Delayed self-regulation leads to novel states in epigenetic landscapes

The epigenetic pathway of a cell as it differentiates from a stem cell state to a mature lineage-committed one has been historically understood in terms of Waddingtons landscape, consisting of hills and valleys. The smooth top and valley-strewn bottom of the hill represents their undifferentiated and differentiated states respectively. Although mathematical ideas rooted in nonlinear dynamics and bifurcation theory have been used to quantify this picture, the importance of time delays arising from multistep chemical reactions or cellular shape transformations have been ignored so far. We argue that this feature is crucial in understanding cell differentiation and explore the role of time delay in a model of a single gene regulatory circuit. We show that the interplay of time-dependant drive and delay introduces a new regime where the system shows sustained oscillations between the two admissible steady states. We interpret these results in the light of recent perplexing experiments on inducing the pluripotent state in mouse somatic cells. We also comment on how such an oscillatory state can provide a framework for understanding more general feedback circuits in cell development.

Thermodynamic behaviour of two-dimensional vesicles revisited

We study pressurised self-avoiding ring polymers in two dimensions using Monte Carlo simulations, scaling arguments and Flory-type theories, through models which generalise the model of Leibler, Singh and Fisher [Phys. Rev. Lett. Vol. 59, 1989 (1987)]. We demonstrate the existence of a thermodynamic phase transition at a non-zero scaled pressure $tilde{p}$, where $tilde{p} = Np/4pi$, with the number of monomers $N rightarrow infty$ and the pressure $p rightarrow 0$, keeping $tilde{p}$ constant, in a class of such models. This transition is driven by bond energetics and can be either continuous or discontinuous. It can be interpreted as a shape transition in which the ring polymer takes the shape, above the critical pressure, of a regular N-gon whose sides scale smoothly with pressure, while staying unfaceted below this critical pressure. In the general case, we argue that the transition is replaced by a sharp crossover. The area, however, scales with $N^2$ for all positive $p$ in all such models, consistent with earlier scaling theories.