study of the molecular and supramolecular organisation of elastic tissue by x-ray diffraction

2
Radiation Physics and Chemistry 71 (2004) 951–952 Study of the molecular and supramolecular organisation of elastic tissue by X-ray diffraction Layla Ali a , E.M. Green a , R.E. Ellis a , D.A. Bradley a , J.G. Grossmann b , C.P. Winlove a, * a Biomedical Physics Group, School of Physics, University of Exeter, Exeter EX4 4QL, UK b CCLRC, Daresbury Laboratory, Synchrotron Radiation Department, Daresbury, Warrington, WA4 4AD, UK 1. Introduction Elastin is the principal elastic protein in mammals. It constitutes up to 50% of the dry weight of tissues such as lung, blood vessels and ligaments where it is associated with a family of elastic microfibrillar glyco- proteins to form tissue-specific networks or fibres. Little is known about the internal organisation of these structures. Early reports (Serfani-Fracassini and Field, 1977) of regular organisation in dried fibres using X-ray diffraction or electron microscopy were often dismissed as artefactual, largely because such ordered structures were believed to be inconsistent with an entropic mechanism of elasticity. This view is now recognised to be erroneous and, as part of an analysis of the molecular bases of elasticity, we have begun to re- examine the organisation of elastin and its associated proteins. 2. Experimental methodology Equine nuchal ligament and porcine aorta obtained from the abattoir were studied, either intact, after alkali extraction (which produces pure elastin, but may cause a small amount of hydrolysis (Soskel et al., 1987)) or after GuHCl/collagenase extraction with or without DTE (preserving elastin structure and, in the latter case, the microfibrillar glycoproteins (Spina et al.,1999). Nuchal ligament fibres of dimension B4 cm 1 mm were dissected from the samples of ligament. Rings of aorta were of thickness B 2 mm and diameter B1 cm. Each of these samples was mounted on a purpose-made rig on either beamline 14.1 (wide-angle X-ray scattering, WAXS) or 2.1 (small-angle X-ray scattering, SAXS) at the SRS Daresbury, UK. The rig allowed the specimens to be equilibrated with water or primary alcohols and to be strained up to 100%. 3. Results and discussion The wide-angle diffraction patterns of relaxed nuchal elastin showed two broad diffraction rings correspond- ing to spacings of 0.45 and 0.93 nm that did not orient on stretching (Fig. 1). However at above 60% extension, the rings were not observed. Another sharp intense ring at spacing of 4.5 nm in which at small strains an equatorial reflection was produced, while at higher strain the ring was not visible. In addition, a diffuse equatorial peak with spacing extending between 5.5 and 8.0 nm appeared in relaxed and extended specimens. Clear meridional reflections at spacing of 9.1, 7.0, 5.8, 5.3 and 3.25 nm, became clearer with increasing strain in collagenase extracted fibres which could be due to the microfibrillar component in elastin. It appears that fibrillin does not affect the packing of elastin as the main diffraction pattern was preserved in both treatments of ligament fibres. The X-ray diffraction pattern of ligamentum elastin was partially reproduced in arterial elastin in particular the two broad diffraction peaks and the sharp intense ring appeared in identical position. In order to investigate the reversibility of the elastic properties of the tissue at a molecular level, samples ARTICLE IN PRESS *Corresponding author. Tel.: +44-1392-264140; fax: +44- 1392-264111. E-mail address: [email protected] (C.P. Winlove). 0969-806X/$ - see front matter r 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.radphyschem.2004.05.020

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Page 1: Study of the molecular and supramolecular organisation of elastic tissue by X-ray diffraction

Radiation Physics and Chemistry 71 (2004) 951–952

ARTICLE IN PRESS

*Correspond

1392-264111.

E-mail addr

0969-806X/$ - s

doi:10.1016/j.ra

Study of the molecular and supramolecular organisationof elastic tissue by X-ray diffraction

Layla Alia, E.M. Greena, R.E. Ellisa, D.A. Bradleya,J.G. Grossmannb, C.P. Winlovea,*

aBiomedical Physics Group, School of Physics, University of Exeter, Exeter EX4 4QL, UKbCCLRC, Daresbury Laboratory, Synchrotron Radiation Department, Daresbury, Warrington, WA4 4AD, UK

1. Introduction

Elastin is the principal elastic protein in mammals. It

constitutes up to 50% of the dry weight of tissues such

as lung, blood vessels and ligaments where it is

associated with a family of elastic microfibrillar glyco-

proteins to form tissue-specific networks or fibres. Little

is known about the internal organisation of these

structures. Early reports (Serfani-Fracassini and Field,

1977) of regular organisation in dried fibres using X-ray

diffraction or electron microscopy were often dismissed

as artefactual, largely because such ordered structures

were believed to be inconsistent with an entropic

mechanism of elasticity. This view is now recognised

to be erroneous and, as part of an analysis of the

molecular bases of elasticity, we have begun to re-

examine the organisation of elastin and its associated

proteins.

