Dynamics of endothelial intercellular junctions under ultrasonic cavitation and application in drug delivery

Opening the blood-brain barrier and ensuring the safe and effective passage of drugs across the intercellular junctions (IJs) are challenging problems in medicine. In this study, we establish a mathematical model of endothelial IJs and describe the dynamic response of intercellular junctions and their effect on the endothelial permeability under ultrasonic cavitation excitation. The calculations show that the linking points in IJs exhibit nonlinear strain behavior. The paracellular area and permeability governed by IJs are related to the amplitude, frequency and direction of the applied external force and its pulse duration. Importantly, the morphological observations of human umbilical vein endothelial cells provide preliminary support for the deformation behavior predicted by the mathematical model. This model can help us to understand the biomechanical response of endothelial junctional networks under external excitation and may provide a preliminary computational framework for screening parameters related to endothelial barrier modulation.