Lighting up the changes of plasma membranes during apoptosis with fluorescent probes

Plasma membranes, as the network for transferring information and constituents between cells and their microenvironment, play important roles in physiological and pathological processes. As the first defensive barriers of cells, cell membranes take further actions through changes in shapes, morphologies or components once they sense damages from exterior poison stimulations. Thus, the changes of plasma membranes are the direct indication for apoptosis induced by drugs, and non-destructive visualization of these changes is of great significance. Various fluorescent probes for real-time and in situ monitoring these changes of plasma membranes have been explored for more than 20 years. However, a concise review on this specific and important topic is still lacking, which may hamper the development of this field. In this review, the typical fluorescent probes for visualization the changes of plasma membranes during apoptosis in the past decades have been summarized. The representative examples have been classified into five categories according to the biological changes, which included the changes of phosphatidylserine (PS), changes in membrane composition, changes in membrane permeability, changes in morphologies and lipid order in plasma membranes. The basic principle, design strategies, sensing mechanisms and the applications of these fluorescent sensors that have been achieved were discussed. The perspectives and challenges with respect to this field were also presented. We anticipated that this review can promote the development of the probes for sensing the changes of plasma membranes during apoptosis, and facilitate the studies of drug discovery and other relative biomedical fields.