altered actin centripetal retrograde flow in physically restricted immunological synapses肌动蛋白改变心逆行流动物理限制免疫突触.pdfVIP

Altered Actin Centripetal Retrograde Flow in Physically Restricted Immunological Synapses Cheng-han Yu1,2, Hung-Jen Wu2,3, Yoshihisa Kaizuka4,5, Ronald D. Vale4,6, Jay T. Groves1,2,3,6* 1 Research Centre of Excellence in Mechanobiology, National University of Singapore, Singapore, Singapore, 2 Department of Chemistry, University of California, Berkeley, California, United States of America, 3 Physical Biosciences and Materials Sciences Divisions, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America, 4 Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, California, United States of America, 5 Biomaterials Center, National Institute for Materials Science, Tsukuba, Ibaraki, Japan, 6 Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America Abstract Antigen recognition by T cells involves large scale spatial reorganization of numerous receptor, adhesion, and costimulatory proteins within the T cell-antigen presenting cell (APC) junction. The resulting patterns can be distinctive, and are collectively known as the immunological synapse. Dynamical assembly of cytoskeletal network is believed to play an important role in driving these assembly processes. In one experimental strategy, the APC is replaced with a synthetic supported membrane. An advantage of this configuration is that solid structures patterned onto the underlying substrate can guide immunological synapse assembly into altered patterns. Here, we use mobile anti-CD3e on the spatial-partitioned supported bilayer to ligate and trigger T cell receptor (TCR) in live Jurkat T cells. Simultaneous tracking of both TCR clusters and GFP-actin speckles reveals their dynamic association and individual flow patterns. Actin retrograde flow directs the inw