The interplay between matrix deformation and the coordination of turning events governs directed neutrophil migration in 3D matrices

Joshua François; Adithan Kandasamy; Yi-Ting Yeh; Amy Schwartz; Cindy Ayala; Ruedi Meili; Shu Chien; Juan C Lasheras; Juan C Del Álamo

doi:10.1126/sciadv.abf3882

The interplay between matrix deformation and the coordination of turning events governs directed neutrophil migration in 3D matrices

Sci Adv. 2021 Jul 14;7(29):eabf3882. doi: 10.1126/sciadv.abf3882. Print 2021 Jul.

Authors

Joshua François^{1

2

3}, Adithan Kandasamy^{4

5

6}, Yi-Ting Yeh^{4

2}, Amy Schwartz⁴, Cindy Ayala^{4

7

8}, Ruedi Meili⁴, Shu Chien², Juan C Lasheras^{4

2}, Juan C Del Álamo^{1

5

6}

Affiliations

¹ Department of Mechanical and Aerospace Engineering, University of California, San Diego, La Jolla, CA, USA. juancar@uw.edu joshua_francois@hms.harvard.edu.
² Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
³ Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
⁴ Department of Mechanical and Aerospace Engineering, University of California, San Diego, La Jolla, CA, USA.
⁵ Department of Mechanical Engineering, University of Washington, Seattle, WA, USA.
⁶ Center for Cardiovascular Biology, University of Washington, Seattle, WA, USA.
⁷ Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
⁸ Department of Bioengineering, University of California, San Francisco, San Francisco, CA, USA.

Abstract

Neutrophils migrating through extravascular spaces must negotiate narrow matrix pores without losing directional movement. We investigated how chemotaxing neutrophils probe matrices and adjust their migration to collagen concentration ([col]) changes by tracking 20,000 cell trajectories and quantifying cell-generated 3D matrix deformations. In low-[col] matrices, neutrophils exerted large deformations and followed straight trajectories. As [col] increased, matrix deformations decreased, and neutrophils turned often to circumvent rather than remodel matrix pores. Inhibiting protrusive or contractile forces shifted this transition to lower [col], implying that mechanics play a crucial role in defining migratory strategies. To balance frequent turning and directional bias, neutrophils used matrix obstacles as pivoting points to steer toward the chemoattractant. The Actin Related Protein 2/3 complex coordinated successive turns, thus controlling deviations from chemotactic paths. These results offer an improved understanding of the mechanisms and molecular regulators used by neutrophils during chemotaxis in restrictive 3D environments.

Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Grants and funding

R01 GM084227/GM/NIGMS NIH HHS/United States