Mesothelial Lubrication and Pleural Homeostatsis

Beth Israel Deaconess Medical Center, Boston MA

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): The pleural, pericardial, and peritoneal cavities contain organs that must be able to change shape and size and to slide within their cavities to function normally. To facilitate the ability of the lungs, heart, and abdominal viscera to change shape and size and to move relative to the body wall, these cavities and their contents are well lubricated, allowing almost frictionless sliding of the organs in their container and on themselves. We propose to study the hydrodynamic mechanisms important for lubrication of mesothelial surfaces. Our hypothesis is that the sliding of wetted mesothelial surfaces against each other causes hydrodynamic pressures in the liquid that reduce maximal shear stresses and protect against cellular damage by preventing contact between delicate mesothelial cells, distributing the liquid more evenly, and regulating liquid volume. To the extent that our studies show whether or not mesothelial surfaces come into contact, our results will show to what extent either of the two contradictory views of pleural space geometry and mechanics applies in vivo. In Aim 1, we will use epi-fluorescence microscopy to explore evidence that sliding of wetted mesothelial surfaces causes reversible smoothing (deformation) and increases the uniformity of thickness of the liquid layer between the surfaces. In Aim 2, we will use rotational and linear sliding tribometers to measure shear force of sliding wetted mesothelial surfaces (i. e., tribological behavior) to determine the dependence of shear force on velocity, normal stress, history, and the nature of the lubricating fluid. In Aim 3, we will explore fluid dynamic mechanisms associated with the sliding of lungs during breathing that could circulate pleural liquid, redistribute liquid in the pleural space, and regulate liquid volume by controlling the efflux of pleural liquid via lymphatic channels. In Aim 4, we will visualize changes in mesothelial cell histology caused by shear stress using scanning electron microscopy. All aspects of the research will be supported by three-dimensional computational fluid dynamics and finite element models. Destruction of the mesothelium can lead to fibrosis and adhesions. To the extent that mesothelial lubrication preserves mesothelial integrity, it is vital to health. Our goal is to understand these normal physiological phenomena.