Epithelial Cell Chirality Revealed by Three-Dimensional Spontaneous Rotation

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 115; no. 48; pp. 12188 - 12193
• Main Authors: Chin, Amanda S., Worley, Kathryn E., Ray, Poulomi, Kaur, Gurleen, Fan, Jie, Wan, Leo Q.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 27-11-2018
• Subjects: Actin; Actinin; Animals; Asymmetry; Bioengineering; Biological Sciences; Biomaterials; Biomedical materials; Birth defects; Cell Culture Techniques; Cell Polarity; Cellular biology; Chirality; Congenital defects; Crosslinking; Dogs; Embryogenesis; Embryology; Embryonic growth stage; Environmental factors; Epithelial cells; Epithelial Cells - chemistry; Epithelial Cells - cytology; Extracellular matrix; Handedness; Imaging, Three-Dimensional; Madin Darby Canine Kidney Cells; Models, Biological; Morphogenesis; Physical Sciences; Polarity; Rotation; Spheroids; System effectiveness; left–right asymmetry; tissue morphogenesis; cell polarity; biomaterial; cell chirality
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1805932115

Our understanding of the left–right (LR) asymmetry of embryonic development, in particular the contribution of intrinsic handedness of the cell or cell chirality, is limited due to the confounding systematic and environmental factors during morphogenesis and a ack of physiologically relevant in vitro 3D platforms. Here we report an efficient two-layered biomaterial platform for determining the chirality of individual cells, cell aggregates, and self-organized hollow epithelial spheroids. This bioengineered niche provides a uniform defined axis allowing for cells to rotate spontaneously with a directional bias toward either clockwise or counterclockwise directions. Mechanistic studies reveal an actin-dependent, cell-intrinsic property of 3D chirality that can be mediated by actin cross-linking via α-actinin-1. Our findings suggest that the gradient of extracellular matrix is an important biophysicochemical cue influencing cell polarity and chirality. Engineered biomaterial systems can serve as an effective platform for studying developmental asymmetry and screening for environmental factors causing birth defects.