Directed Cell Migration: Integration of Signaling Adhesion, and Cytoskeletal Dynamics
We and other multicellular organisms are evolved with the amazing ability to heal. Similar to the way our bodies respond to infection, wound healing involves the recruitment of specific cells between tissues, i.e., directed cell migration. Another, more insidious example of the same basic process is the exodus of cancer cells from primary tumors. The migration of a select subpopulation of invasive cancer cells results in the colonization of secondary tumors (metastasis), leading many to characterize cancer as a ‘cell migration disease’.
Research in the Haugh laboratory has focused primarily on migration of fibroblasts, which is directed by both chemical and physical cues during wound healing. Especially recently, we have also studied cancer cell and lymphocyte (T and B cell) migration. Our approach in this area of research centers on live-cell microscopy, interrogating dynamics of signaling, adhesion, and cytoskeletal processes; when warranted, the analysis of these measurements is integrated with computational methods and biophysical models. Publications selected from this line of research are listed below.
Related Publications
Mohan K, Nosbisch JL, Elston TC, Bear JE, Haugh JM (2017). A reaction-diffusion model explains amplification of the PLC/PKC pathway in fibroblast chemotaxis. Biophysical Journal, 113 185-194.
Johnson HE, Haugh JM (2016). Are filopodia privileged signaling structures in migrating cells? Biophysical Journal, 111: 1827-1830.
Liu X, Asokan SB, Bear JE, Haugh JM (2016). Quantitative analysis of B-lymphocyte migration directed by CXCL13. Integrative Biology, 8: 894-903.
King SJ, Asokan SB, Haynes EM, Zimmerman SP, Rotty JD, Alb JG Jr, Tagliatela A, Blake DR, Lebedeva IP, Marston D, Johnson HE, Parsons M, Sharpless NE, Kuhlman B, Haugh JM, Bear JE (2016). Lamellipodia are crucial for haptotactic sensing and response. Journal of Cell Science, 129: 2329-2342.
Haynes EM, Asokan SB, King SJ, Johnson HE, Haugh JM, Bear JE (2015). “GMFβ controls branched actin content and lamellipodial retraction in fibroblasts.” Journal of Cell Biology, 209: 803-812.
Liu X, Welf ES, Haugh JM (2015). Linking morphodynamics and directional persistence of T lymphocyte migration. Journal of the Royal Society Interface, 12: pii:20141412.
Johnson HE, King SJ, Asokan SB, Rotty JD, Bear JE, Haugh JM (2015). F-actin bundles direct the initiation and orientation of lamellipodia through adhesion-based signaling. Journal of Cell Biology, 208: 443-455. Featured in the biosights podcast series and JCB journal club.
Rotty JD, Wu C, Haynes EM, Winkelman JD, Suarez C, Johnson HE, Haugh JM, Kovar DR, Bear JE (2015). Profilin-1 serves as a gatekeeper for actin assembly by Arp2/3-dependent and -independent pathways. Developmental Cell, 32: 54-67.
Asokan SB, Johnson HE, Rahman A, King SJ, Rotty JD, Lebedeva I, Haugh JM, Bear JE (2014). Mesenchymal chemotaxis requires selective inactivation of Myosin II at the leading edge via a non-canonical PLCγ/PKCα pathway. Developmental Cell, 31: 747-760.
Vernekar VN, Wallace CS, Wu M, Chao JT, O’Connor S, Raleigh A, Liu X, Haugh JM, Reichert WM (2014). Bi-ligand surfaces with oriented and patterned protein for real-time tracking of cell migration. Colloids and Surfaces B: Biointerfaces, 123: 225-235.
Bear JE, Haugh JM (2014). Directed migration of mesenchymal cells: where signaling and the cytoskeleton meet. Current Opinion in Cell Biology, 30C: 74-82.
Johnson HE, Haugh JM (2013). Quantitative analysis of phosphoinositide 3-kinase (PI3K) signaling using live-cell total internal reflection fluorescence (TIRF) microscopy. Current Protocols in Cell Biology, 61: 14.14.1-24 (Methods Article).
Welf ES, Johnson HE, Haugh JM (2013). Bidirectional coupling between integrin-mediated signaling and actomyosin mechanics explains matrix-dependent intermittency of leading-edge motility. Molecular Biology of the Cell, 24: 3945-3955.
