Live Cell Microscopy: A Physical Chemistry Approach.

Probing dynamics of intracellular components using physical chemistry techniques is a remarkable bottom-up approach for understanding the structures and functions of a biological cell. In this "Feature Article", we give an overview on local polarity, solvation, viscosity, acid-base property, red-ox processes (thiol-disulfide exchange), and gene silencing at selected intracellular components inside a live cell. Significant differences have been observed between cancer cells and their noncancer counterparts. We demonstrate that thiol-disulfide exchange, calcium oscillation, and gene silencing are manifested in time dependence of fluorescence intensity. We show that fluorescent gold nanoclusters may be used in drug delivery (e.g., doxorubicin) and selective killing of cancer cells. Further, we discuss dynamics and structural changes of DNA quadruplexes and i-motifs, induced by different external conditions (e.g., pH) and additives (e.g., K+ and other target specific small molecules). We demonstrate that peptidomimetic analogues have high specificity over double-stranded DNA for binding with i-motifs and G-quadruplexes. These results may have significant biological implications.