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

Research output: Contribution to journalArticlepeer-review

226 Scopus citations


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

Bibliographical note

Funding Information:
We thank P. Lappalainen for discussion, S. Hanks, B. M. Jockush, I. Kaverina, C. Otey, P. Roca-Cusachs, M. J. Schell and R. Wedlich-Soldner for providing reagents, C. Lu for writing the custom script for velocities measurement, Z. Z. Lieu for help in the knockdown study, S. Wolf for expert help in paper editing, the microscopy core facility at the Mechanobiology Institute for technical help and Sanford Burnham Medical Research Institute for electron microscopy work. This research has been supported by the National Research Foundation Singapore, Ministry of Education of Singapore, Grant R-714-006-006-271, and administrated by the National University of Singapore. K.L.A. and D.H. were supported by National Institutes of Health (NIH) grant P01-GM098412. C.P. and N.V. were supported by NIH grant P01-GM066311. M.M.K. was supported by the Israel Science Foundation (grant No.758/11) and the Marie Curie network Virus Entry, and holds the Joseph Klafter Chair in Biophysics. M.M.K. thanks the Mechanobiology Institute, National University of Singapore, for hospitality. A.D.B. holds the Joseph Moss Professorial Chair in Biomedical Research at the Weizmann Institute and is a Visiting Professor at the National University of Singapore and acknowledges support from the Israel Science Foundation (grant No. 956/10).

Publisher Copyright:
© 2015 Macmillan Publishers Limited.


Dive into the research topics of 'Cellular chirality arising from the self-organization of the actin cytoskeleton'. Together they form a unique fingerprint.

Cite this