If we could continuously monitor conditions inside individual cells, we would open a host of new research tools and diagnostic modalities. And that is what investigators from the National Institute of Standards and Technology (NIST) and the National Institute of Allergy and Infectious Diseases (NIAID) are trying to accomplish. The biophysics researchers analyzed how bioconjugated nanocrystals, or quantum dots, fluoresce in various environments over an extended period of time. And since these particles can be attached to just about any protein, they might offer a bright future for intracellular monitoring.
For their recent study, the team focused primarily on characterizing quantum dot properties, contrasting them with other imaging techniques. In one example, they employed quantum dots designed to target a specific type of human red blood cell protein that forms part of a network structure in the cell’s inner membrane. When these proteins cluster together in a healthy cell, the network provides mechanical flexibility to the cell so it can squeeze through narrow capillaries and other tight spaces. But when the cell gets infected with the malaria parasite, the structure of the network protein changes.
“Because the clustering mechanism is not well understood, we decided to examine it with the dots,” says NIAID biophysist Fuyuki Tokumasu. “We thought if we could develop a technique to visualize the clustering, we could learn something about the progress of a malaria infection, which has several distinct developmental stages.”
The team’s efforts revealed that as the membrane proteins bunch up, the quantum dots attached to them are induced to cluster themselves and glow more brightly, permitting scientists to watch as the clustering of proteins progresses. More broadly, the team found that when quantum dots attach themselves to other nanomaterials, the dots’ optical properties change in unique ways in each case. They also found evidence that quantum dot optical properties are altered as the nanoscale environment changes, offering greater possibility of using quantum dots to sense the local biochemical environment inside cells.
Image: Human red blood cells, in which membrane proteins are targeted and labeled with quantum dots, reveal the clustering behavior of the proteins. The number of purple features, which indicate the nuclei of malaria parasites, increases as malaria development progresses. The NIST logo at bottom was made by a photo lithography technique on a thin film of quantum dots, taking advantage of the property that clustered dots exhibit increased photoluminescence. (White bars: 1 μm; red: 10 μm.)
Press release: Small Nanoparticles Bring Big Improvement to Medical Imaging …
Abstract in WIREs Nanomedicine and Nanobiotechnology: Probing dynamic fluorescence properties of single and clustered quantum dots toward quantitative biomedical imaging of cells
