Grants and Contracts per year
Grants and Contracts Details
Adsorption of Treponema Pallidum Protein to Functionalized Alkanethiol Self- Assembled Monolayers for Improving Biocompatibility PI: Kimberly W. Anderson University of Kentucky This proposal addresses the need for biocompatible surfaces for use as bloodcontacting devices. The proposed study investigates the use of antigenic protein disguise to create biocompatible systems. Intellectual Merit. Clinical uses of blood-contacting devices are becoming more common. While many of these devices have been successfully used in patients for many years and are judged to be therapeutically beneficial, their performance is less than optimal. Almost immediately upon implantation in the body, blood-contacting materials become completely coated with proteins and this leads to attachment of cells in the body. Aggregated platelets combine with protein on the surface and lead to formation of thrombi which can cause significant problems downstream and also hinder the performance of the device. The overall objective of this investigation is to test the feasibility of using a Treponema pallidum protein, Tp0483 bound to human plasma fibronectin to create a hemocompatible surface by utilizing antigenic disguise. Treponema pallidum is a spirochete bacterium which causes syphillis. It has been shown that this bacterium binds soluble dimeric fibronectin and some investigators believe that the bound fibronectin serves an an antigenic disguise for the bacterium. Recently, the protein responsible for binding soluble fibronectin, Tp0483 has been identified, expressed and purified. In this proposed study, Tp0483 will be adsorbed to surfaces using self-assembled monolayers and the adsorption of fibronectin (FN) and a fibronectin fragment FN 7-10 will be investigated using surface plasmon resonance. In addition, the mechanism of adsorption of the FN and FN 7-10 to the Tp0483 will be studied using Atomic Force Microscopy (AFM). It is hypothesized that FN and/or FN 7- 10 will bind to the Tp0483 protein through the RGD binding site and adhesion of cells and other proteins will be inhibited due to the lack of RGD binding site and also due to the body recognizing the FN coated surface as a natural, physiological system. It is also hypothesized that FN 7-10 will inhibit protein and cell binding better than the total FN due to lack of other binding sites on the fragment. Finally, the hemocompatibility of the surfaces with and without Tp0483 and/or FN and FN 7-10 will be investigated by using in-vitro techniques. Broader Impacts. Many different approaches have been used to create bloodcompatible surfaces and while these processes have been shown to improve bloodcompatibility, the creation of a wholly hemocompatible surface has, thus far, been unachievable. This is the first study of its kind where antigenic disguise will be used to create hemocompatible surfaces. If funded, this project has the potential of greatly impacting the use of implantable devices in clinical research. In addition, information obtained on mechanisms of FN binding to TP0483 will provide a better understanding as to how Treponema pallidum uses this protein for antigenic disguise. While this study focuses specifically on using the protein, Tp0483 for improving compatibility of bloodcontacting materials, the results will form the basis for future studies where other naturally occurring proteins known for antigenic disguise can be studied. The proposed research combines expertise in molecular aspects of proteins and cellular bioengineering. In addition to the graduate student supported on this project, undergraduate students as well as high school students will have the opportunity to participate in this research and receive multidisciplinary training in engineering and biology.
|Effective start/end date||8/1/07 → 7/31/12|
- National Science Foundation: $314,625.00
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- 1 Finished