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Humboldt-Universität zu Berlin - Institut für Biologie

Summary

Cells in our body communicate with each other by sending signals in the form of ions and proteins. Therefore, proteins and ions that are “secreted” from the cells are the messengers to the neighbouring cells. The receivers of these “coded message” can quickly respond to the delivered signal by adopting their cellular process and send new information to other cells about these changes, with a new “encoded signal”. This is how our whole cellular organism communicates and is the working principle of our functional systems, such as immune system, brain communication, digestive, muscular and visual systems and etc. Most of the diseases in our body is recognized by this mechanism. For example, if our immune cells do not receive the expected signal from a pathogen, they start to send signals to the other immune cells about the threat and demand for action. Any dysfunction in these communication routes can cause severe problems that lead to a variety of diseases, such as cancer and autoimmunity.

 

Cell membrane is the gate for the trafficking of ions and biomolecules into and out of the cell. It is very important to study secretion of cell products (secretome) at this gate, as it will allow us to understand the cell response to various stimulations, and perhaps help us to reveal the “code” for various responses. Therefore, recording the secrotome from individual cells is of great importance.

 

However, monitoring the ions and biomolecules secreted from the cell is not an easy task. Scientists have developed multiple techniques to record secrotome of the cell, but so far none of the techniques allowed us to dynamically monitor the secretion of ions and biomolecules from single cells. In a recent study, together with the Laboratory of Biosensors and Bioelectronics at ETH Zurich (Prof. Vörös), researchers have introduced a new technique which allows detection of ions and biomolecules in arbitrary locations both inside and outside of the cell. The introduced platform is based on a nanopore device that is integrated in a fluidic microchannel embedded in an Atomic Force Microscope (AFM), and is called Scanning Nanopore Microscope. This microscope is able to scan and image cells with a high resolution similar to AFM. However, the integrated nanopore at the apex of the AFM cantilevers brings new advantages to this system, such as measuring ion conductance with high sensitivity. A nanopore sensor works based on the mobility of ions at the nanopore region and is very sensitive to minor changes in the ionic current. Translocation of ions and other biomolecules through the nanopore creates transient fluctuation in the ionic current which can be further analyzed to characterize the types of the translocating molecules.

Scanning nanopore microscope emerges as a promising tool to dynamically sense and characterize cellular products. The major advantage of this system is the precise positioning of the nanopore sensor in arbitrary locations across the cell membrane and even inside of the cell, thanks to AFM. Controlled localization of the nanopore chip into the cytoplasm and nucleus of the cell enables intracellular sensing, injection and mapping, including the ionic current map obtained from the nanoscale organization of a nuclear membrane for the first time in this study.

Scanning nanopore microscopy is expected to be important for fundamental biology and biophysics but it should also indirectly contribute to drug discovery. The precise positioning in combination with scanning not only generates functional images about the location of transporters and their activity but it also provides information about the heterogeneity of membranes. For example, the local density of ion-channels and pumps can be mapped on single cells, which has importance in neuroscience and many other cell biological subdisciplines.

Therefore, the approach will lead to better understanding of organization and function of secreting pathways on cell membranes, as well as providing a tool to study mechanical forces on translocating molecules.


Papers:

Localized detection of ions and biomolecules with
a force-controlled scanning nanopore microscope


A new tool for cell signalling research