Corneal collagen fibril structure in three dimensions: Structural insights into fibril assembly, mechanical properties, and tissue organization

David Holmes1, Christopher J. Gilpin1, Clair Baldock1, Ulrike Ziese1, Abraham J. Koster1, Karl E. Kadler1
1Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, Stopford Building 2.205, Oxford Road, Manchester M13 9PT, United Kingdom; and Department of Molecular Cell Biology, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands

Tóm tắt

The ability of the cornea to transmit light while being mechanically resilient is directly attributable to the formation of an extracellular matrix containing orthogonal sheets of collagen fibrils. The detailed structure of the fibrils and how this structure underpins the mechanical properties and organization of the cornea is understood poorly. In this study, we used automated electron tomography to study the three-dimensional organization of molecules in corneal collagen fibrils. The reconstructions show that the collagen molecules in the 36-nm diameter collagen fibrils are organized into microfibrils (≈4-nm diameter) that are tilted by ≈15° to the fibril long axis in a right-handed helix. An unexpected finding was that the microfibrils exhibit a constant-tilt angle independent of radial position within the fibril. This feature suggests that microfibrils in concentric layers are not always parallel to each other and cannot retain the same neighbors between layers. Analysis of the lateral structure shows that the microfibrils exhibit regions of order and disorder within the 67-nm axial repeat of collagen fibrils. Furthermore, the microfibrils are ordered at three specific regions of the axial repeat of collagen fibrils that correspond to the N- and C-telopeptides and the d-band of the gap zone. The reconstructions also show macromolecules binding to the fibril surface at sites that correspond precisely to where the microfibrils are most orderly.

Từ khóa


Tài liệu tham khảo

10.1006/jsbi.1998.3991

10.1016/0022-2836(84)90424-8

10.1038/282878a0

10.1016/0022-2836(87)90631-0

10.1016/0141-8130(81)90018-0

10.1038/219157a0

10.1016/0022-2836(78)90419-9

10.1007/BF01114803

10.1006/jmbi.1997.1449

10.1083/jcb.106.3.999

10.1042/bj3160001

10.1006/dbio.1999.9383

10.1016/S0021-9258(18)47783-6

10.1083/jcb.121.5.1181

10.1016/S0968-4328(00)00043-3

10.1016/S0021-9258(19)77922-8

10.1083/jcb.106.3.991

Holden P. Meadows R. S. Chapman K. L. Grant M. E. Kadler K. E. & Briggs M. D. (2001) J. Biol. Chem. in press.

Thur J. Rosenberg K. Nitsche D. P. Pihlajamaa T. Ala-Kokko L. Heinegard D. Paulsson M. & Maurer P. (2001) J. Biol. Chem. in press.

10.1073/pnas.84.17.6040

10.1002/(SICI)1097-0177(199605)206:1<49::AID-AJA5>3.0.CO;2-0

10.1096/fasebj.10.5.8621059

10.1074/jbc.274.27.18843

10.1006/exer.1999.0789

10.1083/jcb.141.5.1277

10.1038/75664

10.1006/jmbi.1999.3384

10.1006/jsbi.1996.0013

10.1016/0889-1605(86)90018-2

10.1016/0022-2836(82)90317-5

10.1016/0892-0354(90)90018-N

10.1016/0141-8130(89)90009-3

10.1111/j.1432-1033.1994.00943.x

10.1074/jbc.270.32.18865

10.1016/0005-2795(70)90303-X

10.1002/bip.360211115

10.1074/jbc.273.25.15598

10.1042/bj2520313

S Chakravarti, M Petroll, J Hassell, J Jester, J H Lass, J Paul, D E Birk Invest Ophthalmol Visual Sci 41, 3365–3373 (2000).

10.1074/jbc.C000278200

Y Lan, C Cummings, J K Sheehan, K E Kadler, D F Holmes, J A Chapman Dermatan Sulphate Proteoglycans. Chemistry, Biology, Chemical Pathology, ed J E Scott (Portland Press, London), pp. 183–192 (1993).

10.1159/000055616

10.1016/0892-0354(90)90018-N