Cellular chirality arising from the self-organization of the actin cytoskeleton

Yee Han Tee, Tom Shemesh, Visalatchi Thiagarajan, Rizal Fajar Hariadi, Karen L. Anderson, Christopher Page, Niels Volkmann, Dorit Hanein, Sivaraj Sivaramakrishnan, Michael M. Kozlov, Alexander D. Bershadsky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Cellular mechanisms underlying the development of left-right asymmetry in tissues and embryos remain obscure. Here, the development of a chiral pattern of actomyosin was revealed by studying actin cytoskeleton self-organization in cells with isotropic circular shape. A radially symmetrical system of actin bundles consisting of α-actinin-enriched radial fibres (RFs) and myosin-IIA-enriched transverse fibres (TFs) evolved spontaneously into the chiral system as a result of the unidirectional tilting of all RFs, which was accompanied by a tangential shift in the retrograde movement of TFs. We showed that myosin-IIA-dependent contractile stresses within TFs drive their movement along RFs, which grow centripetally in a formin-dependent fashion. The handedness of the chiral pattern was shown to be regulated by α-actinin-1. Computational modelling demonstrated that the dynamics of the RF-TF system can explain the pattern transition from radial to chiral. Thus, actin cytoskeleton self-organization provides built-in machinery that potentially allows cells to develop left-right asymmetry.

Original languageEnglish
Pages (from-to)445-457
Number of pages13
JournalNature Cell Biology
Volume17
Issue number4
DOIs
StatePublished - 30 Apr 2015

Funding

FundersFunder number
Joseph Klafter Chair in Biophysics956/10
Marie Curie network Virus Entry
National Institutes of HealthP01-GM066311
National Institute of General Medical SciencesP01GM098412
National University of Singapore
National Research Foundation Singapore
Ministry of Education - SingaporeR-714-006-006-271
Israel Science Foundation758/11

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