Actomyosin meshwork mechanosensing enables tissue shape to orient cell force

Abstract

Sculpting organism shape requires that cells produce forces with proper directionality. Thus, it is critical to understand how cells orient the cytoskeleton to produce forces that deform tissues. During Drosophila gastrulation, actomyosin contraction in ventral cells generates a long, narrow epithelial furrow, termed the ventral furrow, in which actomyosin fibres and tension are directed along the length of the furrow. Using a combination of genetic and mechanical perturbations that alter tissue shape, we demonstrate that geometrical and mechanical constraints act as cues to orient the cytoskeleton and tension during ventral furrow formation. We developed an in silico model of two-dimensional actomyosin meshwork contraction, demonstrating that actomyosin meshworks exhibit an inherent force orienting mechanism in response to mechanical constraints. Together, our in vivo and in silico data provide a framework for understanding how cells orient force generation, establishing a role for geometrical and mechanical patterning of force production in tissues.

Hypothesis: Caco‐2 cell rotational 3D mechanogenomic turing patterns have clinical implications to colon crypts

“…Therefore, it is feasible to combine these techniques to assess tight junction geometric patterns potentially useful to monitor the transformation of normal to abnormal (e.g. cancer) actomyosin meshwork pattern(s) . Human colon epithelium demonstrates various patterns during colonoscopy that correlate with different physiological and pathological conditions, which can be recognized using recently developed artificial intelligence algorithms .…”

“…cancer) actomyosin meshwork pattern(s). 3,28,29 Human colon epithelium demonstrates various patterns during colonoscopy that correlate with different physiological and pathological conditions, which can be recognized using recently developed artificial intelligence algorithms. 16,29 2D/3D patterns consistent with Turing's hypothesis appear to be present in our clinical data set (Figure 2A).…”

Curling of epithelial monolayers reveals coupling between active bending and tissue tension

“…This indicates that the coupling exists without any change of the tissue spontaneous curvature, which could occur in response to signaling. Such mechanical coupling could have implications in vivo as it was shown recently that disruption of in-plane tension anisotropy in the Drosophila embryo can prevent mesoderm invagination driven by apical constriction (30), while compression generated by cell migration is required to correctly shape the optic cup alongside basal recruitment of Myosin II in zebrafish (31). Since in-plane stresses can be transferred through long-range mechanical interactions (32,33), our measurements further emphasize a potential role for tissue-scale force generation in the shaping of epithelia.…”

Downregulation of basal myosin‐ II is required for cell shape changes and tissue invagination

“…Epithelial invagination is a key morphogenetic process that contributes to the positioning of germ layers during gastrulation and shaping of organs during later stages of embryogenesis (Schock & Perrimon, 2002;Martin & Goldstein, 2014;Pearl et al, 2017). Over the course of the last two decades, the internalization of mesodermal cells during Drosophila melanogaster gastrulation, which is usually referred to as ventral furrow formation, has emerged as a powerful system to dissect the mechanisms controlling tissue invagination (Kolsch et al, 2007;Martin et al, 2009;Mason et al, 2013;Chanet et al, 2017). Both experimental and theoretical work point toward a key role of apical constriction in generating the initial forces necessary to drive invagination (Conte et al, 2009;He et al, 2014;Guglielmi et al, 2015).…”