Sensing the shape of a cell with reaction-diffusion and energy minimization

Abstract: Some dividing cells sense their shape by becoming polarized along their long axis. Cell polarity is controlled in part by polarity proteins like Rho GTPases cycling between active membrane-bound forms and inactive cytosolic forms, modeled as a "wave-pinning" reaction-diffusion process. Does shape sensing emerge from wave-pinning? We show that wave pinning senses the cell's long axis. Simulating wave-pinning on a curved surface, we find that high-activity domains migrate to peaks and troughs of the surface. For smooth surfaces, a simple rule of minimizing the domain perimeter while keeping its area fixed predicts the final position of the domain and its shape. However, when we introduce roughness to our surfaces, shape sensing can be disrupted, and high-activity domains can become localized to locations other than the global peaks and valleys of the surface. On rough surfaces, the domains of the wave-pinning model are more robust in finding the peaks and troughs than the minimization rule, though both can become trapped in steady states away from the peaks and valleys. We can control the robustness of shape sensing by altering the Rho GTPase diffusivity and the domain size. We also find that the shape sensing properties of cell polarity models can explain how domains localize to curved regions of deformed cells. Our results help to understand the factors that allow cells to sense their shape - and the limits that membrane roughness can place on this process.