Fixing cells with light and DNA-binding fluorophores

Light has become of paramount importance for the spatiotemporal control of cell labeling, activity and death. We found that palmatine, a DNA-binding alkaloid, mediates the fixation of live cells upon visible light irradiation. Fixation takes a few seconds or minutes depending on the power used, is accompanied by nuclear fluorescent labeling in target cells, exhibits a high degree of control from cell islets to single cells, yielding cells with intact nucleus and membrane boundaries. 'Optofixation' relies on palmatine-DNA interaction, singlet oxygen photogeneration and lipid peroxidation, producing fixing levels of endogenous aldehydes. We also establish that many commonly used nuclear dyes exhibit optofixation properties across the UV-far red spectrum. Comprising the straightforward inactivation and labeling of native target cells by small fluorophores, this unprecedented, comparatively simple technology has the potential for major applications in biological research.