Quantification of cell edge velocities and traction forces reveals distinct motility modules during cell spreading

Benjamin J. Dubin-Thaler, Jake M. Hofman, Yunfei Cai, Harry Xenias, Ingrid Spielman, Anna V. Shneidman, Lawrence A. David, Hans Günther Döbereiner, Chris H. Wiggins, Michael Sheetz

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Actin-based cell motility and force generation are central to immune response, tissue development, and cancer metastasis, and understanding actin cytoskeleton regulation is a major goal of cell biologists. Cell spreading is a commonly used model system for motility experiments - spreading fibroblasts exhibit stereotypic, spatially-isotropic edge dynamics during a reproducible sequence of functional phases: 1) During early spreading, cells form initial contacts with the surface. 2) The middle spreading phase exhibits rapidly increasing attachment area. 3) Late spreading is characterized by periodic contractions and stable adhesions formation. While differences in cytoskeletal regulation between phases are known, a global analysis of the spatial and temporal coordination of motility and force generation is missing. Implementing improved algorithms for analyzing edge dynamics over the entire cell periphery, we observed that a single domain of homogeneous cytoskeletal dynamics dominated each of the three phases of spreading. These domains exhibited a unique combination of biophysical and biochemical parameters - a motility module. Biophysical characterization of the motility modules revealed that the early phase was dominated by periodic, rapid membrane blebbing; the middle phase exhibited continuous protrusion with very low traction force generation; and the late phase was characterized by global periodic contractions and high force generation. Biochemically, each motility module exhibited a different distribution of the actin-related protein VASP, while inhibition of actin polymerization revealed different dependencies on barbed-end polymerization. In addition, our whole-cell analysis revealed that many cells exhibited heterogeneous combinations of motility modules in neighboring regions of the cell edge. Together, these observations support a model of motility in which regions of the cell edge exhibit one of a limited number of motility modules that, together, determine the overall motility function. Our data and algorithms are publicly available to encourage further exploration.

Original languageEnglish (US)
Article numbere3735
JournalPloS one
Volume3
Issue number11
DOIs
StatePublished - Nov 17 2008
Externally publishedYes

Fingerprint

traction (mechanics)
Traction
Actins
Polymerization
cells
actin
Phase control
Fibroblasts
polymerization
Adhesion
Spatio-Temporal Analysis
Tissue
Membranes
Blister
microfilaments
Actin Cytoskeleton
cell movement
metastasis
biologists
Cell Movement

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Quantification of cell edge velocities and traction forces reveals distinct motility modules during cell spreading. / Dubin-Thaler, Benjamin J.; Hofman, Jake M.; Cai, Yunfei; Xenias, Harry; Spielman, Ingrid; Shneidman, Anna V.; David, Lawrence A.; Döbereiner, Hans Günther; Wiggins, Chris H.; Sheetz, Michael.

In: PloS one, Vol. 3, No. 11, e3735, 17.11.2008.

Research output: Contribution to journalArticle

Dubin-Thaler, BJ, Hofman, JM, Cai, Y, Xenias, H, Spielman, I, Shneidman, AV, David, LA, Döbereiner, HG, Wiggins, CH & Sheetz, M 2008, 'Quantification of cell edge velocities and traction forces reveals distinct motility modules during cell spreading', PloS one, vol. 3, no. 11, e3735. https://doi.org/10.1371/journal.pone.0003735
Dubin-Thaler, Benjamin J. ; Hofman, Jake M. ; Cai, Yunfei ; Xenias, Harry ; Spielman, Ingrid ; Shneidman, Anna V. ; David, Lawrence A. ; Döbereiner, Hans Günther ; Wiggins, Chris H. ; Sheetz, Michael. / Quantification of cell edge velocities and traction forces reveals distinct motility modules during cell spreading. In: PloS one. 2008 ; Vol. 3, No. 11.
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