood vessels [2]. This problem has motivated researchers and clinicians to explore tissue engineering approaches to replace blood vessels. However, one of the major challenges has been the development of biomaterials that would recreate mechanical and biochemical characteristics that would promote long-term graft survival [3]. Specifically, the scaffold used for cell growth should be biodegradable, strong, and elastic, as it has been shown that cyclic mechanical strain during tissue development can improve histological organization and enhance extracellular matrix synthesis [4]. Toward these goals, we have developed a new family of biodegradable and elastomeric copolymers based on citric acid and aliphatic diols. These copolymers, referred to as poly(diol citrates), have been shown to be biocompatible with cells, tissues, and blood. To achieve the range of burst pressures and compliance values that that are required for use in the body, we propose to engineer elastomeric poly(diol citrate) nanocomposites that include a poly(l-lactide) nanofiber network [5]. These elastomers will be initially used to optimize the biochemical and mechanical culture conditions for in vitro tissue engineering of a small diameter blood vessel. The specific aims of this research are to:

AIM #1: Synthesize elastomeric poly(diol citrate) nanocomposite biphasic scaffolds that have a high burst pressures (tensile strength of 0.80 MPa, similar to early bypass grafts) and degradation rates (total degradation time of 10-12 weeks). Specifically, we will synthesize poly(diol citrate) nanocomposites where the nanophase consists of poly(lactide-co-glycolide) (PLGA) nanoparticles or poly(L-lactic acid) (PLLA) nanofiber meshes. The chemical, mechanical, and degradation properties will be characterized.

SEM Images (A) 10% PLLA nanofiber network with large micropores and (B) 10% PLLA-PDC nanocomposite.

AIM #2: Investigate the effect of long-term in vitro culture (12 weeks) on burst pressure, compliance, and suturability of the biphasic scaffold. Assess the effect of cyclic radial strain on the formation of a small-diameter vessel in vitro. Specifically, we will seed tubular bi-phasic scaffolds with vascular cells and culture the cell/scaffold construct under 2% (similar to low compliance vessels such as ePTFE) and 12% (similar to human arteries) pulsatile radial strain. The quality of the resulting tissue will be assessed via histology, biochemical assays, and mechanical tests and correlated with the amount of cyclic radial strain.

1. 2001 Heart and stroke statistical update. 2001, American Heart Association: Dallas, TX.
2. Haruguchi, H. and S. Teraoka, Intimal hyperplasia and hemodynamic factors in arterial bypass and arteriovenous grafts: a review. Journal of Artificial Organs, 2003. 6(4): p. 227-335.
3. Thompson, W., Reflection of the pathogenesis of abdominal aortic aneurysms. Cardiovascular Surgery, 2002. 10: p. 389-394.
4. Niklason, L.E., et al., Functional arteries grown in vitro. Science, 1999. 284(5413): p. 489-93.
5. Yang, J., A. Webb, and G. Ameer, Novel citric acid-based biodegradable elastomers for tissue engineering. Advanced Materials, 2004. 16(6): p. 511-516.

Seed #3

Analysis and Design of Genetic and Metabolic Control Systems of Bacterial Cells

Adilson E. Motter, physics
John F. Marko, biochemistry, molecular biology & cell biology/physics (joint)

Molecular biology permits custom programming of cells to carry out specific tasks, such as synthesis of specific biomolecules or modification of molecules in the extracellular environment. Further examples include formation of multicellular structures or sending chemical or optical signals in response to detection of specific molecules.

The bacterium Escherichia coli, for which there exists a staggering array of genetic engineering methods and genomic data, is well suited for such tasks. Efforts at bioengineering of E. coli depend on understanding unresolved basic questions of the mechanisms underlying control of gene expression (i.e., modulation of which genes are expressed at any given time, largely through DNA-protein interactions on the chromosome) and metabolic processes (i.e., the biochemical reaction pathways through which the basic molecules of a cell are processed).

The overall objective of this joint project between the Motter and Marko labs is to biologically engineer bacterial cells, and design them to perform specific tasks and to produce specific materials. Two complementary projects focus on understanding mechanistic aspects of gene expression and metabolic processes in E. coli. Key strengths of the project are the complementary abilities of groups in the areas of theoretical study of metabolic and genetic networks of E. coli (Motter), study of information in genetic sequences (Motter), theoretical and experimental study of protein-DNA interactions at the single-molecule level (Marko), experimental study of chromosome structure and function (Marko), and theoretical and experimental study of soft materials including supramolecular assemblies of biomolecules (Marko).

Components of the genetic and metabolic system of the bacterium E.coli explored in this project. Cyan arrows highlight protein-gene interactions (D->c), protein-protein interactions (E<->F), and the enzymatic catalysis of metabolic reactions (B->R1, G->R5). In this example, A...G represent proteins encoded by genes a...g, respectively, and R1...R6 are enzyme-catalyzed metabolic reactions interconnected by metabolic compounds (red arrows).

Seed #4

Electrostatically "Patchy" Nanoparticle Coatings for Applications in Biomaterials and Flexible Electronics

Bartosz Andrzej von Poray Grzybowski, chemical and biological engineering

This interdisciplinary research aims to develop a new class of “patchy” nanoparticle coatings for uses in biocompatible surfaces and in flexible electronics. The work builds on this research group’s recent progress in using electrostatic interactions to drive self-assembly of charged nanoscopic components into various types of supra-structures.1-3
In this work, the group is using nanoscale electrostatics to deposit robust, mono- and multilayer coatings composed of different types of charged nanoparticles on elastomeric/flexible substrates. By adjusting the composition and thickness of these films, they will be able to tailor and adjust their properties including bioresistance, bacteriostaticity and electrical conductance.

References
1. A.M. Kalsin, M. Fialkowski, M. Paszewski, S.K. Smoukov, K. Bishop, B.A. Grzybowski Science, 312, 420 (2006).
2. A.M. Kalsin, M. Paszewski, A. Pinchuk, G.C. Schatz, B. A. Grzybowski Nano Lett., 6, 1896 (2006).
3. A. M. Kalsin, A. Pinchuk, B.Kowalczyk, R. Klajn, B. A. Grzybowski J. Am. Chem. Soc., 10.1021/ja0642966

Selected Research Highlights:

Network-based Design of Microbial Strains for the Production of Biomaterials

A.E. Motter, T. Nishikawa, N. Gulbahce , E. Almaas , and A.-L. Barabasi

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Moldable Supraspheres Made of Metal Nanoparticles

R. Klajn, K.J.M. Bishop, M. Fialkowski, M. Paszewski, C.J. Campbell, T.P. Gray, B.A. Grzybowski

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