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The spatio-temporal organization of proteins within the cell membrane can govern various cellular functions, ultimately playing a role in disease progression. One interesting example is the human epidermal growth factor receptor 2 (HER2), a member of the epidermal growth factor receptor (EGFR) family. HER2 is known to be over-expressed in certain cancer types. In some sub-types of breast cancer, it is known that overexpressed HER2s are non-homogenously distributed on the cell membrane surface, forming HER2 clusters that consist of HER2s in close proximity to each other. One therapeutic strategy is to disrupt this clustering behavior. However, given the nanometer lengthscales involved, detecting these subtle changes has proven challenging. In this work, we propose and demonstrate a new fluorophore for imaging HER2 clustering behaviour based on the organic molecule Tetraphenylethylene (TPE). This molecule undergoes aggregation induced emission (AIE), a unique photophysical behaviour that results in an increase in fluorescent signal when the molecular motion of the TPE-containing molecule is restricted. By conjugating the fluorophore to a HER2 specific antibody, HER2 clustering disruption in HER2 over-expressing breast cancer cells in response to the introduction of an FDA-approved therapeutic is detected. While this antibody-conjugated fluorophore system is optimized for the detection of HER2, the imaging agent forms a modular platform that is adaptable by changing the targeting moeity. This imaging system will find applications in a wide range of membrane protein spatio-temporal investigations. |
