Lens capsule as a model to study type IV collagen

Abstract

The study of collagen IV has benefited greatly from the seminal work conducted by Arthur Veis and colleagues over three decades ago. Through a series of electron microscopy studies focused on lens basement membrane, an appreciation was gained for the distinct network-forming properties of collagen IV. Veis correctly suggested that network assembly is a phenomenon of the non-collagenous termini of the molecule. This review seeks to document how the field advanced following these seminal conclusions, including recent discoveries regarding the molecular reinforcement of networks that support Veis' conclusions.

Figure 1. Schematic of collagen IV protomeric structure

(A) Domain structure of collagen IV protomer showing N-terminal 7S domain, triple helical collagenous domain, and C-terminal NC1 domain. (B) Adjoining protomers form a hexameric complex from constituent NC1 domains, which is covalently reinforced by sulfilimine cross-links.

Figure 2. LBM is distinguished among basement membranes by its low amount of sulfilimine cross-linking

(A) Schematic depicting the solubilization of NC1 domains from collagen IV matrices via collagenase treatment. (B) Non-reducing SDS-PAGE analysis of NC1 isolated from placenta and lens basement membrane. Upper protein bands represent NC1 dimers containing sulfilimine cross-links, while lower protein bands represent uncrosslinked NC1 domains. (C) Densitometic analysis of SDS-PAGE gels reveal LBM as being comprised of mostly monomeric NC1 domains, which contrasts with NC1 isolated from placental and glomerular basement membranes.