Imaging Receptors Inside Living Cells
Being able to see chemistry happen inside living cells in real time provides important understanding about how the cells function. However, imaging the behavior of cellular receptors that respond to small molecules is especially challenging when they are inside a cell rather than on the surface. A new approach to find compounds that can locate these intracellular receptors in living cells has been developed by scientists at Lawrence Berkeley National Laboratory in collaboration with scientists at the University of California, Berkeley, Ames Laboratory, and National University of Singapore. Candidate compounds are initially screened for the ease with which they enter cells and then for their rapid clearance out of the cells if they are not bound inside the cell (i.e., their ‘non-stickiness’). The screening is carried out in mammalian cells and the non-sticky compounds are then used to study complex multicellular systems such as plant roots using live-cell microscopy. A structure and flux-function co-relationship study was carried out to construct an atlas of structure-flux responses, the first of its kind. Radiolabeling studies using this information have enabled scientists to image gene expression in the living cell with positron emission tomography (PET).
Nath, S., V. A. Spencer, J. Han, H. Chang, K. Zhang, G. V. Fontenay, C. Anderson, J. M. Hyman, M. Nilsen-Hamilton, Y.-T. Chang, and B. Parvin. 2012. “Identification of Fluorescent Compounds with Non-Specific Binding Property via High-Throughput Live Cell Microscopy,” PLoS One, DOI: 10.1371/journal.pone.0028802.