RT Journal Article SR Electronic T1 Contractility-induced self-organization of smooth muscle cells: from multilayer cell sheets to dynamic three-dimensional clusters JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.01.17.476602 DO 10.1101/2022.01.17.476602 A1 Xiuyu Wang A1 David Gonzalez-Rodriguez A1 Thomas Vourc’h A1 Pascal Silberzan A1 Abdul I. Barakat YR 2022 UL http://biorxiv.org/content/early/2022/01/20/2022.01.17.476602.abstract AB Smooth muscle cells (SMCs) are mural cells that play a vital contractile function in many tissues. Abnormalities in SMC organization are associated with many diseases including atherosclerosis, asthma, and uterine fibroids. Various studies have reported that SMCs cultured on flat surfaces can spontaneously form three-dimensional clusters whose organization resembles that encountered in some of these pathological settings. Remarkably, how these structures form remains unknown. Here we combine in vitro experiments and physical modeling to show that three-dimensional clusters initiate when cellular contractile forces induce a hole in a flat SMC sheet, a process that can be modeled as the brittle fracture of a viscoelastic material. The subsequent evolution of the nascent cluster can be modeled as an active dewetting process with cluster shape evolution driven by a balance between cluster surface tension, arising from both cell contractility and adhesion, and cluster viscous dissipation. The description of the physical mechanisms governing the spontaneous emergence of these intriguing three-dimensional clusters offers insight into SMC-related disorders.Competing Interest StatementThe authors have declared no competing interest.