Nanoplasmonic imaging reveals real-time protein secretion

Date:
April 11, 2023
Source:
Ecole Polytechnique Fe'de'rale de Lausanne
Summary:
Researchers have used a nanoplasmonics approach to observe the
real-time production of cell secretions, including proteins and
antibodies; an advancement that could aid in the development of
cancer treatments, vaccines, and other therapies.


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FULL STORY ==========================================================================
Cell secretions like proteins, antibodies, and neurotransmitters play
an essential role in immune response, metabolism, and communication
between cells.

Understanding cell secretions is key for developing disease treatments,
but current methods are only able to report the quantity of secretions,
without any detail as to when and where they are produced.


==========================================================================
Now, researchers in the BIOnanophotonic Systems Laboratory (BIOS) in
the School of Engineering and at the University of Geneva have developed
a novel optical imaging approach that gives a four-dimensional view of
cell secretions in both space and time. By placing individual cells into microscopic wells in a nanostructured gold-plated chip, and then inducing
a phenomenon called plasmonic resonance on the chip's surface, they are
able to map secretions as they are being produced, while observing cell
shape and movement.

As it provides an unprecedentedly detailed view of how cells function and communicate, the scientists believe their method, recently published
in Nature Biomedical Engineering, has "tremendous" potential for
pharmaceutical development as well as fundamental research.

"A key aspect of our work is that it allows us to screen cells
individually in a high-throughput fashion. Collective measurements of the average response of many cells do not reflect their heterogeneity...and
in biology, everything is heterogeneous, from immune responses to
cancer cells. This is why cancer is so hard to treat," says BIOS head
Hatice Altug.

A million sensing elements At the heart of the scientists' method is a 1 cm2nanoplasmonic chip composed of millions of tiny holes, and hundreds
of chambers for individual cells. The chip is made of a nanostructured
gold substrate covered with a thin polymer mesh.

Each chamber is filled with a cell medium to keep the cells alive and
healthy during imaging.

"Cell secretions are like the words of the cell: they spread out
dynamically in time and space to connect with other cells. Our technology captures key heterogeneity in terms of where and how far these 'words'
travel," says BIOS PhD student and first author Saeid Ansaryan.

The nanoplasmonics part comes in thanks to a light beam, which causes
the gold electrons to oscillate. The nanostructure is engineered so
that only certain wavelengths can penetrate it. When something --
like protein secretion - - occurs on the chip's surface to alter the
light passing through, the spectrum shifts. A CMOS (Complementary Metal
Oxide Semiconductor) image sensor and an LED translate this shift into intensity variations on the CMOS pixels.

"The beauty of our apparatus is that the nanoholes distributed across the entire surface transform every spot into a sensing element. This allows
us to observe the spatial patterns of released proteins irrespective of
cell position," says Ansaryan.

The method has allowed the scientists to get a glimpse of two essential cellular processes -- cell division and cell death -- and to study
delicate antibody-secreting human donor B-cells.

"We saw the cell content released during two forms of cell death,
apoptosis and necroptosis. In the latter, the content is released in an asymmetric burst, resulting in an image signature or fingerprint. This
has never before been shown at the single-cell level," Altug says.

Screening for cell fitness Because the method bathes the cells in a
nutritious cell medium, and does not require the toxic fluorescent labels
used by other imaging technologies, the cells under study can easily be recovered. This gives the method great potential for use in developing pharmaceutical drugs, vaccines, and other treatments; for example, to
help researchers understand how cells respond to different therapies at
the individual level.

"As the amount and pattern of secretions produced by a cell are a proxy
for determining their overall effectiveness, we could also imagine immunotherapy applications where you screen patient immune cells to
identify those that are most effective, and then create a colony of
those cells," says Ansaryan.

* RELATED_TOPICS
o Health_&_Medicine
# Stem_Cells # Lymphoma # Immune_System # Lung_Cancer #
Brain_Tumor # Nervous_System # Cancer # Sickle_Cell_Anemia
* RELATED_TERMS
o Stem_cell_treatments o Adult_stem_cell o
Monoclonal_antibody_therapy o Stem_cell o Colorectal_cancer
o Cancer o Protein o DNA

========================================================================== Story Source: Materials provided by
Ecole_Polytechnique_Fe'de'rale_de_Lausanne. Original written by Celia Luterbacher. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Saeid Ansaryan, Yen-Cheng Liu, Xiaokang Li, Augoustina Maria
Economou,
Christiane Sigrid Eberhardt, Camilla Jandus, Hatice Altug. High-
throughput spatiotemporal monitoring of single-cell secretions via
plasmonic microwell arrays. Nature Biomedical Engineering, 2023;
DOI: 10.1038/s41551-023-01017-1 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/04/230411105840.htm

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