Nanostructures and imaging tools for detection of cancer cell surface markers

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We will create nanostructures and polymer materials, explore self-assembly, to improve surface binding specificity and enable high resolution imaging of cell membranes and their constituents. We aim to employ chemically and mechanically controlled surface functionalization for probing fundamental problems in biophysical chemistry of cellular processes, establishing a novel platform for bio-imaging, protein adhesion and cell mechanics. Controlled surface chemistry will introduce molecular recognition and specificity. Integration with cell mechanics probed by atomic force microscopy (AFM) will bring new insights into cellular processes such as force transduction across cell membranes at the 50 nm length scale, which is not possible to probe for heterogeneous systems using existing approaches. In particular, our newly developed self-assembly and seeding growth method is suitable for low-cost mass-manufacturing of ordered nanoparticle arrays, and the proposed hybrid nanostructure using similar approach will provide high sensitivity for plasmonic enhanced subwavelength imaging and sensing application. To integrate this novel nanoparticle based platform with the understanding on mechanical properties of cancer cells at the molecular resolution is the long term goal of our research, which will establish the structure-property-function relationship that enable the design of new materials and devices for cancer diagnosis and prognosis, and fulfill the requirement of new metrologies incisive on the nanoscale. Three research areas with specific projects are proposed in this program, namely, Area 1. Mechanical detection of the acute promyelocytic leukemia (APL) cell membranes: (1a). Fabrication of microwells for non-adherent APL cells; (1b). Elasticity measurements of drug treated and non-treated APL cell line (NB4) cells; (1c). Therapeutic treatments and viability evaluations on drug resistant cells; (1d). Mechanical detection on APL patient samples. Area 2. Single molecule force spectroscopy (SMFS) study of the retinoic acid (RA) receptor and retinoic acid binding interactions: (2a). Binding interaction between all trans retinoic acid (ATRA) and RA receptors; (2b). Unbinding forces of the individual complexes of the drug-RA receptor and the ligand-RA receptor. Area 3. Nanostructure platform for antibody, membrane protein and cell surface marker detection: (3a). Hybrid nanoparticle (NP) arrays for anti-surface marker (CD38) detection; (3b). Local surface plasmon resonance coupled fluorescence for quantification of the surface markers (CD38 and CD56). The outlined program will include the training of two graduate and five undergraduate students. The current undergraduate and Ph.D students will also benefit from the team working environment and scientific discussions proposed in this program. All students will be trained with expertise in surface chemistry, self-assembly, and advanced atomic force microscopy and integrated fluorescence microscopy for membrane characterizations and sensing applications. The full potential of using nanostructures and novel materials in biophysical chemistry and cell biology is predicted to be attainable when combined with advanced microscopy and spectroscopy techniques. The proposed multi-modal imaging and single molecule mechanical detection approach will allow cellular structures to be identified by fluorescence, imaged at high resolution using AFM, and mechanically probed by single molecule force spectroscopy. Complementary to conventional ensemble measurements, surface chemistry and scanning probe microscopy based techniques will provide new pioneering insights in understanding the molecular principles of cancer and nanomedicine.