Liquid-crystal organization of liver tissue

Abstract

Functional tissue architecture originates by self-assembly of distinct cell types, following tissue-specific rules of cell-cell interactions. In the liver, a structural model of the lobule was pioneered by Elias in 1949. This model, however, is in contrast with the apparent random 3D arrangement of hepatocytes. Since then, no significant progress has been made to derive the organizing principles of liver tissue. To solve this outstanding problem, we computationally reconstructed 3D tissue geometry from microscopy images of mouse liver tissue and analyzed it applying soft-condensed-matter-physics concepts. Surprisingly, analysis of the spatial organization of cell polarity revealed that hepatocytes are not randomly oriented but follow a long-range liquid-crystal order. This does not depend exclusively on hepatocytes receiving instructive signals by endothelial cells, since silencing Integrin-β1 disrupted both liquid-crystal order and organization of the sinusoidal network. Our results suggest that bi-directional communication between hepatocytes and sinusoids underlies the self-organization of liver tissue.

Integer topological defects organize stresses driving tissue morphogenesis

“…One usual marker of cell polarity is shape anisotropy( 1 ). Akin to elongated molecules in liquid crystals( 5 ), elongated cells can self-organize into patterns featuring long-range orientational order ( 6 – 9 ). Orientational fields often present topological defects, where the orientational order is ill-defined.…”

Resilience of three-dimensional sinusoidal networks in liver tissue

“…Here, we analyze network geometry using a digital reconstruction of the sinusoidal network based on high-resolution image data of adult mouse liver [13,14]. We develop a network generation algorithm that reproduces statistical features of the sinusoidal network (node degree distribution, edge length distribution, mean nematic order parameter), enabling us to simulate arbitrarily sized networks from spatially restricted biological samples and, moreover, to explore in silico a design space of three-dimensional networks.…”

“…Yet, topology suggests fundamental differences between two-dimensional and three-dimensional spatial networks, as it imposes constraints on the distribution of cycles in the network [12]. Here, we take advantage of recent technological advances in high-resolution imaging of adult mouse liver tissue [13,14], allowing us to study statistical geometry and resilience of three-dimensional sinusoidal networks.…”

Nature of active forces in tissues: how contractile cells can form extensile monolayers

“…For instance, recent studies demonstrated the importance of nematic organization of actin cytoskeleton in Hydra during morphogenesis, 52 while other studies have begun to explore the role of liquid-crystal ordering during morphogenesis 53 and in − vivo epithelial tissue patterning. 54 These findings highlight the importance of active nematic behaviours at a collective level to understand tissue shape and organization, factors central to morphogenesis. 52,53,[55][56][57][58] As such, the adaptation of cellular systems from extensile to contractile behaviours might be a crucial mechanism by which a collective living system undergoes morphological changes (sorting or tissue organiza- .…”