Elasticity in extracellular matrix 'shape modules' of tendon, cartilage, etc. A sliding proteoglycan-filament model

Abstract

Connective tissues (CTs), which define bodily shape, must respond quickly, robustly and reversibly to deformations caused by internal and external stresses. Fibrillar (elastin, collagen) elasticity under tension depends on molecular and supramolecular mechanisms. A second intra-/inter-molecular pair, involving proteoglycans (PGs), is proposed to cope with compressive stresses. PG interfibrillar bridges ('shape modules'), supramolecular structures ubiquitously distributed throughout CT extracellular matrices (ECMs), are examined for potential elastic properties. L-iduronate residues in shape module decoran PGs are suggested to be molecular springs, cycling through alternative conformations. On a larger scale, anionic glycosaminoglycan (AGAG) interfibrillar bridges in shape modules are postulated to take part in a sliding filament (dashpot-like) process, which converts local compressions into disseminated tensile strains. The elasticity of fibrils and AGAGs, manifest at molecular and larger-scale levels, provides a graduated and smooth response to stresses of varying degrees. NMR and rheo NMR, computer modelling, electron histochemical, biophysical and chemical morphological evidence for the proposals is reviewed.

Figure 1

A, the shape module. Antiparallel proteoglycan AGAG aggregates (shown as duplexes) link collagen fibrils (in section); (p), proteoglycan protein (Scott, 1992a). B, plan (left) and elevation of two-fold helices preferred (in solution) by shape module AGAGs (chondroitins, keratans) and HA (Scott, 1995) in which all glycosidic bonds are equatorial 1–3, 1–4 and hydrophobic patches (stippled) are identically placed, as are the waves and inter-residue H-bonds (dotted lines). Filled circles, N atoms. Hyaluronan (HA) is illustrated. C, side views of tertiary structures of AGAGs with twofold helical secondary structures as in B. Hydrophobic patches (cross-hatched) form hydrophobic bonds and acetamido-NH (▪, □) H-bonds to carboxylate (•, ○) on the adjacent AGAG. Filled symbols are below, and open symbols above, the plane of the diagram. The waves shown in B complement each other in these antiparallel aggregates. Arrows on the left indicate reducing end direction (Scott & Heatley, 1999). Lateral displacement of chain II with respect to chains I and III caused by movement apart of the shape module fibrils (A, above) is reversible, driven by the energy gain in reforming the broken hydrophobic and H-bonds.

Figure 2. Collagen fibril structure and PG-fibril interactions

Triple-helical tropocollagen packs spontaneously into a quarter-staggered array in the fibril, on the surface of which bands of polar and non-polar amino acids show up after e.g. UO₂²⁺ staining as a–e bar codes (BP, banding pattern). Each a-e repetition is a D period, in which four PG binding sites at the d, e (decoran) and a, c (KS PGs) bands are located (Scott, 1988).

Figure 3

A, Courtauld space-filling models of (a) GlcUA, (b) IdoUA C1, (c) IdoUA ²S_o and (d) IdoUA 1C, carboxylate at bottom. Red, oxygen; white, hydrogen. The DS longitudinal axis runs left-right through the equator of each. c) and d) are the more compact on this axis. B, elevation views of stick-and-ball models of twofold helical DS homopolymers comprising exclusively: top, ⁴C₁ IdoUA; middle, ¹C₄ IdoUA; bottom, ²S_o IdoUA. Carboxylate oxygens in red and sulphate ester sulphur in yellow. Drawn using Artist for QUANTA programme (cf. Scott et al. 1992). Compact IdoUAs confer shorter chain lengths (middle and bottom) for the same number of sugar units. Under tension these could elongate to longer (top) configurations.

Figure 4

Scheme of reversible deformation involving shape module AGAG reversible slippage (right), which converts local compression into delocalised tensile deformation (right). Collagen fibrils (vertical black) are bridged by shape modules, antiparallel AGAG chains (zigzags) covalently linked to PG protein (filled circles) which bind to fibrils at specific binding sites (see Fig. 2). The arrow (top left) indicates a functional crimp, which however cannot be equated with a known primary or secondary structure (see text). Orange horizontal lines indicate ECM into which the fibrils are anchored. Left half, ‘REST’ diagrams the positions of the AGAG chains, fibrils, etc. in an unstressed ECM. Right half, ‘COMPRESSED’ shows a compressive force (as a red probe pressing in the direction of the arrow) impacting on the ECM. The collagen fibril crimp yields under the impact and tissue H₂O is displaced into neighbouring spaces where it exerts pressure along the AGAG aggregates, causing slippage between the aggregate participants and unwinding of the fibril crimp. Open arrow, from right to left at bottom, indicates reversal of the slippage and crimp distortion to the resting state on removal of the compressive stress, contingent on the return to the original position of the tissue H₂O (see text). Not to scale.