title: 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.
authors.affiliation: Department of Chemical and Biomolecular Engineering, North Carolina State University, Campus Box 7905, Raleigh, NC 27695, USA.
authors.forename: Xiaji
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Chemical and Biomolecular Engineering, North Carolina State University, Campus Box 7905, Raleigh, NC 27695, USA.
authors.forename: Erik S
authors.initials: ES
authors.lastname: Welf
authors.affiliation: Department of Chemical and Biomolecular Engineering, North Carolina State University, Campus Box 7905, Raleigh, NC 27695, USA jason_haugh@ncsu.edu.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Haugh
mesh_terms: D000199:Actins / Q000502:physiology*; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology; D048429:Cell Size; D002478:Cells, Cultured; D003198:Computer Simulation; D006801:Humans; D008560:Membrane Fluidity / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D015233:Models, Statistical; D020409:Molecular Motor Proteins / Q000502:physiology*; D013269:Stochastic Processes; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*
chemical_list: D000199:Actins; D020409:Molecular Motor Proteins
keywords: TIRF microscopy; cell migration; chemokine; image analysis