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Proceedings Paper

ISOCT study of collagen crosslinking of collagen in cancer models (Conference Presentation)
Author(s): Graham Spicer; Scott T. Young; Ji Yi; Lonnie D. Shea; Vadim Backman

Paper Abstract

The role of extracellular matrix modification and signaling in cancer progression is an increasingly recognized avenue for the progression of the disease. Previous study of field effect carcinogenesis with Inverse Spectroscopic Optical Coherence Tomography (ISOCT) has revealed pronounced changes in the nanoscale-sensitive mass fractal dimension D measured from field effect tissue when compared to healthy tissue. However, the origin of this difference in tissue ultrastructure in field effect carcinogenesis has remained poorly understood. Here, we present findings supporting the idea that enzymatic crosslinking of the extracellular matrix is an effect that presents at the earliest stages of carcinogenesis. We use a model of collagen gel with crosslinking induced by lysyl oxidase (LOXL4) to recapitulate the difference in D previously reported from healthy and cancerous tissue biopsies. Furthermore, STORM imaging of this collagen gel model verifies the morphologic effects of enzymatic crosslinking at length scales as small as 40 nm, close to the previously reported lower length scale sensitivity threshold of 35 nm for ISOCT. Analysis of the autocorrelation function from STORM images of collagen gels and subsequent fitting to the Whittle-Matérn correlation function shows a similar effect of LOXL4 on D from collagen measured with ISOCT and STORM. We extend this to mass spectrometric study of tissue to directly measure concentrations of collagen crosslink residues. The validation of ISOCT as a viable tool for non-invasive rapid quantification of collagen ultrastructure lends it to study other physiological phenomena involving ECM restructuring such as atherosclerotic plaque screening or cervical ripening during pregnancy.

Paper Details

Date Published: 27 April 2016
PDF: 1 pages
Proc. SPIE 9719, Biophysics, Biology, and Biophotonics: the Crossroads, 97190M (27 April 2016); doi: 10.1117/12.2212035
Show Author Affiliations
Graham Spicer, Northwestern Univ. (United States)
Scott T. Young, Northwestern Univ. (United States)
Ji Yi, Northwestern Univ. (United States)
Lonnie D. Shea, Univ. of Michigan (United States)
Vadim Backman, Northwestern Univ. (United States)


Published in SPIE Proceedings Vol. 9719:
Biophysics, Biology, and Biophotonics: the Crossroads
Adam Wax; Vadim Backman, Editor(s)

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