ArticleBiophysical journal2002
Three-dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues.
Article in Biophysical journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 291 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
291 citing papers in PubMed, 1 synthesis or guideline pooled it, 906 citations in OpenAlex.
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- Exploring liquid-liquid phase separation in vitro and in vivo using multimodal nonlinear optical imaging.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2025Article
- Cervical Collagen Network Porosity Assessed by SHG Endomicroscopy Distinguishes Preterm and Normal Pregnancy-A Pilot Study.IEEE transactions on bio-medical engineering · 2025Article
- A gene-encoded bioprotein second harmonic generation (SHG) probe from Autographa californica nuclear polyhedrosis virus (AcMNPV) polyhedrin for live cell imaging.European biophysics journal : EBJ · 2025Article
- Review
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- Mueller matrix analysis of a biologically sourced engineered tissue construct as polarimetric phantom.Journal of biomedical optics · 2024Article
- Review
231 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedCorrection.2012
- Erratum issued
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
We find that several key endogenous protein structures give rise to intense second-harmonic generation (SHG)-nonabsorptive frequency doubling of an excitation laser line. Second-harmonic imaging microscopy (SHIM) on a laser-scanning system proves, therefore, to be a powerful and unique tool for high-resolution, high-contrast, three-dimensional studies of live cell and tissue architecture. Unlike fluorescence, SHG suffers no inherent photobleaching or toxicity and does not require exogenous labels. Unlike polarization microscopy, SHIM provides intrinsic confocality and deep sectioning in complex tissues. In this study, we demonstrate the clarity of SHIM optical sectioning within unfixed, unstained thick specimens. SHIM and two-photon excited fluorescence (TPEF) were combined in a dual-mode nonlinear microscopy to elucidate the molecular sources of SHG in live cells and tissues. SHG arose not only from coiled-coil complexes within connective tissues and muscle thick filaments, but also from microtubule arrays within interphase and mitotic cells. Both polarization dependence and a local symmetry cancellation effect of SHG allowed the signal from species generating the second harmonic to be decoded, by ratiometric correlation with TPEF, to yield information on local structure below optical resolution. The physical origin of SHG within these tissues is addressed and is attributed to the laser interaction with dipolar protein structures that is enhanced by the intrinsic chirality of the protein helices.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.