@article{liu_asokan_bear_haugh_2016, title={Quantitative analysis of B-lymphocyte migration directed by CXCL13}, volume={8}, ISSN={["1757-9708"]}, DOI={10.1039/c6ib00128a}, abstractNote={B-lymphocyte migration, directed by chemokine gradients, is essential for homing to sites of antigen presentation. B cells move rapidly, exhibiting amoeboid morphology like other leukocytes, yet quantitative studies addressing B-cell migration are currently lacking relative to neutrophils, macrophages, and T cells. Here, we used total internal reflection fluorescence (TIRF) microscopy to characterize the changes in shape (morphodynamics) of primary, murine B cells as they migrated on surfaces with adsorbed chemokine, CXCL13, and the adhesive ligand, ICAM-1. B cells exhibited frequent, spontaneous dilation and shrinking events at the sides of the leading membrane edge, a phenomenon that was predictive of turning versus directional persistence. To characterize directed B-cell migration, a microfluidic device was implemented to generate gradients of adsorbed CXCL13 gradients. Haptotaxis assays revealed a modest yet consistently positive bias of the cell's persistent random walk behavior towards CXCL13 gradients. Quantification of tactic fidelity showed that bias is optimized by steeper gradients without excessive midpoint density of adsorbed chemokine. Under these conditions, B-cell migration is more persistent when the direction of migration is better aligned with the gradient.}, number={8}, journal={INTEGRATIVE BIOLOGY}, publisher={Royal Society of Chemistry (RSC)}, author={Liu, Xiaji and Asokan, Sreeja B. and Bear, James E. and Haugh, Jason M.}, year={2016}, pages={894–903} }
 @article{liu_welf_haugh_2015, title={Linking morphodynamics and directional persistence of T lymphocyte migration}, volume={12}, ISSN={["1742-5662"]}, DOI={10.1098/rsif.2014.1412}, abstractNote={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.}, number={106}, journal={JOURNAL OF THE ROYAL SOCIETY INTERFACE}, author={Liu, Xiaji and Welf, Erik S. and Haugh, Jason M.}, year={2015}, month={May} }
 @article{vernekar_wallace_wu_chao_shannon k. o'connor_raleigh_liu_haugh_reichert_2014, title={Bi-ligand surfaces with oriented and patterned protein for real-time tracking of cell migration}, volume={123}, ISSN={["1873-4367"]}, DOI={10.1016/j.colsurfb.2014.09.020}, abstractNote={A bioactive platform for the quantitative observation of cell migration is presented by (1) presenting migration factors in a well-defined manner on 2-D substrates, and (2) enabling continuous cell tracking. Well-defined substrate presentation is achieved by correctly orienting immobilized proteins (chemokines and cell adhesion molecules), such that the active site is accessible to cell surface receptors. A thiol-terminated self-assembled monolayer on a silica slide was used as a base substrate for subsequent chemistry. The thiol-terminated surface was converted to an immobilized metal ion surface using a maleimido-nitrilotriacetic acid (NTA) cross-linker that bound Histidine-tagged recombinant proteins on the surface with uniform distribution and specific orientation. This platform was used to study the influence of surface-immobilized chemokine SDF-1α and cell adhesion molecule ICAM-1 on murine splenic B lymphocyte migration. While soluble SDF-1α induced trans-migration in a Boyden Chamber type chemotaxis assay, immobilized SDF-1α alone did not elicit significant surface-migration on our test-platform surface. Surface-immobilized cell adhesion protein, ICAM-1, in conjunction with activation enabled migration of this cell type on our surface. Controlled exposure to UV light was used to produce stable linear gradients of His-tagged recombinant SDF-1α co-immobilized with ICAM-1 following our surface chemistry approach. XPS and antibody staining showed defined gradients of outwardly oriented SDF-1α active sites. This test platform can be especially valuable for investigators interested in studying the influence of surface-immobilized factors on cell behavior and may also be used as a cell migration enabling platform for testing the effects of various diffusible agents.}, journal={COLLOIDS AND SURFACES B-BIOINTERFACES}, publisher={Elsevier BV}, author={Vernekar, Varadraj N. and Wallace, Charles S. and Wu, Mina and Chao, Joshua T. and Shannon K. O'Connor and Raleigh, Aimee and Liu, Xiaji and Haugh, Jason M. and Reichert, William M.}, year={2014}, month={Nov}, pages={225–235} }