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Most of the studies on this topic have been carried out on epithelial cells plated on micropatterned substrates, where cell motion is confined in regions of well-defined shapes coated with extracellular matrix adhesive proteins. The driver of collective rotation in such conditions has not been clearly elucidated, although it has been speculated that spatial confinement can play an essential role in triggering cell rotation. Here, we study the growth of epithelial cell colonies freely expanding (i.e. with no physical constraints) on the surface of cell culture plates and focus on collective cell rotation in such conditions, a case which has received scarce attention in the literature. One of the main findings of our work is that coordinated cell rotation spontaneously occurs in cell clusters in the free growth regime, thus implying that cell confinement is not necessary to elicit collective rotation as previously suggested. The extent of collective rotation was size and shape dependent: a highly coordinated disc-like rotation was found in small cell clusters with a round shape, while collective rotation was suppressed in large irregular cell clusters generated by merging of different clusters in the course of their growth. The angular motion was persistent in the same direction, although clockwise and anticlockwise rotations were equally likely to occur among different cell clusters. Radial cell velocity was quite low as compared to the angular velocity, in agreement with the free expansion regime where cluster growth is essentially governed by cell proliferation. A clear difference in morphology was observed between cells at the periphery and the ones in the core of the clusters, the former being more elongated and spread out as compared to the latter. Overall, our results, to our knowledge, provide the first quantitative and systematic evidence that coordinated cell rotation does not require a spatial confinement and occurs spontaneously in freely expanding epithelial cell colonies, possibly as a mechanism for the system.<\/jats:p>","DOI":"10.1098\/rsif.2022.0719","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T08:12:24Z","timestamp":1677053544000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Collective rotational motion of freely expanding T84 epithelial cell colonies"],"prefix":"10.1098","volume":"20","author":[{"given":"Flora","family":"Ascione","sequence":"first","affiliation":[{"name":"Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale (DICMAPI), Universit\u00e0 di Napoli Federico II, P.le Tecchio 80, 80125 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Caserta","sequence":"additional","affiliation":[{"name":"Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale (DICMAPI), Universit\u00e0 di Napoli Federico II, P.le Tecchio 80, 80125 Napoli, Italy"},{"name":"CEINGE Biotecnologie Avanzate, Via Sergio Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Speranza","family":"Esposito","sequence":"additional","affiliation":[{"name":"Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale (DICMAPI), Universit\u00e0 di Napoli Federico II, P.le Tecchio 80, 80125 Napoli, Italy"},{"name":"European Institute for Research in Cystic Fibrosis, San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria Rachela","family":"Villella","sequence":"additional","affiliation":[{"name":"Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale (DICMAPI), Universit\u00e0 di Napoli Federico II, P.le Tecchio 80, 80125 Napoli, Italy"},{"name":"European Institute for Research in Cystic Fibrosis, San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Maiuri","sequence":"additional","affiliation":[{"name":"European Institute for Research in Cystic Fibrosis, San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4670-9141","authenticated-orcid":true,"given":"Mehrana R.","family":"Nejad","sequence":"additional","affiliation":[{"name":"The Rudolf Peierls Centre for Theoretical Physics, Department of Physics, University of Oxford, Parks Road, Oxford OX1 3PU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amin","family":"Doostmohammadi","sequence":"additional","affiliation":[{"name":"The Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8268-5469","authenticated-orcid":true,"given":"Julia M.","family":"Yeomans","sequence":"additional","affiliation":[{"name":"The Rudolf Peierls Centre for Theoretical Physics, Department of Physics, University of Oxford, Parks Road, Oxford OX1 3PU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Guido","sequence":"additional","affiliation":[{"name":"Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale (DICMAPI), Universit\u00e0 di Napoli Federico II, P.le Tecchio 80, 80125 Napoli, Italy"},{"name":"CEINGE Biotecnologie Avanzate, Via Sergio Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2023,2,22]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2012.149"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1204291110"},{"key":"e_1_3_6_4_2","first-page":"4557","article-title":"Migration of coordinated cell clusters in mesenchymal and epithelial cancer explants in vitro","volume":"55","author":"Friedl P","year":"1995","unstructured":"Friedl P, Noble PB, Walton PA, Laird DW, Chauvin PJ, Tabah RJ, Black M, Z\u00e4nker KS. 1995 Migration of coordinated cell clusters in mesenchymal and epithelial cancer explants in vitro. 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