Mechano-lithography: stress anisotropy driven nematic order in growing three-dimensional bacterial biofilms

TL;DR

This study uses an agent-based model to reveal how stress anisotropy influences nematic order in 3D bacterial biofilms, uncovering a mechano-biological mechanism of pattern formation with potential biomedical applications.

Contribution

It demonstrates that stress anisotropy drives nematic ordering in confined biofilms, providing new insights into the physical mechanisms of multicellular pattern emergence.

Findings

Stress buildup is heterogeneous within biofilms.

Core stresses promote disorder, interface stresses promote order.

Stress anisotropy correlates with cell nematic order over time.

Abstract

Living active collectives have evolved with remarkable self-patterning ability to meet the physical and biological constraints for growth and survival. However, how complex multicellular patterns emerge from a single founder cell remains elusive. Here, by recourse to an agent-based model, we track the three-dimensional (3D) morphodynamics and cell orientational order of growing bacterial biofilms encased by agarose gels. Confined growth causes spatiotemporally heterogeneous stress buildup in the biofilm. High hydrostatic and low shear stresses at the core of the biofilm promote viscous-to-elastic transition and randomize cell packing, whereas the opposite stress state near the gel-cell interface drives nematic ordering with a time delay inherent to shear stress relaxation. Overall, stress anisotropy spatiotemporally coincides with nematic order in the confined biofilms, suggesting an anisotropic-stress-driven ordering mechanism. The strong reciprocity between stress anisotropy and cell ordering inspires innovative 3D mechano-lithography of living active collectives for a variety of environmental and biomedical applications.