PROGRESS REPORT 1802579 (1 of 12) © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.advmat.de Biological Tissues as Active Nematic Liquid Crystals Thuan Beng Saw, Wang Xi, Benoit Ladoux,* and Chwee Teck Lim* DOI: 10.1002/adma.201802579 1. Introduction Nature’s basic building blocks frequently consist of aniso- tropic, rod-shaped molecules that can possess liquid crystalline Live tissues can self-organize and be described as active materials composed of cells that generate active stresses through continuous injection of energy. In vitro reconstituted molecular networks, as well as single-cell cytoskeletons show that their filamentous structures can portray nematic liquid crystalline properties and can promote nonequilibrium processes induced by active pro- cesses at the microscale. The appearance of collective patterns, the formation of topological singularities, and spontaneous phase transition within the cell cytoskeleton are emergent properties that drive cellular functions. More inte- grated systems such as tissues have cells that can be seen as coarse-grained active nematic particles and their interaction can dictate many important tissue processes such as epithelial cell extrusion and migration as observed in vitro and in vivo. Here, a brief introduction to the concept of active nematics is provided, and the main focus is on the use of this framework in the systematic study of predominantly 2D tissue architectures and dynamics in vitro. In addition how the nematic state is important in tissue behavior, such as epithelial expansion, tissue homeostasis, and the atherosclerosis disease state, is discussed. Finally, how the nematic organization of cells can be controlled in vitro for tissue engineering purposes is briefly discussed. Epithelial Liquid Crystals Dr. T. B. Saw, Prof. C. T. Lim Department of Biomedical Engineering National University of Singapore 4 Engineering Drive 3, Engineering Block 4, #04-08 Singapore 117583, Singapore E-mail: ctlim@nus.edu.sg Dr. W. Xi, Dr. B. Ladoux Institut Jacques Monod (IJM) CNRS UMR 7592 and Université Paris Diderot Paris, France E-mail: benoit.ladoux@univ-paris-diderot.fr Dr. B. Ladoux, Prof. C. T. Lim Mechanobiology Institute (MBI) National University of Singapore Singapore 117411, Singapore Prof. C. T. Lim Biomedical Institute for Global Health Research and Technology (BIGHEART) National University of Singapore MD6, 14 Medical Drive, #14-01 Singapore 117599, Singapore The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.201802579. properties, i.e., materials with molecules that can flow but have long-range orien- tational order, with interesting biological functions. For example, DNA or chromatin in the cell nucleus can form a cholesteric liquid crystal, i.e., a liquid crystalline phase with a twisting helical structure due to the intrinsic chirality of the molecules, that enhances genomic packing [1] and pos- sibly other genomic functions that require the efficient “scanning” of the DNA, such as DNA replication and repair. [2] Fur- thermore, the same helical organization of chitin, which is a matrix protein, can reduce the mechanical impact on cepha- lopods, while “layers” of helical cellulose strands in the beetle skin give rise to their iridescent colors based on Bragg-reflection principles. [3] Here, we want to focus not only on the ordered structures of tissues, but also on its interplay with active prop- erties that support tissue development and homeostasis through processes such as self-replication, renewal, selective destruc- tion, and sensing of the microenvironment. Starting from the molecular level, these processes require the cell cytoskeleton to actively react to environmental inputs, while having sufficient mechanical stability to sustain shape and function, and at the same time sufficient fluidity for remodeling. [4] Studies show that these cytoskeletal fibrous components possess essential attributes of a nematic liquid crystalline medium, [5–7] which is arguably the simplest liquid crystal phase. Briefly, the orientation field of the constituent rod-like parti- cles in a 3D nematic material is quantified by the nematic order parameter tensor, Q = 3S(nn - I/3)/2, where n, the director, is a unit vector dictating the local average orientation axis (Figure 1a), and S = 〈cos 2θ (m) 〉 is the scalar order parameter, where θ (m) is the angle between each nematic constituent with n. S = 1 means perfect alignment in the nematic phase, while S = 0 defines an isotropic phase. The domains of parallel orientation usually have a finite size characterized by the orientational correlation length. In 2D, there will be bends and splays in the material that distort the orientations (Figure 1b,c), which can be quantified by spatial gradients in the nematic order parameter, ∂ k Q ij . In inanimate physical systems, the defects can be induced by systemic fluctua- tions, external coupling fields such as electric fields, and boundary effects. [5] High bend and splay can lead to the local misalignment of the anisotropic particles and such singularities in the orienta- tion field are termed topological defects. [5,8,9] In theory, defects can form diverse patterns grouped into distinct classes based on the degree and direction of rotation of directors around the Adv. Mater. 2018, 1802579