Fluctuations of intracellular forces during cell protrusion

Lin Ji, James Lim, Gaudenz Danuser

Research output: Contribution to journalArticle

128 Scopus citations

Abstract

We present a model to estimate intracellular force variations from live-cell images of actin filament (F-actin) flow during protrusion-retraction cycles of epithelial cells in a wound healing response. To establish a mechanistic relationship between force development and cytoskelal dynamics, force fluctuations were correlated with fluctuations in F-actin turnover, flow and F-actin-vinculin coupling. Our analyses suggest that force transmission at focal adhesions requires binding of vinculin to F-actin and integrin (indirectly), which is modulated at the vinculin-integrin but not the vinculin-F-actin interface. Force transmission at focal adhesions is colocalized in space and synchronized in time with transient increases in the boundary force at the cell edge. Surprisingly, the maxima in adhesion and boundary forces lag behind maximal edge advancement by about 40 s. Maximal F-actin assembly was observed about 20 s after maximal edge advancement. On the basis of these findings, we propose that protrusion events are limited by membrane tension and that the characteristic duration of a protrusion cycle is determined by the efficiency in reinforcing F-actin assembly and adhesion formation as tension increases.

Original languageEnglish (US)
Pages (from-to)1393-1400
Number of pages8
JournalNature Cell Biology
Volume10
Issue number12
DOIs
StatePublished - Nov 14 2008

ASJC Scopus subject areas

  • Cell Biology

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