Emergent patterns of growth controlled by multicellular form and mechanics

TLDR

Cellular growth patterns generate mechanical stresses that shape tissues, while genetic factors are believed to specify these growth patterns and other morphogenetic behaviors. The study demonstrates that tissue morphology can feedback to regulate proliferation patterns. Micro‑fabricated cell sheets were used to induce stable proliferative foci, revealing how tissue organization drives growth patterns. Concentrated growth occurred where tractional stress was highest, as predicted by a finite‑element model and confirmed with micromechanical sensors; disrupting actomyosin tension or cadherin links abolished the pattern, showing that cell‑generated mechanical forces arising from multicellular organization regulate tissue growth.

Abstract

Spatial patterns of cellular growth generate mechanical stresses that help to push, fold, expand, and deform tissues into their specific forms. Genetic factors are thought to specify patterns of growth and other behaviors to drive morphogenesis. Here, we show that tissue form itself can feed back to regulate patterns of proliferation. Using micro-fabrication to control the organization of sheets of cells, we demonstrated the emergence of stable patterns of proliferative foci. Regions of concentrated growth corresponded to regions of high tractional stress generated within the sheet, as predicted by a finite-element model of multicellular mechanics and measured directly by using a micromechanical force sensor array. Inhibiting actomyosin-based tension or cadherin-mediated connections between cells disrupted the spatial pattern of proliferation. These findings demonstrate the existence of patterns of mechanical forces that originate from the contraction of cells, emerge from their multicellular organization, and result in patterns of growth. Thus, tissue form is not only a consequence but also an active regulator of tissue growth.