Control over reversible biological states, such as the stepwise progression of cells toward apoptosis before the point of no return, holds promise for eradicating mankind's greatest killers, including cancer, diabetes and heart disease. A key mutable biological process that regulates cell survival and function is the formation of the dynamic cytoskeleton, in which microtubules play a leading role. Microtubules regulate intracellular transport, motility, shape, membrane trafficking, subcellular organization, cell division and responses to the environment. Not surprisingly, microtubules have become a main target for disease therapeutics, especially in cancer. Molecular technologies that increase our local and cell-wide understanding of dynamic microtubule processes are essential for gaining control over processes that depend on microtubules, such as reversible stages in cell death. A set of unique nanotech tools has already developed in our group and enables us to precisely address the aims outlined in the NIH nanomedicine initiative, which is """"""""... to characterize quantitatively the molecular scale components ...in living cells to improve human health"""""""". We will integrate novel nanotech-based technologies into a generic platform for interrogating and controlling a wide class of cellular functions. These technologies include 1) optoelectronic tweezer technology that can precisely move cells in a programmable bio-reactor system. 2) AFM modified with multiwalled carbon nanotubes that can measure nanoscale molecular interactions occurring at the cell surface. 3) Metallo-dielectric multilayer superlens that can reach an ultimate spatial resolution of 20-30nm. 4) An """"""""intelligent"""""""" drug which selectively targets diseased cells such as cancer cells. Coupling these nanotechnologies possessing molecular level resolution, we will be able to directly visualize and control key molecules towards enhanced intervention over processes such as apoptosis, and elucidate new targets or mechanisms for therapy.
