Extracting the contents of living cells

Abstract

Being able to monitor cells at different times is key to tracking fundamental cellular processes such as differentiation and cellular senescence, as well as disease progression and the effectiveness of drugs. However, most approaches are destructive and involve lysing the cells. Different time points can be studied by using parallel cell cultures, but the inferred changes could also be the result of cell heterogeneity (1, 2). Techniques for extracting small quantities of the cytosol for long-term tracking of a single cell's response must manipulate picoliter-scale volumes, maintain high cell viability, and give an accurate reflection of the cell's multiple biological components, as well as avoid influencing the ongoing development of the cell (see the figure) (1, 3). Cao et al. approached this problem by culturing cells on top of a random arrangement of hollow cylinders, which they call nanostraws (2). These 150-nm-diameter alumina tubes can sample 5 to 10% of proteins, messenger RNA (mRNA), and small molecules from the cells but only reduce cell viability by ∼5%. Their approach allows intracellular sampling and characterization at multiple time points from the same cells to track changes.