Ott LE, Sung EJ, Melvin AT, Sheats MK, Haugh JM, Adler KB, Jones SL (2013). Fibroblast migration is regulated by Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS) protein. PLOS ONE, 8: e66512.
Haugh JM (2012). Live-cell fluorescence microscopy with molecular biosensors: What are we really measuring? Biophysical Journal, 102: 2003-2011 (featured article). Featured in the Biophysical Journal best of 2012 issue.
Welf ES, Ahmed S, Johnson, HE, Melvin AT, Haugh JM (2012). Migrating fibroblasts reorient directionality by a metastable, PI3K-dependent mechanism. Journal of Cell Biology, 197: 105-114. Featured in the biosights podcast series and JCB journal club.
Welf ES, Haugh JM (2012). Stochastic models of cell protrusion arising from spatiotemporal signaling and adhesion dynamics. Methods in Cell Biology, 110: 223-241 (Methods article).
Melvin AT, Welf ES, Wang Y, Irvine DJ, Haugh JM (2011). In chemotaxing fibroblasts, both high-fidelity and weakly biased cell movements track the localization of PI3K signaling. Biophysical Journal, 100: 1893-1901 (featured article).
Ahmed S, Yang H, Ozcam AE, Efimenko K, Weiger MC, Genzer J, Haugh JM (2011). Poly(vinylmethylsiloxane) elastomer networks as functional materials for cell adhesion and migration studies. Biomacromolecules, 12: 1265-1271.
Welf ES, Haugh JM (2011). Signaling pathways that control cell migration: models and analysis. Wiley Interdisciplinary Reviews Systems Biology & Medicine, 3: 231-240 (Focused Review).
Cirit M, Krajcovic M, Choi CK, Welf ES, Horwitz AF, Haugh JM (2010). Stochastic model of integrin-mediated signaling and adhesion dynamics at the leading edges of migrating cells. PLOS Computational Biology, 6: e1000688.
Welf ES, Haugh JM (2010). Stochastic dynamics of membrane protrusion mediated by the DOCK180/Rac pathway in migrating cells. Cellular and Molecular Bioengineering, 3: 30-39.
Weiger MC, Ahmed S, Welf ES, Haugh JM (2010). Directional persistence of cell migration coincides with stability of asymmetric intracellular signaling. Biophysical Journal, 98: 67-75 (featured article).
Weiger MC, Wang C-C, Krajcovic M, Melvin AT, Rhoden JJ, Haugh JM (2009). Spontaneous phosphoinositide 3-kinase signaling dynamics drive spreading and random migration of fibroblasts. Journal of Cell Science, 122: 313-323.
Monine MI, Haugh JM (2008). Cell population-based model of dermal wound invasion with heterogeneous intracellular signaling properties. Cell Adhesion & Migration, 2: 137-145. (Simulation codes and instructions).
Schneider IC, Haugh JM (2006). Mechanisms of gradient sensing and chemotaxis: conserved pathways, diverse regulation. Cell Cycle, 5: 1130-1134 (Extra View).
Haugh JM, Schneider IC (2006). Effectiveness factor for spatial gradient sensing in living cells. Chemical Engineering Science, 61: 5603-5611.
Haugh JM (2006). Deterministic model of dermal wound invasion incorporating receptor-mediated signal transduction and spatial gradient sensing. Biophysical Journal, 90: 2297-2308.
Schneider IC, Haugh JM (2005). Quantitative elucidation of a distinct spatial gradient-sensing mechanism in fibroblasts. Journal of Cell Biology, 171: 883-892. )
Schneider IC, Parrish EM, Haugh JM (2005). Spatial analysis of 3′ phosphoinositide signaling in living fibroblasts, III: Influence of cell morphology and morphological polarity. Biophysical Journal, 89: 1420-1430.
Schneider IC, Haugh JM (2004). Spatial analysis of 3′ phosphoinositide signaling in living fibroblasts: II. Parameter estimates for individual cells from experiments. Biophysical Journal, 86: 599-608.
Haugh JM, Schneider IC (2004). Spatial analysis of 3′ phosphoinositide signaling in living fibroblasts: I. Uniform stimulation model and bounds on dimensionless groups. Biophysical Journal, 86: 589-598.
Haugh JM, Codazzi F, Teruel M, Meyer T (2000). Spatial sensing in fibroblasts mediated by 3′ phosphoinositides. Journal of Cell Biology, 151: 1269-1279.