2. Experimental methodology

Equine nuchal ligament and porcine aorta obtained

from the abattoir were studied, either intact, after alkali

extraction (which produces pure elastin, but may cause a

small amount of hydrolysis (Soskel et al., 1987)) or after

GuHCl/collagenase extraction with or without DTE

(preserving elastin structure and, in the latter case, the

microfibrillar glycoproteins (Spina et al.,1999). Nuchal

ligament fibres of dimension B4 cm� 1mm were

ing author. Tel.: +44-1392-264140; fax: +44-

ess: [email protected] (C.P. Winlove).

ee front matter r 2004 Elsevier Ltd. All rights reserv

dphyschem.2004.05.020

dissected from the samples of ligament. Rings of aorta

were of thickness B 2mm and diameter B1 cm. Each of

these samples was mounted on a purpose-made rig on

either beamline 14.1 (wide-angle X-ray scattering,

WAXS) or 2.1 (small-angle X-ray scattering, SAXS) at

the SRS Daresbury, UK. The rig allowed the specimens

to be equilibrated with water or primary alcohols and to

be strained up to 100%.

3. Results and discussion

The wide-angle diffraction patterns of relaxed nuchal

elastin showed two broad diffraction rings correspond-

ing to spacings of 0.45 and 0.93 nm that did not orient

on stretching (Fig. 1). However at above 60% extension,

the rings were not observed. Another sharp intense ring

at spacing of 4.5 nm in which at small strains an

equatorial reflection was produced, while at higher

strain the ring was not visible. In addition, a diffuse

equatorial peak with spacing extending between 5.5 and

8.0 nm appeared in relaxed and extended specimens.

Clear meridional reflections at spacing of 9.1, 7.0, 5.8,

5.3 and 3.25 nm, became clearer with increasing strain in

collagenase extracted fibres which could be due to the

microfibrillar component in elastin. It appears that

fibrillin does not affect the packing of elastin as the main

diffraction pattern was preserved in both treatments of

ligament fibres. The X-ray diffraction pattern of

ligamentum elastin was partially reproduced in arterial

elastin in particular the two broad diffraction peaks and

the sharp intense ring appeared in identical position.

In order to investigate the reversibility of the elastic

properties of the tissue at a molecular level, samples

ed.

Page 2: Study of the molecular and supramolecular organisation of elastic tissue by X-ray diffraction

ARTICLE IN PRESS

Fig. 1. WAXS of unstretched elastin fibre.

Fig. 2. Background subtracted SAXS profiles of elastin fibres

obtained under different conditions.

L. Ali et al. / Radiation Physics and Chemistry 71 (2004) 951–952952

were returned to original length. Most of the features in

the pattern were preserved but the diffuse equatorial

peak and most meridionals were not immediately visible.

SAXS data showed an axial periodicity of approxi-

mately 65 nm where the third and fifth order of

diffraction were predominant and this pattern did not

change significantly as the samples stretched (Fig. 2).

The meridionals visualised in WAXS was found to be

the higher orders of the 65 nm spacing.

Replacing water by methanol or butanol, resulted in

loss of features in the diffraction pattern relating to

molecular level organisation and a significant increase of

about 0.5 nm in the spacing of the SAXS diffraction

peaks and changes of their intensities (Fig. 2).

Elastin is a highly hydrophobic protein in which

extensive b-structured hydrophobic domains are re-

peated by short, a-helical cross-linking segments. The

former are believed to be increasingly exposed to solvent

as the molecule is strained and hydrophobic effects are

thought to be important in determining elasticity. Our

results show, for the first time, the structural correlates

of this behaviour.

References

Serfani-Fracassini, A., Field, J.M., 1977. X-ray analysis of

enzymically purified elastin from bovine ligamentum

nuchae. Adv. Exp. Med. Biol. 79, 679–683.

Soskel, N.T., Wolt, T.B., Sandberg, L.B., 1987. Isolation and

characterisation of insoluble and soluble elastins. Methods

Enzymol. 144, 196–214.

Spina, M., Friso, A., Ewins, A.R., Parker, K.H., Winlove, C.P.,

1999. Physicochemical properties of arterial elastin and its

associated glycoproteins. Biopolymers 49, 255–265.