Regular Article - Living Systems

A mechanical test of the tenertaxis hypothesis for leukocyte diapedesis

¹ Department of Chemical and Biological Engineering, University of British Columbia, V6T 1Z3, Vancouver, BC, Canada
² Centre for Heart Lung Innovation, St Paul’s Hospital and University of British Columbia, V5Z 1M9, Vancouver, BC, Canada
³ Department of Mathematics, University of British Columbia, V6T 1Z2, Vancouver, BC, Canada

^d james.feng@ubc.ca

Received: 13 April 2021
Accepted: 21 June 2021
Published online: 8 July 2021

Abstract

As part of the immune response, leukocytes can directly transmigrate through the body of endothelial cells or through the gap between adjacent endothelial cells. These are known, respectively, as the transcellular and paracellular route of diapedesis. What determines the usage of one route over the other is unclear. A recently proposed tenertaxis hypothesis claims that leukocytes choose the path with less mechanical resistance against leukocyte protrusions. We examined this hypothesis using numerical simulation of the mechanical resistance during paracellular and transcellular protrusions. By using parameters based on human lung endothelium, our results show that the required force to breach the endothelium through the transcellular route is greater than paracellular route, in agreement with experiments. Moreover, experiments have demonstrated that manipulation of the relative strength between the two routes can make the transcellular route preferable. Our simulations have demonstrated this reversal and thus tentatively confirmed the hypothesis of tenertaxis.