Biophysical Properties of Tubulin and Microtubules and Their Nano-Biotechnology Potential

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This project is focused on the biophysical properties of one of the key proteins in plant and animal cells: tubulin and its polymerized form, microtubules. (Polymers are molecular structures that are assembled out of repeating subunits.)******Hundreds of tubulin genes from various species (including human) have been sequenced, which provides an enormous amount of untapped information about evolutionary changes in the structure and the biophysical/biochemical properties of this protein. We intend to use this information in our study. We will analyze all available tubulin sequences and construct 3D models of the protein based on the known templates for tubulin found in the Protein Data Bank. We will also investigate several biophysical properties of microtubules such as electrostatic charges and their spatial distribution. The interactions of the key drugs known to bind to tubulin will be investigated for the specificity of tubulin variants. This will enable us to create a map of interactions that can be affected by variations in the sequences of tubulin, which are known to occur in different cell types. Building off our previous work we will determine how specific amino acid changes between variants of tubulin affect the binding affinity between neighbouring tubulin molecules in the microtubule structure. This will inform us about both the static and dynamic mechanical properties of microtubules constructed from variants of tubulin. These results will fill a gap in the existing knowledge about the structure-to-function relationship of tubulin.******In addition, we plan to continue our investigations of the electric conduction properties of microtubules, in collaboration with the Shankar group at the University of Alberta, to conclusively determine single microtubule conductance, capacitance, and possibly inductance (these are electrical properties), due to ionic current flows around microtubules. We intend to extend this nano-scale experimentation and couple it with computer modeling to study individual microtubules under various conditions of pH, ionic concentrations, temperature variations, and the presence of microtubule-associated proteins. Here, we plan to quantify these effects and to include AC conduction measurements in the range between 1 kHz and 1 MHz. This will enable the construction and characterization of complex architectures intended as micro-circuitry built from proteins and protein polymers. The ultimate objective of this aim is to provide a framework for creating nano-bio-electronic elements and combinations, for application as biodegradable and evolvable computing devices in the future.******Our final interest in this project is to simulate the response of tubulin dimers to electromagnetic frequencies in several ranges (kHz, MHz, GHz and THz), in order to determine the sensitivity of tubulin structure to these fields, both for basic and applied biophysics considerations.