Cell secretions such as proteins, antibodies, and neurotransmitters play essential roles in immune response, metabolism, and cell to cell communication. Understanding cellular secretions is key to developing disease treatments, but current methods are only able to report the amount of secretions without any details about when and where they are produced.
Now researchers at the BIOnanophotonic Systems Laboratory (BIOS) at the Faculty of Engineering and the University of Geneva have developed a new optical imaging approach that provides a four-dimensional view of cell secretions in both space and time.
By placing individual cells in microscopic wells in a nanostructured gold-plated chip and then inducing a phenomenon called plasmonic resonance on the surface of the chip, they are able to map the secretions as they are produced, while observing the shape and movement of the cells.
4D view of cell secretions
The basis of the scientists’ method is a 1 cm2 nanoplasmonic chip composed of millions of small holes and hundreds of cells for individual cells. The chip is made of a nanostructured gold substrate covered with a thin polymer mesh. Each chamber is filled with cell medium to keep the cells alive and healthy during imaging.
“Cell secretions are like a cell’s words: they spread dynamically in time and space to connect with other cells. Our technology captures a key heterogeneity in where and how far these ‘words’ travel,” says BIOS PhD student and first by Saeid Ansaryan.
The nanoplasmonic part comes from a light beam that causes gold electrons to oscillate. The nanostructure is designed so that only certain wavelengths can penetrate it. When something on the surface of the chip—like protein secretion changes the light passing through, the spectrum shifts.
“The beauty of our device is that the nanoholes distributed over the entire surface transform each site into a sensing element. This allows us to observe the spatial patterns of released proteins regardless of the cell’s position,” says Ansaryan.
This method allowed the scientists to look into two basic cellular processes cell division and cell death and study the delicate human donor B-cells secreting antibodies.
“We have seen cellular contents being released during two forms of cell death, apoptosis and necroptosis. In the latter, the contents are released in an asymmetric burst, resulting in an image signature or fingerprint. This has never been shown before at the single-cell level” says Altug.
Screening for cell fitness
Ansarian says Because the method bathes the cells in a nutrient cell medium and does not require the toxic fluorescent labels used by other imaging technologies, the cells being studied can be easily obtained. for example, to help researchers understand how cells respond to different therapies at an individual level.
Because the amount and pattern of secretions produced by a cell is a proxy for determining its overall effectiveness, we could also envision immunotherapy applications where you test a patient’s immune cells to identify the ones that are most effective and then create a colony of those cells.
Written by: Vaishali Verma
