13C, 2H NMR studies of structural and dynamical modifications of glucose-exposed porcine aortic elastin

Silverstein M. C., Bilici K., Morgan S. W., Wang Y., Zhang Y., Boutis G. S.

Biophysical Journal, vol.108, no.7, pp.1758-1772, 2015 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 108 Issue: 7
  • Publication Date: 2015
  • Doi Number: 10.1016/j.bpj.2015.02.005
  • Journal Name: Biophysical Journal
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1758-1772
  • Istanbul Technical University Affiliated: No


Elastin, the principal component of the elastic fiber of the extracellular matrix, imparts to vertebrate tissues remarkable resilience and longevity. This work focuses on elucidating dynamical and structural modifications of porcine aortic elastin exposed to glucose by solid-state NMR spectroscopic and relaxation methodologies. Results from macroscopic stress-strain tests are also presented and indicate that glucose-treated elastin is mechanically stiffer than the same tissue without glucose treatment. These measurements show a large hysteresis in the stress-strain behavior of glucose-treated elastin-a well-known signature of viscoelasticity. Two-dimensional relaxation NMR methods were used to investigate the correlation time, distribution, and population of water in these samples. Differences are observed between the relative populations of water, whereas the measured correlation times of tumbling motion of water across the samples were similar. 13C magic-angle-spinning NMR methods were applied to investigate structural and dynamical modifications after glucose treatment. Although some overall structure is preserved, the process of glucose exposure results in more heterogeneous structures and slower mobility. The correlation times of tumbling motion of the 13C-1H internuclear vectors in the glucose-treated sample are larger than in untreated samples, pointing to their more rigid structure. The 13C cross-polarization spectra reveal a notably increased α-helical character in the alanine motifs after glucose exposure. Results from molecular dynamics simulations are provided that add further insight into dynamical and structural changes of a short repeat, [VPGVG]5, an alanine pentamer, desmosine, and isodesmosine sites with and without glucose. The simulations point to changes in the entropic and energetic contributions in the retractive forces of VPGVG and AAAAA motifs. The most notable change is the increase of the energetic contribution in the retractive force due to peptide-glucose interactions of the VPGVG motif, which may play an important role in the observed stiffening in glucose-treated elastin.