The Effect of Composition and Inter- and Intrafibrillar Interactions on the Structure of Collagen IV Networks in the Computer-Simulated Glomerular Basement Membrane

The glomerular basement membrane of the kidney, responsible for performing ultrafiltration blood plasma, is largely comprised of type-IV collagen and laminin. Type-IV collagen self-assembles into a heterotrimer composed of three distinct domains (fig. 1A): (1) the globular non-collagenous NCl domain of ∼10 nm in diameter, (2) the non-collagenous 7S domain ∼30 nm in length and ∼3nm in diameter, and (3) the collagenous triple helix of ∼370 nm in length and ∼3 nm in diameter composed of a repeating Gly-X-Y subunit [1]. The heterotrimers associate with remarkable specificity from six genetically distinct α-chains, α₁(IV) to α₆(IV) forming α₁α₁α₂, α₃α₄α₅, and α₅α₅α₆ heterotrimers [2]. In the healthy glomerulus, α₁α₁α₂ ([α₁]₂α₂) is the predominate collagen while significant α₃α₄α₅ is present; α₅α₅α₆ exists only in negligible quantities [2].