Study on the role of microtubules on T cell migration under confined environments

Abstract

Purpose: Migration of T cells is critical for immune surveillance and immune responses. Microtubule is the largest cytoskeleton and it is highly related with cell migration, but the role of microtubule on T cell migration under confined environments, which is an emergent property of interstitial spaces in vivo for leukocyte migration, has not been studied. Methods: In this study, we first fabricated two different types of microchannels, wide microchannels (WMCs) that only confines T cells in vertical direction, and narrow microchannels (NMCs) that confines T cells in both vertical and horizontal directions. Then, morphology, velocity, and directional persistence of T cells in the different confined conditions were quantitatively analyzed. In addition, pharmacological inhibitors modulating microtubule stability were used to assess the roles of microtubule dynamics on T cell migration under confinement. Results: T cells within microchannels were tightly confined, exhibiting flattened or elongated morphologies depending on whether they were in WMCs or NMCs. Velocity and directional persistent of T cells increased as the degree of confinement increased. In addition, Taxol-treatment significantly reduced directional persistence of T cells under confined environments. Conclusions Dynamics of microtubule played an important role in the directional persistency of T cells in confined environments.