Actin disassembly clock determines shape and speed of lamellipodial fragments

Noa Ofer, Alexander Mogilner, Kinneret Keren

Research output: Contribution to journalArticle

Abstract

A central challenge in motility research is to quantitatively understand how numerous molecular building blocks self-organize to achieve coherent shape and movement on cellular scales. A classic example of such self-organization is lamellipodial motility in which forward translocation is driven by a treadmilling actin network. Actin polymerization has been shown to be mechanically restrained by membrane tension in the lamellipodium. However, it remains unclear how membrane tension is determined, what is responsible for retraction and shaping of the rear boundary, and overall how actin-driven protrusion at the front is coordinated with retraction at the rear. To answer these questions, we utilize lamellipodial fragments from fish epithelial keratocytes which lack a cell body but retain the ability to crawl. The absence of the voluminous cell body in fragments simplifies the relation between lamellipodial geometry and cytoskeletal dynamics. We find that shape and speed are highly correlated over time within individual fragments, whereby faster crawling is accompanied by larger front-to-rear lamellipodial length. Furthermore, we find that the actin network density decays exponentially from front-to-rear indicating a constant net disassembly rate. These findings lead us to a simple hypothesis of a disassembly clock mechanism in which rear position is determined by where the actin network has disassembled enough for membrane tension to crush it and haul it forward. This model allows us to directly relate membrane tension with actin assembly and disassembly dynamics and elucidate the role of the cell membrane as a global mechanical regulator which coordinates protrusion and retraction.

Original languageEnglish (US)
Pages (from-to)20394-20399
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number51
DOIs
StatePublished - Dec 20 2011

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Actins
Membranes
Pseudopodia
Polymerization
Fishes
Cell Membrane
Research
Cell Body

Keywords

  • Cell motility
  • Keratocyte fragments

ASJC Scopus subject areas

  • General

Cite this

Actin disassembly clock determines shape and speed of lamellipodial fragments. / Ofer, Noa; Mogilner, Alexander; Keren, Kinneret.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 51, 20.12.2011, p. 20394-20399.

Research output: Contribution to journalArticle

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