Why Are There Two Types of Collagen IV in Glomerular Basement Membrane?

Basement membrane provides, amongst other functions, the mechanical support for tissues in higher organisms. The microstructure of this membrane arises from the self-assembly of its the various components, most notably collagen IV. While virtually all basement membranes contain the α1α1α2 collagen IV protomer, the more interrupted α3α4α5 collagen IV protomer only appears in the specialized basement membranes of organs such as the kidney. We will present Monte Carlo simulation data that suggest a structural role for the α3α4α5 protomers in these more specialized systems, focusing on glomerular filtration in the kidney. In the context of a minimal model of collagen IV, we considered two possible roles for the increased cross-linking in the α3α4α5 protomers: (i) intraprotomeric disulfide bonds increase the protomer stiffness and (ii) interprotomeric disulfide bonding stabilizes lateral interactions. Case (i) tended to produce networks consisting of a large number of small pores, indicating a low membrane permeability. In contrast, we found that case (ii) produces highly connected networks featuring a number of large pores, leading to a high membrane permeability. Importantly, the latter network structures are only achieved when the mole fraction of α3α4α5 protomers in the network reaches physiological levels. As a result, we postulate that the α3α4α5 protomers in the kidney basement membrane impart the requisite combination of mechanical strength and permeability required for glomerular filtration.