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 using a photo lithography technique on a thin film of quantum dots, taking advantage of the property that clustered dots exhibit increased photoluminescence. (Credit: H. Kang/NIST and F. Tokumasu/NIAID.)
New research from the National Institute of Standards and Technology (NIST; Gaithersburg, MD) and the National Institute of Allergy and Infectious Diseases (NIAID; Bethesda, MD) enables scientists to observe and analyze activities that occur over hours or even days inside cells, opening the door to solving many mysteries associated with molecular-scale events.
The joint NIST/NIAID research team has discovered a method of using quantum dots to illuminate the cellular interior to reveal these slow processes. A type of nanoparticle, quantum dots are semiconductor particles that can be coated with organic materials tailored to be attracted to specific proteins within the part of a cell a scientist wishes to examine. When exposed to light, the dots glow.
“Quantum dots last longer than many organic dyes and fluorescent proteins that we previously used to illuminate the interiors of cells,” explains biophysicist Jeeseong Hwang, the NIST team leader. “They also have the advantage of monitoring changes in cellular processes while most high-resolution techniques like electron microscopy only provide images of cellular processes frozen at one moment. Using quantum dots, we can now elucidate cellular processes involving the dynamic motions of proteins.”
The NIST/NIAID study focused primarily on characterizing quantum dot properties, contrasting them with other imaging techniques. In one experiment, the team 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 that 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 and glow more brightly, permitting scientists to watch as the clustering 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 a greater possibility of using quantum dots to sense the local biochemical environment inside cells.
“Some concerns remain over toxicity and other properties,” Hwang says, “but altogether, our findings indicate that quantum dots could be a valuable tool to investigate dynamic cellular processes.”
For detailed information on this research, see Probing Dynamic Fluorescence Properties of Single and Clustered Quantum Dots Toward Quantitative Biomedical Imaging of Cells.
Tags: nanoparticles, Quantum Dots
