Bistability to Quad-stability: Emergence of Hybrid Phenotypes & Enhanced Spatio-temporal Plasticity in Presence of Host-Circuit Coupling

TL;DR

This paper investigates how resource competition, growth feedback, and spatial diffusion in gene regulatory networks lead to multiple phenotypes and dynamic spatial behaviors, offering insights into cancer progression.

Contribution

It reveals how growth-induced resource competition and diffusion jointly cause phenotypic diversity and spatiotemporal plasticity in cellular systems, especially in cancer.

Findings

Emergence of multiple phenotypes under high resource competition.

Spatial diffusion influences the stability and dynamics of phenotypic states.

Growth feedback and diffusion asymmetry drive complex spatial behaviors.

Abstract

In the context of multistability driven diseases, like cancer, spatiotemporal plasticity plays a significant role to achieve a spectrum of phenotypic variations. The interplay between gene regulatory networks and environmental factors, such as resource competition and spatial diffusion, plays a crucial role in determining cellular behaviour and phenotypic heterogeneity. Though reaction diffusion frameworks have been widely applied in developmental biology, less attention has been paid to the simultaneous effects of resource competition and growth feedback on spatial organization. In this paper, we observed that a bistable genetic circuit under high resource competition due to growth feedback gives rise to multiple emergent phenotypes, as observed in cancer systems. Furthermore, we observed how spatial diffusion coupled with intrinsic nonlinearity can drive the emergence of distinct spatial dynamics over time. The observed spatiotemporal plasticity can also be driven by the comparative stability of the fixed points, diffusivity, and asymmetry of diffusion. Our findings highlight that growth-induced resource competition combined with diffusion can provide deeper insights into metastasis and cancer progression.