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Sci Rep. 2017 Sep 22;7(1):12197. doi: 10.1038/s41598-017-12398-0.

Determination of extracellular matrix collagen fibril architectures and pathological remodeling by polarization dependent second harmonic microscopy.

Author information

1
CNRS, Institut de Physique de Rennes, Département Matière molle, UMR UR1-CNRS 6251, Université de Rennes1, F-35042, Rennes, France.
2
INSERM, Laboratoire Traitement du Signal et de l'Image, UMR UR1-INSERM U642, Université de Rennes1, F-35042, Rennes, France.
3
INSERM, UMR1085, IRSET Institut de Recherche sur la Santé l'Environnement et le Travail, SFR Biosit, Université de Rennes1, F-35043, Rennes, France.
4
CNRS, INSERM, Université de Nice Sophia Antipolis, iBV, Nice, 06100, France.
5
INSERM, UMR1085, IRSET Institut de Recherche sur la Santé l'Environnement et le Travail, SFR Biosit, Université de Rennes1, F-35043, Rennes, France. francois.tiaho@univ-rennes1.fr.

Abstract

Polarization dependence second harmonic generation (P-SHG) microscopy is gaining increase popularity for in situ quantification of fibrillar protein architectures. In this report, we combine P-SHG microscopy, new linear least square (LLS) fitting and modeling to determine and convert the complex second-order non-linear optical anisotropy parameter ρ of several collagen rich tissues into a simple geometric organization of collagen fibrils. Modeling integrates a priori knowledge of polyhelical organization of collagen molecule polymers forming fibrils and bundles of fibrils as well as Poisson photonic shot noise of the detection system. The results, which accurately predict the known sub-microscopic hierarchical organization of collagen fibrils in several tissues, suggest that they can be subdivided into three classes according to their microscopic and macroscopic hierarchical organization of collagen fibrils. They also show, for the first time to our knowledge, intrahepatic spatial discrimination between genuine fibrotic and non-fibrotic vessels. CCl4-treated livers are characterized by an increase in the percentage of fibrotic vessels and their remodeling involves peri-portal compaction and alignment of collagen fibrils that should contribute to portal hypertension. This integrated P-SHG image analysis method is a powerful tool that should open new avenue for the determination of pathophysiological and chemo-mechanical cues impacting collagen fibrils organization.

PMID:
28939903
PMCID:
PMC5610346
DOI:
10.1038/s41598-017-12398-0
[Indexed for MEDLINE]
Free PMC Article

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