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Study of Self-assembling Oligopeptides

Self-assembling oligopeptides are new biomaterials, which have many potential applications in biomedical and pharmaceutical areas. The biocompatibility and biodegradability of these peptides make them ideal candidates as matrixes in tissue engineering and carriers in drug delivery systems. To understand the self-assembly mechanism, it is necessary to study the conditions under which the oligopeptides aggregate and further form fibril networks.

Characterization of the Aggregation of Self-assembling Oligopeptides
To apply the self-assembling oligopeptides to the construction of nanostructures for biomedical applications, an understanding of the factors that control molecular self-assembly are critical. There are many factors affecting the aggregation behavior. The study of concentration and time dependence shows that there exists a Critical Aggregation Concentration (CAC), which provides important information as to when aggregation starts. The study of pH and the amino acid sequence dependence shows that the nanostructure of oligopeptide aggregates can be controlled by adjustment of solution conditions. Substrate dependence of the nanostructure is also important.

Techniques used in this project are,
· Atomic Force Microscopy (AFM) : to investigate the nanostructures of the self-assembling oligopeptides
· Electrochemical AFM : to characterize the substrate dependence
· In-situ AFM experiment and Nuclear Magnetic Resonance (NMR) : to study the dynamic mechanism of self-assembly
· Scanning Electron Microscopy (SEM) : as a complementary method to AFM
· Axisymmetric Drop Shape Analysis-Profile (ADSA-P) : to measure the interfacial tension of oligopeptide solutions
· Fluorescence and Light Scattering : to investigate the aggregation in bulk phase
 

Self-assembling Oligopeptides as a carrier for drug delivery
The biocompatibility and biodegradability make self-assembling oligopeptides ideal materials as a carrier for drug delivery. However, many conditions, such as encapsulating, targeting, releasing, and stability, need to be understood before applying these materials. In this project, the complex formation, stability, and release properties of oligopeptides are investigated by using AFM, ADSA-P, Fluorescence and Light Scattering. In the near future, real drugs will be adopted as hydrophobic additives, and an in vitro environment will be built for release studies.

Irreversibility of the Aggregation of Self-assembling Oligopeptides
There are evidence showing that the self-assembling oligopeptides form aggregates and fibers in aqueous solutions. Understanding the degradation of the nanostructures is crucial to control and design the oligopeptides for biomedical and pharmaceutical applications. The study of irreversibility also tells to how and when these oligopeptides aggregate, which helps understand the self-assembly mechanism. This project is to investigate the time dependent behavior of aggregation by comparing dilute samples with freshly prepared one through AFM, ADSA-P, and Fluorescence Light Scattering.

Modeling of the Self-assembly
The understanding of mechanism of a self-assembly system is critical to control and design the nanostructures and supramolecular structures. However, very few studies in this area have been done. Pictorial modeling of the self-assembly of oligopeptides has been proposed, and further work will be using computer simulation.