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Rhobo6 is a cell-impermeable small-molecule fluorophore that displays reversible fluorogenic binding to glycans, making it a general, wash-free, and non-perturbative label for the extracellular matrix...

Paper on hydroxychloroquine led by French researcher Didier Raoult is second-most-cited study ever to be withdrawn.

Fluorescent probes for cell plasma membrane (PM) are generally based on amphiphilic anchors that incorporate non-covalently into biomembranes. Therefore, they are not compatible with fixation and permeabilization, presence of serum, or cell co-culture because of their exchange with the medium. Here, we report a concept of lipid-directed covalent labeling of PM, which exploits transient binding to lipid membrane surface generating high local dye concentration, thus favoring covalent ligation to random proximal membrane proteins. This concept yielded a class of fluorescent probes for PM (MemGraft), where a cyanine dye (Cy3 and Cy5) bears at its two ends low-affinity membrane anchor and reactive group: an activated ester or a maleimide. We found that MemGraft probes with these reactive groups provide efficient PM labelling, in contrast to a series of control compounds, including commercial Cy3-based labels of amino and thiol groups, revealing the crucial role of the membrane anchor combined with high reactivity of activated ester and a maleimide groups. In contrast to conventional PM probes, based on non-covalent interactions, MemGraft labelling approach is compatible with cell fixation, permeabilization, trypsinization and presence of serum. The latter allows long-term cell tracking and video imaging of cell PM dynamics without signs of phototoxicity. The covalent strategy also enables staining and long-term tracking of co-cultured cells labelled in different colors without probes exchange. Moreover, combination of different ratios of MemGraft-Cy3 and MemGraft-Cy5 probes enabled long-term cell barcoding in at least 5 color codes, important for tracking and visualizing multiple cells populations. Ultimately, we found that MemGraft strategy enables efficient biotinylation of cell surface, opening the path to cell surface engineering and cell manipulation. ### Competing Interest Statement The authors have declared no competing interest.

Interviews were conducted with 18 chemists from several subdisciplines of chemistry and include a diversity of demographics on the topic of creativity as seen through the eyes of Eureka moments. The experiences fell within three categories, i.e., (1) analytical problem-solving which can be reconstructed into a series of logical steps that can be identified; (2) memory retrieval processes of previously acquired knowledge; and (3) insights characterized by a sudden and unexpected understanding. There were variations of detail within each category. Suggestions for enhancing the probability of experiencing Eureka moments are provided.