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Review
. 2020 Jan 23;21(3):742.
doi: 10.3390/ijms21030742.

Computational Modeling of Claudin Structure and Function

Shadi Fuladi  1 , Ridaka-Wal Jannat  1 , Le Shen  2   3 , Christopher R Weber  2 , Fatemeh Khalili-Araghi  1
Affiliations
Review

Computational Modeling of Claudin Structure and Function

Shadi Fuladi et al. Int J Mol Sci. .

Abstract

Tight junctions form a barrier to control passive transport of ions and small molecules across epithelia and endothelia. In addition to forming a barrier, some of claudins control transport properties of tight junctions by forming charge- and size-selective ion channels. It has been suggested claudin monomers can form or incorporate into tight junction strands to form channels. Resolving the crystallographic structure of several claudins in recent years has provided an opportunity to examine structural basis of claudins in tight junctions. Computational and theoretical modeling relying on atomic description of the pore have contributed significantly to our understanding of claudin pores and paracellular transport. In this paper, we review recent computational and mathematical modeling of claudin barrier function. We focus on dynamic modeling of global epithelial barrier function as a function of claudin pores and molecular dynamics studies of claudins leading to a functional model of claudin channels.

Keywords: claudin; ion channel; ion transport; molecular dynamics; tight junction.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Mathematical modeling of tight junction permeability. (A) Electrodes were sealed over the intracellular space between MDCK I induced to express claudin-2 [12]. Each claudin-2 pore was defined by two closed states (C1, C2) and a single open state (O) according to the equation in [14] (B) In silico patch clamp recordings resembled in vitro tight junction patch clamp recordings from MDCK I monolayers expressing claudin-2 (recording from dataset of Weber et al. [12]). For the simulation, each green pore shown in panel A was modeled as 36 resistors per micron with defined opening and closing probabilities [14].
Figure 2
Figure 2
A refined model of claudin-15 paracellular channels [25]. Claudin-15 monomers assemble into double-row strands and form paracellular channels. (A) Top view of six claudin-15 monomers assembling into a double-row strand. (B) Snapshot of the simulation system showing claudin-15 monomers assembled between adjacent lipid bilayers. The pore regions are marked with circles. The water density across the simulation system and averaged over ∼250 ns of MD simulations, is shown: (C) parallel to the two membranes crossing the pores in the middle and (D) normal to the two membranes and crossing the pores in the middle. Figure is taken from [25] with slight modification.
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