title: Cellular chirality arising from the self-organization of the actin cytoskeleton.
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.
authors: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
authors: Yee Han
authors: YH
authors: Tee
authors: Faculty of Biology, Technion - Israel Institute of Technology, Haifa 32000, Israel.
authors: Tom
authors: T
authors: Shemesh
authors: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
authors: Visalatchi
authors: V
authors: Thiagarajan
authors: Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors: Rizal Fajar
authors: RF
authors: Hariadi
authors: Bioinformatics and Systems Biology Program, Sanford Burnham Medical Research Institute, La Jolla, California 92037, USA.
authors: Karen L
authors: KL
authors: Anderson
authors: Bioinformatics and Systems Biology Program, Sanford Burnham Medical Research Institute, La Jolla, California 92037, USA.
authors: Christopher
authors: C
authors: Page
authors: Bioinformatics and Systems Biology Program, Sanford Burnham Medical Research Institute, La Jolla, California 92037, USA.
authors: Niels
authors: N
authors: Volkmann
authors: Bioinformatics and Systems Biology Program, Sanford Burnham Medical Research Institute, La Jolla, California 92037, USA.
authors: Dorit
authors: D
authors: Hanein
authors: Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors: Sivaraj
authors: S
authors: Sivaramakrishnan
authors: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Michael M
authors: MM
authors: Kozlov
authors: 1] Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore [2] Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: Alexander D
authors: AD
authors: Bershadsky
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology*; D000185:Actinin / Q000378:metabolism; D000205:Actomyosin / Q000502:physiology*; D002460:Cell Line; D048430:Cell Shape / Q000502:physiology*; D003198:Computer Simulation; D006801:Humans; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: C528567:Actn1 protein, mouse; D034741:RNA, Small Interfering; D000185:Actinin; D000205:Actomyosin; D024507:Nonmuscle Myosin Type IIA