Mechanical tension induces lateral movement of intramembrane components of the tight junction: studies on mouse mammary cells in culture.

Abstract

Occluding junctions of mammary epithelial cells in nonproliferating primary culture occasionally display an atypical pattern of intramembrane strands oriented predominantly perpendicular, instead of roughly parallel, to the apical border of the junction. To test whether the orienting influence was a centripetal cytoskeletal tension often observed in epithelial sheets on fixed substrates, we seeded cells at low density; this allows them to spread maximally while forming a barely confluent pavement. The result was a fourfold increase in the percentage of junctions with the strongly aligned, atypical pattern. Closely similar configurations were observed as the earliest detectable effect of chelation of extracellular Ca ++, which induced pronounced centripetal contraction of the cell body. Externally imposed tension, applied so as to stretch cells in one direction only, affected the positions of strands in stretched junctions as might be predicted, by flattening their undulations, increasing their alignment parallel to the apical border. Thus mechanical tension alone, whether inherent in the cytoskeleton or imposed on the cell surface by exogenous force, can cause coordinate lateral displacement of macromolecular assemblies within the membranes of both joined cells.

Equibiaxial deformation-induced injury of alveolar epithelial cells in vitro

“…The outcome measure of the study presented here, breakdown of cell membrane integrity, is at the extreme end of this continuum. More subtle changes in barrier properties may include increased leakiness of the tight junctions connecting alveolar epithelial cells (38,50) or changes in active transport across the alveolar epithelial barrier (46). Reversible structural and functional changes in blood-gas barrier integrity have been reported during some in situ and in vivo lung inflation studies (17,21).…”

Loosening tight junctions. Lessons from the intestine.

“…This suggestion was certainly plausible since it had been shown that mechanically applied lateral tension (39), which presumably would be the result if rings contracted, was capable of altering ZO structure. Using cytochalasin D, an agent that affects actin microfilaments, we were able to demonstrate that intestinal absorptive cell ZOs became perturbed in structure and that ZO charge selectivity and resistance became markedly diminished (9).…”

AMP-activated Protein Kinase (AMPK) Activation and Glycogen Synthase Kinase-3β (GSK-3β) Inhibition Induce Ca2+-independent Deposition of Tight Junction Components at the Plasma Membrane

“…These cell junctions regulate the paracellular diffusion of small molecules and restrain the movement of proteins between the apical and the basolateral membrane compartments (1). A number of studies have demonstrated that extracellular Ca 2ϩ is essential for both the development of new junctions (2-4) and the stabilization of mature junctions (5)(6)(7)(8)(9)(10).…”