Nanobiology: New Methods and New Materials

The heterogeneity found in many cell types, including stem cells and cancer cells, has greatly inspired research in single-cell gene and protein profiling for discovering the origin of heterogeneity and its role in cell fate decisions. A cell function is pertinent to the cell communication with surrounding cells and extracellular matrix. Quantitative analysis of protein and gene expression levels in individual communicative cells in the context of their native environment is essential for probing the spatiotemporal dialog between the same and different populations of cells. In many cases, the target cells are the side population cells in a complex cell community. Thus the ability to quantify and manipulate proteins and genes against a specific cell is critical to understanding cell-cell interactions in the complex community. To address these challenges we developed AFM-based methods, which were applied to in-situ quantitative analysis of protein and gene expression at the sub-cellular and cellular levels in complex natural environment for identifying sub-population cells within a cell colony and unveiling the signal transduction upon cell-cell interactions. A two-tier AFM assay, based on the use of heterobifunctional photo-cleavable cross linkers, was also established to permit guided protein delivery and subsequent high-resolution imaging at the same local area, thus opening up the possibility of monitoring protein function and drug effectiveness in live cells. The effect of collagen based natural and composite nano-materials on cell development and tissue function will also be introduced.