Entrainment of Lymphatic Contraction to Oscillatory Flow

TL;DR

This study investigates how lymphangions, the contractile units of the lymphatic system, respond to oscillatory shear stress, revealing their shear sensitivity, entrainment behavior, and potential implications for lymphatic dysfunctions like lymphedema.

Contribution

It characterizes the response of lymphangions to dynamic shear stress and uncovers mechanisms of their entrainment and adaptation, advancing understanding of lymphatic mechanosensitivity.

Findings

Critical shear stress inhibits contraction significantly.

Entrainment depends on frequency difference and shear magnitude.

Lymphangion contractility adapts to oscillatory shear stress.

Abstract

Lymphedema, a disfiguring condition characterized by the asymmetrical swelling of the limbs, is suspected to be caused by dysfunctions in the lymphatic system. Lymphangions, the spontaneously contracting units of the lymphatic system, are sensitive to luminal wall shear stress. In this study, the response of the lymphangions to dynamically varying wall shear stress is characterized in isolated rat thoracic ducts in relation to their shear sensitivity. The critical shear stress above which the thoracic duct shows substantial inhibition of contraction was found to be significantly negatively correlated to the diameter of the lymphangion. The entrainment of the lymphangion to an applied oscillatory shear stress was found to be significantly dependent on the difference between the applied frequency and intrinsic frequency of contraction of the lymphangion. The strength of entrainment was also positively correlated to the applied shear stress when this shear was below the critical shear stress. The results suggest an adaptation of the lymphangion contractility to the existing oscillatory mechanical shear stress as a function of its intrinsic contractility and shear sensitivity. These adaptations might be crucial to ensure synchronized contraction of adjacent lymphangions through mechanosensitive means and might help explain the lymphatic dysfunctions that result from impaired mechanosensitivity.