Mechanochemical feedback regulates the dynamics of the PAR system in C. elegans zygotes

Abstract

The interplay between regulatory biochemistry and cell mechanics is critical for a broad range of morphogenetic changes. Cell mechanics can induce transport via growth and flow-fields, which in turn affect concentration-fields of regulators. Such systems exhibit an intrinsic feedback-architecture between regulators of cell mechanics and mechanical deformation. While we anticipate that this feedback between biochemistry and cell mechanics is widespread in Morphogenesis, there are few examples that are studied with respect to their potential for generating spatiotemporal patterns. Here we establish at a quantitative level that PAR polarization of C. elegans zygotes represents a coupled mechanochemical system. Using Fluorescence Recovery After Photobleaching (FRAP) and RNA interference (RNAi), we first demonstrate that the biochemistry in form of the PAR domains feeds back on the mechanics by establishing and maintaining a non-muscle myosin II (nmy-2) gradient. Additionally, we characterize the effect of the polarity cue associated with the centrosome of the male pronucleus on the local myosin concentration at the posterior pole. We show that it induces a reduction in myosin concentration and thereby triggers the onset of cortical flows. Furthermore we measure the spatiotemporal profile of the anterior and posterior PAR concentration, the myosin II concentration and the induced flow-field. Finally, we capture the feedback-architecture of the coupled actomyosin – PAR system in a quantitative model, based on coupling a thin film active fluid description of cortical mechanics [1] to a reaction-diffusion PAR patterning system [2]. We show that this mathematical model can quantitatively recapitulate the spatiotemporal profile of PAR polarity establishment. Furthermore, we demonstrate that the model predicts the existence of a threshold in cortical flow velocity, which separates the nonpolarizing and the polarizing regime and confirm the existence of this threshold velocity in the living C. elegans zygote.