caa a22 4500 605480052 CHVBK 20210128100413.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s10544-015-9998-x doi (NATIONALLICENCE)springer-10.1007/s10544-015-9998-x Integrin associated proteins differentially regulate neutrophil polarity and directed migration in 2D and 3D [Elektronische Daten] [Yukie Yamahashi, Peter Cavnar, Laurel Hind, Erwin Berthier, David Bennin, David Beebe, Anna Huttenlocher] Directed neutrophil migration in blood vessels and tissues is critical for proper immune function; however, the mechanisms that regulate three-dimensional neutrophil chemotaxis remain unclear. It has been shown that integrins are dispensable for interstitial three-dimensional (3D) leukocyte migration; however, the role of integrin regulatory proteins during directed neutrophil migration is not known. Using a novel microfluidic gradient generator amenable to 2D and 3D analysis, we found that the integrin regulatory proteins Kindlin-3, RIAM, and talin-1 differentially regulate neutrophil polarization and directed migration to gradients of chemoattractant in 2D versus 3D. Both talin-1-deficient and RIAM-deficient neutrophil-like cells had impaired adhesion, polarization, and migration on 2D surfaces whereas in 3D the cells polarized but had impaired 3D chemotactic velocity. Kindlin-3 deficient cells were able to polarize and migrate on 2D surfaces but had impaired directionality. In a 3D environment, Kindlin-3 deficient cells displayed efficient chemotaxis. These findings demonstrate that the role of integrin regulatory proteins in cell polarity and directed migration can be different in 2D and 3D. Springer Science+Business Media New York, 2015 Neutrophil nationallicence Chemotaxis nationallicence Integrin regulatory proteins nationallicence Microfluidics nationallicence Yamahashi Yukie Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA aut Cavnar Peter Department of Biology, University of West Florida, Pensacola, FL, USA aut Hind Laurel Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, 1550 Linden Drive, Room 4205 MSB, 53706, Madison, WI, USA aut Berthier Erwin Department of Bioengineering, University of Wisconsin-Madison, Madison, WI, USA aut Bennin David Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA aut Beebe David Department of Bioengineering, University of Wisconsin-Madison, Madison, WI, USA aut Huttenlocher Anna Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA aut Biomedical Microdevices Springer US; http://www.springer-ny.com 17/5(2015-10-01), 1-9 1387-2176 17:5<1 2015 17 10544 https://doi.org/10.1007/s10544-015-9998-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10544-015-9998-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yamahashi Yukie Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA aut NATIONALLICENCE 700 1- Cavnar Peter Department of Biology, University of West Florida, Pensacola, FL, USA aut NATIONALLICENCE 700 1- Hind Laurel Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, 1550 Linden Drive, Room 4205 MSB, 53706, Madison, WI, USA aut NATIONALLICENCE 700 1- Berthier Erwin Department of Bioengineering, University of Wisconsin-Madison, Madison, WI, USA aut NATIONALLICENCE 700 1- Bennin David Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA aut NATIONALLICENCE 700 1- Beebe David Department of Bioengineering, University of Wisconsin-Madison, Madison, WI, USA aut NATIONALLICENCE 700 1- Huttenlocher Anna Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA aut NATIONALLICENCE 773 0- Biomedical Microdevices Springer US; http://www.springer-ny.com 17/5(2015-10-01), 1-9 1387-2176 17:5<1 2015 17 10544