TY - JOUR
T1 - The role of intracellular interactions in the collective polarization of tissues and its interplay with cellular geometry
AU - Shadkhoo, Shahriar
AU - Mani, Madhav
N1 - Publisher Copyright:
© 2019 Shadkhoo, Mani. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2019
Y1 - 2019
N2 - Planar cell polarity (PCP), the long-range in-plane polarization of epithelial tissues, provides directional information that guides a multitude of developmental processes at cellular and tissue levels. While it is manifest that cells utilize both intracellular and intercellular interactions, the coupling between the two modules, essential to the coordination of collective polarization, remains an active area of investigation. We propose a generalized reaction- diffusion model to study the role of intracellular interactions in the emergence of longrange polarization, and show that the nonlocality of cytoplasmic interactions, i.e. coupling of membrane proteins localized on different cell-cell junctions, is of vital importance to the faithful detection of weak directional signals, and becomes increasingly more crucial to the stability of polarization against the deleterious effects of large geometric irregularities. We demonstrate that nonlocal interactions are necessary for geometric information to become accessible to the PCP components. The prediction of the model regarding polarization in elongated tissues, is shown to be in agreement with experimental observations, where the polarity emerges perpendicular to the axis of elongation. Core PCP is adopted as a model pathway, in term of which we interpret the model parameters. To this end, we introduce three distinct classes of mutations, (I) in membrane proteins, (II) in cytoplasmic proteins, and (III) local enhancement of geometric disorder. Comparing the in silico and in vivo phenotypes, we show that our model successfully recapitulates the salient phenotypic features of these mutations. Exploring the parameter space helps us shed light on the role of cytoplasmic proteins in cell-cell communications, and make falsifiable predictions regarding the cooperation of cytoplasmic and membrane proteins in the establishment of longrange polarization.
AB - Planar cell polarity (PCP), the long-range in-plane polarization of epithelial tissues, provides directional information that guides a multitude of developmental processes at cellular and tissue levels. While it is manifest that cells utilize both intracellular and intercellular interactions, the coupling between the two modules, essential to the coordination of collective polarization, remains an active area of investigation. We propose a generalized reaction- diffusion model to study the role of intracellular interactions in the emergence of longrange polarization, and show that the nonlocality of cytoplasmic interactions, i.e. coupling of membrane proteins localized on different cell-cell junctions, is of vital importance to the faithful detection of weak directional signals, and becomes increasingly more crucial to the stability of polarization against the deleterious effects of large geometric irregularities. We demonstrate that nonlocal interactions are necessary for geometric information to become accessible to the PCP components. The prediction of the model regarding polarization in elongated tissues, is shown to be in agreement with experimental observations, where the polarity emerges perpendicular to the axis of elongation. Core PCP is adopted as a model pathway, in term of which we interpret the model parameters. To this end, we introduce three distinct classes of mutations, (I) in membrane proteins, (II) in cytoplasmic proteins, and (III) local enhancement of geometric disorder. Comparing the in silico and in vivo phenotypes, we show that our model successfully recapitulates the salient phenotypic features of these mutations. Exploring the parameter space helps us shed light on the role of cytoplasmic proteins in cell-cell communications, and make falsifiable predictions regarding the cooperation of cytoplasmic and membrane proteins in the establishment of longrange polarization.
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U2 - 10.1371/journal.pcbi.1007454
DO - 10.1371/journal.pcbi.1007454
M3 - Article
C2 - 31770364
AN - SCOPUS:85076002318
SN - 1553-734X
VL - 15
JO - PLoS computational biology
JF - PLoS computational biology
IS - 11
M1 - e1007454
ER -