Victoria Garcia Sakai

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Duration in group: 2005 - 2007

Research Summary

My research in the Maranas group involves using the power and sensitivity of these unique small particles, neutrons. Their lack of charge makes them ideal candidates for direct interaction with the atomic nucleus, yielding information on the atomic properties of materials. The technique used for this purpose is called Neutron Scattering and measurements are performed in a nuclear reactor facility, in my case the Center for Neutron Research at NIST, Maryland. Neutron scattering is used to determine structural and dynamic information of a wide variety of materials: biological, polymeric, magnetic. Scattering spectrometers simultaneously resolve information in time (from 10fs to 0.1us) and in space (up to 100 nm). They tell you how fast atoms move and how far the move at any given conditions (temperature, pressure etc.). Neutron scattering is an ideal partner to molecular dynamic simulation, which also resolves in time and space simultaneously. Neutrons interact very differently with hydrogen and deuterium atoms which allow us to label different groups in a molecule. For example, if we are interested in the motion of water in a protein solution, we deuterate the protein and "see" only the motion of water molecules.

So, why would we like structural and dynamic information? Here are 3 problems that I am working on:

Polymer Science: To understand the effect of blending on the dynamics of polymers.

Consider plexiglass [polymethyl methacrylate, PMMA] which has a high glass transition temperature. As a result it needs to be processed at a temperature around 220 C and ensuring that the degradation temperature (240 C) is not reached. To increase this small processing temperature window, a small amount of a low glass transition temperature polymer, like polyethylene oxide [PEO], can be added. In the mixture the mobility of PMMA chains is higher at a lower temperature than in the pure melt, facilitating processing without altering the final material properties. This change in the mobility of the PMMA chains caused by the addition of PEO is studied using a number of neutron scattering spectrometers. We use the time-of-flight and the backscattering spectrometers to follow the motion of protons on the polymer chains as a function of time (picoseconds and nanoseconds respectively). We us the neutron-spin echo spectrometer to follow how each atom in the blend moves relative to every other atom.

Biosensors: To structurally and dynamically characterize a potential in vivo glucose biosensor.

Consider the 176 million people that are affected by diabetes. At present administration of insulin relies on electrochemical sensors which involve painful finger-pricking blood sampling. An alternative method entails monitoring glucose levels subcutaneously. A biosensor being researched involves the binding/unbinding of a protein, Concanavalin A [Con A], to a polysaccharide, dextran. In the presence of glucose, dextran is displaced from the binding sites in an amount proportional to the amount of glucose. Detection occurs through fluorescence signal changes resulting from the binding/unbinding process. For potential in vivo applications of this method, the system is encapsulated in micro-spheres of a hydrogel of biocompatible polyethylene glycol [PEG]. The hydrogel consists of PEG swollen in water. When the system is enclosed in the micro-spheres, the success rate for glucose detection is not 100%. Neutron scattering is being used to determine the effect of the hydrogel on the interactions between the two molecules. The PEG matrix should neither inhibit the diffusion of glucose in and out of the hydrogel nor hinder association/dissociation of Con A and dextran.

Figure 1- Schematic of the Con A/dextran/glucose system. FRET stands for fluorescent resonance energy transfer.

Cryopreservation: To identify the mechanism by which disaccharides help cryopreserve biological molecules.

Trehalose, a sugar found in animals that endure cold temperatures, is known to have a stabilizing effect on biological membranes with application in food, biomedical, pharmaceutical and cosmetic industries. In addition, trehalose lowers the melting temperature of bilayer membranes preventing leakage during freezing and drying of cells. Unfortunately, the exact mechanism by which disaccharides preserve biological systems is not well understood. Neutrons can be used to study the atomic-level interactions between trehalose and a model lipid bilayer. Specifically, structural differences of the bilayer in the absence/presence of the sugar can be detected and changes in mobility of the sugar, lipid and residual water will give information on the interactions between the molecules.