Collagen structure: The molecular source of the tendon magic angle effect

Abstract

This review of tendon/collagen structure shows that the orientational variation in MRI signals from tendon, which is referred to as the "magic angle" (MA) effect, is caused by irreducible separation of charges on the main chain of the collagen molecule. These charges are held apart in a vacuum by stereotactic restriction of protein folding due in large part to a high concentration of hydroxyproline ring residues in the amino acids of mammalian collagen. The elevated protein electrostatic energy is reduced in water by the large dielectric constant of the highly polar solvent ( ϳ 80). The water molecules serve as dielectric molecules that are bound by an energy that is nearly equivalent to the electrostatic energy between the neighboring positive and negative charge pairs in a vacuum. These highly immobilized water molecules and secondary molecules in the hydrogenbonded water network are confined to the transverse plane of the tendon. Orientational restriction causes residual dipole coupling, which is directly responsible for the frequency and phase shifts observed in orientational MRI (OMRI) described by the MA effect. Reference to a wide range of biophysical measurements shows that native hydration is a monolayer on collagen h m ϭ 1.6 g/g, which divides into two components consisting of primary hydration on polar surfaces h pp ϭ 0.8 g/g and secondary hydration h s ϭ 0.8 g/g bridging over hydrophobic surface regions. Primary hydration further divides into side-chain hydration h psc ϭ 0.54 g/g and main-chain hydration h pmc ϭ 0.263 g/g. The main-chain fraction consists of water that bridges between charges on the main chain and is responsible for almost all of the enthalpy of melting ⌬H ϭ 70 J/g-dry mass. Main-chain water bridges consist of one extremely immobilized Ramachandran water bridge per tripeptide h Ra ϭ 0.0658 g/g and one double water bridge per tripeptide h dwb ϭ 0.1974 g/g, with three water molecules that are sufficiently slowed to act as the spinlattice relaxation sink for the entire tendon. THIS REVIEW OF BIOPHYSICAL STUDIES of mammalian tendon extends beyond the MR literature to show how the molecular structure of the collagen molecule causes the highly exceptional variation of MR signal with tendon orientation in the magnetic field that is referred to as the "magic angle" (MA) effect (1-14). Tendon is a unique tissue for elucidating not only orientational effects but also the molecular sources of MR contrast in other tissues. The unique "Rosetta stone" character of tendon relates to four structural factors:1. The nearly monomolecular composition of tendon, in which the collagen content approaches 100% of the total dry mass in some instances. 2. The uniform parallel alignment of collagen molecules along the tendon long axis, which provides tensile strength for connecting muscles to bones and forming cables necessary for mechanical motion of the body. 3. The quasi-crystalline association of collagen molecules in tendon, which allows the application of x-ray crystallography methods to both synthetic c...

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“…The average correlation time of cell water would be expected to decrease from 27 ps to several times slower than the correlation time of bulk water (1.74 ps). This degree of slowing is in the reported measured range for monolayer water coverage of tendon/collagen Rahal 2007 andCameron andFullerton 2008).…”

Micro‐CT dilatometry measures of molecular collagen hydration using bovine extensor tendon

“…As shown previously, 19 SHM theory predicts that each water molecule departing from a given water category causes equal changes in tendon properties but with different values for other water compartments. It is predicted that relative diameter d / d 0 , relative length l / l 0 , relative volume V / V 0 , and density will have segmental-linear properties.…”

“…The SHM makes predictions traceable to the molecular structure of the collagen molecule and was previously validated by DSC, 19 NMR, 20 MRI, 19 centrifugation dehydration, 21 and other methods as recently reviewed. 22 Initially, the SHM model hypothesized significant free energy differential between water fractions that allows depopulation of water compartments in sequence, but more recently, DSC studies have confirmed this point.…”

“…Briefly, the SHM molecular hydration model 19,22 relates protein water binding capacities to the alignment of water electric dipoles in electrostatic fields caused by irreducible spatial separation of positive amide and negative carbonyl groups on the protein backbone ͑see inset of Fig. 2͒.…”

On the anisotropy and inhomogeneity of permeability in articular cartilage

“…The interaction of water with collagen fibres (e.g., Fullerton and Rahal 2007) and other molecular chains (such as actin and microtubules) has been investigated extensively. Pollack (2001) reports that transport of water along filamentous structures is partly caused by the transport of solutes, which carry with them a "cloud" of structured water.…”