Self-Organizing Actomyosin Patterns on the Cell Cortex at Epithelial Cell-Cell Junctions

Abstract

The behavior of actomyosin critically determines morphologically distinct patterns of contractility found at the interface between adherent cells. One such pattern is found at the apical region (zonula adherens) of cell-cell junctions in epithelia, where clusters of the adhesion molecule E-cadherin concentrate in a static pattern. Meanwhile, E-cadherin clusters throughout lateral cell-cell contacts display dynamic movements in the plane of the junctions. To gain insight into the principles that determine the nature and organization of these dynamic structures, we analyze this behavior by modeling the 2D actomyosin cell cortex as an active fluid medium. The numerical simulations show that the stability of the actin filaments influences the spatial structure and dynamics of the system. We find that in addition to static Turing-type patterns, persistent dynamic behavior occurs in a wide range of parameters. In the 2D model, mechanical stress-dependent actin breakdown is shown to produce a continuously changing network of actin bridges, whereas with a constant breakdown rate, more isolated clusters of actomyosin tend to form. The model qualitatively reproduces the dynamic and stable patterns experimentally observed at the junctions between epithelial cells.

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

“…CLDN1 holds cells together which counteracts the pulling force. These features provide a potential linkage between oscillatory actomyosin forces and oscillatory HES1 expression . Gene regulatory circuits containing cell and developmental stage‐specific transcription factors forming “a two‐gene network with two repressors” that bind each other's promoters have been proposed as “hardwiring” required for stable equilibrium of cell types in “Mathematics of the Genome” involving “n‐Dimensional Dynamical Systems” .…”

“…These features provide a potential linkage between oscillatory actomyosin forces and oscillatory HES1 expression. 10,11 Gene regulatory circuits containing cell and developmental stage-specific transcription factors forming "a two-gene network with two repressors" that bind each other's promoters have been proposed as "hardwiring" required for stable equilibrium of cell types in "Mathematics of the Genome" involving "n-Dimensional Dynamical Systems". 5 We observed potential "toggle gene circuits" as proposed involving the transcription factors HES1 and NR3C1 (glucocorticoid receptor, GR) that regulate CLDN1 along the human colon crypt axis, and in vitro Caco-2 cell differentiation.…”

Rotational 3D mechanogenomic Turing patterns of human colon Caco-2 cells during differentiation

“…Single cell genome labelled with DAPI can be found in a torus shape. OCLN protein showed circular wave pattern, this pattern may correlate with actomyosin force [36]. Formation of “ring of cells” proposed by Turing may start from 1 to 2 cells, the HES1 distribution may conform to “The morphogen pattern in a ring of cells as deduced by Turing” [17].…”

“…NR3C1 showed wave peak pattern comes from the spiral axis. OCLN’s circular wave pattern may correlate with actomyosin force [36]. The shape of the nucleuses looks conform to actomyosin Rho GTPase shape in a model of the rotational motion of polarized mammalian epithelial cells on micropatterns [19].…”

“…Diffusion of the transcription factor NR3C1 and HES1 from the hole can be seen. This pattern may correlate with actomyosin force [36]. The shape of genome may conform to a “Hopf bifurcation” used to illustrate the mathematics of the genome [6].…”