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Second harmonic generation (SHG) is a microscopic technique applicable to a broad spectrum of biological and medical imaging due to its excellent photostability, high signal-to-noise ratio (SNR) and narrow emission profile. Current SHG microscopy techniques rely on two main contrast modalities. These are endogenous SHG generated by tissue structures, which is clinically relevant but cannot be targeted to another location, or SHG nanoprobes, inorganic nanocrystals that can be directed to proteins and cells of interest, but cannot be applied for clinical imaging due to their chemical composition. Here we analyzed SHG signal generated by large-scale peptide assemblies. Our results show the sequence of peptides play an important role on both the morphology and SHG signal of the peptide assemblies. Changing peptide sequence allows confinement of large number of peptides to smaller voxels, generating intense SHG signal. With miniaturization of these peptides and their proper functionalization strategies, such bioinspired nanoparticles would emerge as valuable tools for clinical imaging.
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