FULL PAPER 1801400 (1 of 7) © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.advopticalmat.de Bioinspired Amyloid Nanodots with Visible Fluorescence Nadezda Lapshina, Ivan I. Shishkin, Ramesh Nandi, Roman E. Noskov, Hani Barhom, Sijo Joseph, Boris Apter, Tal Ellenbogen, Amir Natan, Pavel Ginzburg, Nadav Amdursky, and Gil Rosenman* DOI: 10.1002/adom.201801400 mostly based on fluorescent (FL) agents of high brightness and combines exceptional optical properties with biocompatibility, biodegradability, and precise targeting both in vivo and in vitro. This includes inorganic semiconductor quantum dots, [2] carbon nanodots, [3] organic molecular dyes, [4] and genetically encoded universal FL proteins. [5] Additional specific class of extrinsic FL nanoprobes is amyloid- binding small molecule ligands (thioflavin T, Congo red and more) employed for tracking the kinetics of amyloid fibrils growth. [6] Each of the imaging agents has its inherent mechanism of photon emis- sion, which defines its figures of merit for bioimaging: FL spectral region, quantum yield (QY), and photobleaching. [7,8] For instance, quantum dots and organic dye molecules exhibit FL in the visible range and have very high QY exceeding 90%. However, the organic molecular dyes are limited for long-term bioimaging applica- tions because of photobleaching issues. The biocompatibility is another basic parameter of any biola- bels, which is especially critical for some organic dyes and inor- ganic semiconductor quantum dots, containing heavy metals. Recently found FL carbon nanodots are biocompatible but have a low QY. [9] The green fluorescence protein (GFP) and its homologues are the only molecules, known until today, having biological origin FL and providing unique biocompatibility. These proteins exhibit pronounced FL with QY reaching 90% covering the entire visible spectrum, which makes them unique FL tags [10] among unlimited number of nonfluorescent peptide and protein biomolecules. [1,2,5,7] Alternative composition-insensitive visible FL was recently found in biological and bioinspired nanostructures characterized by specific ordering of biomolecules into antiparallel β-sheets structures. This includes a wide variety of diverse biomolecular compositions, such as amyloidogenic proteins, [11,12] PEGylated peptides, [13,14] nonaromatic biogenic, and synthetic peptides [15] and recently natural silk fibrils. [16] The basic features of these FL nanostructures are similar fibrillar morphology, original β-sheets secondary structure, and identical visible FL optical spectrum. These common structural and optical prop- erties enable to relate all of them to a wide class of thermo- dynamically stable disease- and nondiseased-related amyloid structures. [17–19] Such β-sheet structures and visible FL can also Nanoscale bioimaging is a highly important scientific and technological tool, where fluorescent (FL) proteins, organic molecular dyes, inorganic quantum dots, and lately carbon dots are widely used as light emitting biolabels. In this work, a new class of visible FL bioorganic nanodots, self-assembled from short peptides of different composition and origin, is introduced. It is shown that the electronic energy spectrum of native nonfluorescent peptide nanodots (PNDs) is deeply modified upon thermally mediated refolding of their biological secondary structure from native metastable to stable β-sheet rich structure. This refolding leads to the appearance of a broadband optical absorption across visible region and tunable, excitation-dependent visible FL of the nanodots with a high quantum yield of ≈30%. It is shown that this intriguing biophotonic effect appears in several peptides/proteins and does not require the presence of aromatic residues. It is assumed that the origin of the phenomenon is related to proton transfer along network of reconstructed intermolecular hydrogen bonds, stabilizing the thermally induced supra- molecular β-sheet structure. The biocompatible FL PNDs can be potentially applied as high-resolution bioimaging labels toward advanced biotechnology and biomedical theranostics. N. Lapshina, Dr. I. I. Shishkin, Dr. R. E. Noskov, H. Barhom, Dr. S. Joseph, Prof. T. Ellenbogen, Dr. A. Natan, Dr. P. Ginzburg, Prof. G. Rosenman School of Electrical Engineering Faculty of Engineering Tel Aviv University Ramat Aviv Tel Aviv 6139001, Israel E-mail: gilr@eng.tau.ac.il R. Nandi, Prof. N. Amdursky Schulich Faculty of Chemistry Technion – Israel institute of Technology Technion City, Haifa 3200008, Israel Dr. B. Apter Faculty of Engineering Holon Institute of Technology 52 Golomb st., POB 305, Holon 5810201, Israel The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adom.201801400. Fluorescent Bioinspired Nanodots 1. Introduction Bioimaging is a principal method in biomedicine from local diagnosis and drug delivery to therapy and surgery. [1] It is Adv. Optical Mater. 2019, 7, 1801400