Wall shear stress influences adhesion and extravasation of Borrelia burgdorferi in a 3D tissue-engineered microvascular model

Lyme disease is a tick-borne disease primarily caused by the bacterium Borrelia burgdorferi ( Bb ). Following a tick bite, Bb is injected into the dermis and colonizes the local tissue, where it can spread to distant organs through the vascular system. Although dissemination is a crucial factor in disease progression, our understanding of the mechanisms and factors that affect Bb dissemination through circulation is incomplete. To assess the role of wall shear stress (WSS) on Bb adhesion and extravasation, we perfused a 3D tissue-engineered microvessel with fluorescently labeled Bb at different wall shear stresses. The rate of Bb adhesion and extravasation from the microvessel was strongly dependent on WSS. Bb adhered to the endothelium in an elongated morphology and occasionally exhibited “flipping” events with one end of the Bb anchored and the other end detaching and reattaching downstream. Finally, circulating Bb did not induce endothelial activation following 6 h of perfusion, although increased microvessel permeability at low WSS was correlated with increased Bb adhesion events. Our results provide a new approach to investigating Bb dissemination and offers new insights into the mechanisms of Bb extravasation.