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Biological processes are dynamic by nature, and cells are constantly changing to respond to changes in their environment. Whether it is immune cells that respond to an invading bacteria or intestine cells that absorb nutrients from the gut. There is great value in closely inspecting fixed cells, which were quite literally frozen in time, preserving great detail on their intricate structures. Alongside that, much can also be learned from examining live cells, which can still respond to the ever-changing environment.
Assays like FRET or single-particle tracking are great for studying dynamic processes in cells, including drug discovery assays. G Protein Coupled-Receptors (GPCR) are a family of cell surface receptors that transform cues from the environment into cellular signaling. Many of these receptors are also involved in disease processes, from hypertension through diabetes, asthma and cancer to neurodegenerative conditions. The primary mechanism behind the activity of these receptors is the association and dissociation of different subunits, leading to different signaling outcomes inside the cells. External interventions, namely small organic molecules, peptides or even antibodies, can bind these receptors outside the cell and modify their activity. Therefore, it is not surprising that many efforts are invested to target GPCRs. FRET can be used to monitor the activity of these experimental drugs in cell cultures: Simply label two subunits of the receptor, apply the drug and measure their association and dissociation to gain accurate, quantitative information on the extent of the drug activity. Naturally, this type of assay can only be done if the cells are alive and able to respond to environmental cues.
Live-cell imaging is also very useful when answering questions about dynamics in cell biology. One example of this is the accumulation of repair proteins around DNA breaks: using fluorescently-labeled proteins, it is possible to record these events as they happen and gain invaluable information about minuscule molecular events. Equally, single-particle tracking of membrane proteins can shed light not only on the active trafficking of proteins to the membrane, but also on the biophysical characteristics of the cell membrane itself. Importantly, these methods are not exclusive to mammalian cells, and they can just as well be applied to unicellular organisms, viruses, and even isolated vesicles.
Naturally, live-cell imaging has to account for the optimal conditions cells need to thrive. The standard room temperature is far from ideal for cells: dynamic processes are slowed down and sometimes even modified or halted. It is immensely valuable to have an incubator to keep cells where they can be directly imaged. Cells can then grow in their optimal conditions with only a minimal interruption to their normal activity. With the right equipment, time-lapse single-molecule imaging is no longer a hypothetical option.
We recently teamed up with Tokai Hit, the leading manufacturer of stage-top incubators, to design a special incubator just for our Nanoimager. We are very excited to offer the opportunity to keep the cells healthy and warm while obtaining top-quality super-resolution imaging. We are thrilled to push the boundaries of super-resolution a little further, with optimal imaging options for scientists as well as for their samples!
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Kusumi, A., Tsunoyama, T. & Hirosawa, K. et al. Tracking single molecules at work in living cells. Nat. Chem. Biol. 10, 524–532 (2014).
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