Enhanced substrate stress relaxation promotes filopodia-mediated cell migration

Kolade Adebowale; Ze Gong; Jay C Hou; Katrina M Wisdom; Damien Garbett; Hong-Pyo Lee; Sungmin Nam; Tobias Meyer; David J Odde; Vivek B Shenoy; Ovijit Chaudhuri

doi:10.1038/s41563-021-00981-w

Enhanced substrate stress relaxation promotes filopodia-mediated cell migration

Nat Mater. 2021 Sep;20(9):1290-1299. doi: 10.1038/s41563-021-00981-w. Epub 2021 Apr 19.

Authors

Kolade Adebowale^{1

2}, Ze Gong³, Jay C Hou⁴, Katrina M Wisdom^{5

6}, Damien Garbett⁷, Hong-Pyo Lee⁶, Sungmin Nam^{6

8

9}, Tobias Meyer^{7

10}, David J Odde⁴, Vivek B Shenoy^{3

5}, Ovijit Chaudhuri^{11

12}

Affiliations

¹ Department of Chemical Engineering, Stanford University, Stanford, CA, USA.
² Chemistry, Engineering, and Medicine for Human Health (ChEM-H), Stanford University, Stanford, CA, USA.
³ Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, PA, USA.
⁴ Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA.
⁵ Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
⁶ Department of Mechanical Engineering, Stanford University, Stanford, CA, USA.
⁷ Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA.
⁸ John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
⁹ Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
¹⁰ Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY, USA.
¹¹ Chemistry, Engineering, and Medicine for Human Health (ChEM-H), Stanford University, Stanford, CA, USA. chaudhuri@stanford.edu.
¹² Department of Mechanical Engineering, Stanford University, Stanford, CA, USA. chaudhuri@stanford.edu.

Abstract

Cell migration on two-dimensional substrates is typically characterized by lamellipodia at the leading edge, mature focal adhesions and spread morphologies. These observations result from adherent cell migration studies on stiff, elastic substrates, because most cells do not migrate on soft, elastic substrates. However, many biological tissues are soft and viscoelastic, exhibiting stress relaxation over time in response to a deformation. Here, we have systematically investigated the impact of substrate stress relaxation on cell migration on soft substrates. We observed that cells migrate minimally on substrates with an elastic modulus of 2 kPa that are elastic or exhibit slow stress relaxation, but migrate robustly on 2-kPa substrates that exhibit fast stress relaxation. Strikingly, migrating cells were not spread out and did not extend lamellipodial protrusions, but were instead rounded, with filopodia protrusions extending at the leading edge, and exhibited small nascent adhesions. Computational models of cell migration based on a motor-clutch framework predict the observed impact of substrate stress relaxation on cell migration and filopodia dynamics. Our findings establish substrate stress relaxation as a key requirement for robust cell migration on soft substrates and uncover a mode of two-dimensional cell migration marked by round morphologies, filopodia protrusions and weak adhesions.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Basement Membrane / metabolism
Biomechanical Phenomena
Cell Adhesion
Cell Line
Cell Line, Tumor
Cell Movement*
Elasticity
Humans
Pseudopodia / metabolism*

Abstract

Publication types

MeSH terms

Grants and funding