Linking morphodynamics and directional persistence of T lymphocyte migration

Abstract

T cells play a central role in the adaptive immune response, and their directed migration is essential for homing to sites of antigen presentation. Like neutrophils, T lymphocytes are rapidly moving cells that exhibit amoeboid movement, characterized by a definitive polarity with F-actin concentrated at the front and myosin II elsewhere. In this study, we used total internal reflection fluorescence (TIRF) microscopy to monitor the cells' areas of contact with a surface presenting adhesive ICAM-1 and the chemokine, CXCL12/ SDF-1. Our analysis reveals that T-cell migration and reorientation are achieved by bifurcation and lateral separation of protrusions along the leading membrane edge, followed by cessation of one of the protrusions, which acts as a pivot for cell turning. We show that the distribution of bifurcation frequencies exhibits characteristics of a random, spontaneous process; yet, the waiting time between bifurcation events depends on whether or not the pivot point remains on the same side of the migration axis. Our analysis further suggests that switching of the dominant protrusion between the two sides of the migration axis is associated with persistent migration, whereas the opposite is true of cell turning. To help explain the bifurcation phenomenon and how distinct migration behaviours might arise, a spatio-temporal, stochastic model describing F-actin dynamics is offered.

Quantitative analysis of B-lymphocyte migration directed by CXCL13

“…B cells migrating on CXCL13 and ICAM-1 showed the characteristic amoeboid morphology and fast movement (average translocation speed ≈ 14 μm/min), consistent with previous studies (10, 12); however, the dilation/shrinking dynamics reported here is a new insight revealed using TIRF microscopy. This is distinct from the leading-edge dynamics reported for other fast-moving amoeboid cells, such as Dictyostelium discoideum and T lymphocytes (29, 36–38). Our analysis showed independent dilation/shrinking waves on the two sides of the cell front.…”

“…Our analysis showed independent dilation/shrinking waves on the two sides of the cell front. Our conclusion is that the balance between dilation/shrinking at the edges determines cell migration directionality, which stands in contrast to the bifurcation of protrusions that characterizes migration of primary T lymphocytes on CXCL12/ICAM-1 (29); the leading edge dynamics in B cells is more reminiscent of the instabilities associated with turning of fish keratocytes (39). …”

“…To compare the waiting time distribution to that of a Poisson process, comparison to an exponential distribution was performed as previously described (29). All fits were obtained using the curve fitting toolbox of MATLAB.…”

Crawling and turning in a minimal reaction-diffusion cell motility model: Coupling cell shape and biochemistry

“…In addition, Gorelik and Gautreau have recently suggested that arpin [63] may induce cells to turn by slowing them [12]; this is consistent with our result that slowing the cell (or decreasing the Peclet number) can cause turning. However, we emphasize that in other cell types turning is associated with different morphology and may not be controlled by the simple mechanism studied here [64]. …”

Protective effect of quercetin on acute lung injury in rats with sepsis and its influence on ICAM-1 and MIP-2 expression

“…It has been reported that ICAM-1 is an important adhesion molecule belonging to the immunoglobulin superfamily. ICAM-1 is involved in neutrophil chemotaxis by binding with the surface ligand CD11/CD18 on neutrophils and lymphocytes (Dominguez et al, 2015;Liu et al, 2015;Sumagin and Parkos, 2015). MIP-2 belongs to the chemokine C-X-C subfamily and induces marked chemotaxis in neutrophils and lymphocytes (Takahashi et al, 2009;Tateno et al, 2013;Vagima et al, 2015).…”