On the origin of universal cell shape variability in confluent epithelial monolayers

Abstract

Cell shape is fundamental in biology. The average cell shape can influence crucial biological functions, such as cell fate and division orientation. But cell-to-cell shape variability is often regarded as noise. In contrast, recent works reveal that shape variability in diverse epithelial monolayers follows a nearly universal distribution. However, the origin and implications of this universality remain unclear. Here, assuming contractility and adhesion are crucial for cell shape, characterized via aspect ratio (r), we develop a mean-field analytical theory for shape variability. We find that all the system-specific details combine into a single parameter α that governs the probability distribution function (PDF) of r; this leads to a universal relation between the standard deviation and the average of r. The PDF for the scaled r is not strictly but nearly universal. In addition, we obtain the scaled area distribution, described by the parameter μ, α and μ together can distinguish the effects of changing physical conditions, such as maturation, on different system properties. We have verified the theory via simulations of two distinct models of epithelial monolayers and with existing experiments on diverse systems. We demonstrate that in a confluent monolayer, average shape determines both the shape variability and dynamics. Our results imply that cell shape distribution is inevitable, where a single parameter describes both statics and dynamics and provides a framework to analyze and compare diverse epithelial systems. In contrast to existing theories, our work shows that the universal properties are consequences of a mathematical property and should be valid in general, even in the fluid regime.

How motility drives the glassy dynamics in confluent epithelial monolayers?

“…Our work provides a theoretical framework to understand the nontrivial nature of relaxation dynamics in these systems. Theoretical studies till now have treated the two crucial aspects of biological systems, confluency [57,69], and motility [21,46,47,[49][50][51], separately. Here, for the first time, we have included both aspects within a single theoretical framework and reveal novel features of motility-driven glassy dynamics in confluent epithelial systems.…”

“…Compared to most particulate systems, confluent systems readily show sub-Arrhenius relaxation dynamics [60,64,70], and cellular shape is a crucial control parameter for these systems [32,71]. Moreover, the same system also shows super-Arrhenius behavior with changing control parameters.…”

Active nematics with deformable particles

“…35 Mean field theories of cell shape variations based on the vertex cellular Potts models have also been presented. 36,37 We have focused on extensile materials. Contractile systems which are initially circular will not show any dynamical behaviour because active forces just reinforce the thermodynamic forces restoring the particles to circular.…”

“…35 Mean field theories of cell shape variations based on the vertex cellular Potts models have also been presented. 36,37…”

Synthetic Cells Revisited: Artificial Cell Construction Using Polymeric Building Blocks

“…Shape plays a fundamental role in many cellular functions including growth and division, apoptosis, and motility. [ 233 ] As functional units of a tissue, shape changes at the cellular level are important determinants of development and are also associated with many pathological conditions such as cancer. Many communication pathways in eukaryotic cells involve shape changes, frequently based on cytoskeleton dynamics.…”