Single-Molecular-Level Study of Claudin-1-Mediated Adhesion

• Published in: Langmuir Vol. 24; no. 2; pp. 490 - 495
• Main Authors: Lim, Tong Seng, Vedula, Sri Ram Krishna, Kausalya, P. Jaya, Hunziker, Walter, Lim, Chwee Teck
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 15.01.2008
• Subjects: Cell Adhesion - physiology; Chemistry; Claudin-1; Colloidal state and disperse state; Exact sciences and technology; General and physical chemistry; Kinetics; Membrane Proteins - physiology; Microscopy, Atomic Force; Monte Carlo Method; Surface physical chemistry; Dynamics; Force; Models; Solutes; Kinetics; Dissociation; Permeability; Diffusion; Adhesion; Mechanism; Protein
• ISSN: 0743-7463; 1520-5827
• DOI: 10.1021/la702436x

Claudins are proteins that are selectively expressed at tight junctions (TJs) of epithelial cells where they play a central role in regulating paracellular permeability of solutes across epithelia. However, the role of claudins in intercellular adhesion and the mechanism by which they regulate the diffusion of solutes are poorly understood. Here, using single molecule force spectroscopy, the kinetic properties and adhesion strength of homophilic claudin-1 interactions were probed at the single-molecule level. Within the range of tested loading rates (103−105 pN/s), our results showed that homophilic claudin-1 interactions have a reactive compliance of 0.363 ± 0.061 nm and an unstressed dissociation rate of 1.351 ± 1.312 s-1. This is more than 100-fold greater than that of E-cadherin. The weak and short-lived interactions between claudin-1 molecules make them highly unstable and dynamic in nature. Such a dynamic interaction is consistent with a model where breaking and resealing of TJ strands regulate the paracellular diffusion of solutes.