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Sci Rep. 2017 Sep 14;7(1):11533. doi: 10.1038/s41598-017-11938-y.

Turning behaviors of T cells climbing up ramp-like structures are regulated by myosin light chain kinase activity and lamellipodia formation.

Author information

1
Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH) San 31, Hyoja-dong, Nam-Gu, Pohang, Gyeongbuk, 790-784, Korea.
2
Department of Bioengineering, University of Pennsylvania, 210 South 33rd Street, Philadelphia, PA, 19104, USA.
3
School of Interdisciplinary Bioscience and Bioengineering (I-Bio), Pohang University of Science and Technology (POSTECH) San 31, Hyoja-dong, Nam-Gu, Pohang, Gyeongbuk, 790-784, Korea.
4
Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH) San 31, Hyoja-dong, Nam-Gu, Pohang, Gyeongbuk, 790-784, Korea. jsdoh@postech.ac.kr.
5
School of Interdisciplinary Bioscience and Bioengineering (I-Bio), Pohang University of Science and Technology (POSTECH) San 31, Hyoja-dong, Nam-Gu, Pohang, Gyeongbuk, 790-784, Korea. jsdoh@postech.ac.kr.

Abstract

T cells navigate diverse microenvironments to perform immune responses. Micro-scale topographical structures within the tissues, which may inherently exist in normal tissues or may be formed by inflammation or injury, can influence T cell migration, but how T cell migration is affected by such topographical structures have not been investigated. In this study, we fabricated ramp-like structures with a 5 μm height and various slopes, and observed T cells climbing up the ramp-like structures. T cells encountering the ramp-like structures exhibited MLC accumulation near head-tail junctions contacting the ramp-like structures, and made turns to the direction perpendicular to the ramp-like structures. Pharmacological study revealed that lamellipodia formation mediated by arp2/3 and contractility regulated by myosin light chain kinase (MLCK) were responsible for the intriguing turning behavior of T cells climbing the ramp-like structures. Arp2/3 or MLCK inhibition substantially reduced probability of T cells climbing sharp-edged ramp-like structures, indicating intriguing turning behavior of T cells mediated by lamellipodia formation and MLCK activity may be important for T cells to access inflamed or injured tissues with abrupt topographical changes.

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