Molecular-scale substrate anisotropy and crowding drive long-range nematic order of cell monolayers

TL;DR

This study demonstrates that molecular-scale substrate anisotropy and cell crowding induce long-range nematic order in cell monolayers, revealing mechanisms of cellular organization relevant to tissue engineering.

Contribution

It introduces a high-throughput imaging platform and uncovers how substrate anisotropy and cell division promote nematic order in cell collectives.

Findings

Substrate anisotropy directs cell alignment.

Cell division along nematic axes enhances order.

Cells exhibit extensile stresses restructuring actomyosin networks.

Abstract

The ability of cells to reorganize in response to external stimuli is important in areas ranging from morphogenesis to tissue engineering. Elongated cells can co-align due to steric effects, forming states with local order. We show that molecular-scale substrate anisotropy can direct cell organization, resulting in the emergence of nematic order on tissue scales. To quantitatively examine the disorder-order transition, we developed a high-throughput imaging platform to analyze velocity and orientational correlations for several thousand cells over days. The establishment of global, seemingly long-ranged order is facilitated by enhanced cell division along the substrate's nematic axis, and associated extensile stresses that restructure the cells' actomyosin networks. Our work, which connects to a class of systems known as active dry nematics, provides a new understanding of the dynamics of cellular remodeling and organization in weakly interacting cell collectives. This enables data-driven discovery of cell-cell interactions and points to strategies for tissue engineering.