Continuum percolation theory of epimorphic regeneration

TL;DR

This paper introduces a biophysical continuum percolation model for epimorphic regeneration, explaining how cellular connectivity influences organism morphology and symmetry, with applications to planaria regeneration.

Contribution

It presents a novel biophysical model linking cellular connectivity to regenerative morphology, validated by experimental observations in planaria.

Findings

Model accurately predicts anterior-posterior polarization.

Explains formation of four-headed planaria.

Shows connectivity degradation leads to symmetrical structures.

Abstract

A biophysical model of epimorphic regeneration based on a continuum percolation process of fully penetrable disks in two dimensions is proposed. All cells within a randomly chosen disk of the regenerating organism are assumed to receive a signal in the form of a circular wave as a result of the action/reconfiguration of neoblasts and neoblast-derived mesenchymal cells in the blastema. These signals trigger the growth of the organism, whose cells read, on a faster time scale, the electric polarization state responsible for their differentiation and the resulting morphology. In the long time limit, the process leads to a morphological attractor that depends on experimentally accessible control parameters governing the blockage of cellular gap junctions and, therefore, the connectivity of the multicellular ensemble. When this connectivity is weakened, positional information is degraded leading to more symmetrical structures. This general theory is applied to the specifics of planaria regeneration. Computations and asymptotic analyses made with the model show that it correctly describes a significant subset of the most prominent experimental observations, notably anterior-posterior polarization (and its loss) or the formation of four-headed planaria.