Modulation of collective cell behaviour by geometrical constraints.

Mariia Lunova,Vitalii Zablotskii,Alexandr Dejneka,Thibaut Devillers,Nora M Dempsey,Oleg Lunov,Šárka Kubinová,Eva Syková,Milan Jirsa

doi:10.1039/c6ib00125d

Abstract

Intracellular and extracellular mechanical forces play a crucial role during tissue growth, modulating nuclear shape and function and resulting in complex collective cell behaviour. However, the mechanistic understanding of how the orientation, shape, symmetry and homogeneity of cells are affected by environmental geometry is still lacking. Here we investigate cooperative cell behaviour and patterns under geometric constraints created by topographically patterned substrates. We show how cells cooperatively adopt their geometry, shape, positioning of the nucleus and subsequent proliferation activity. Our findings indicate that geometric constraints induce significant squeezing of cells and nuclei, cytoskeleton reorganization, drastic condensation of chromatin resulting in a change in the cell proliferation rate and the anisotropic growth of cultures. Altogether, this work not only demonstrates complex non-trivial collective cellular responses to geometrical constraints but also provides a tentative explanation of the observed cell culture patterns grown on different topographically patterned substrates. These findings provide important fundamental knowledge, which could serve as a basis for better controlled tissue growth and cell-engineering applications.

Highlights

IntroductionCell colonies (populations) may exhibit a wide variety of exquisite spatial and temporal patterns
During tissue growth, cell colonies may exhibit a wide variety of exquisite spatial and temporal patterns
To produce uniform substrates for biological applications, we utilized deep reactive ion etching to pattern Si wafers so as to produce sets of substrates with surfaces consisting of arrays of silicon micropillars of different geometry and with different values of inter-pillar spacing

Summary

Introduction

Cell colonies (populations) may exhibit a wide variety of exquisite spatial and temporal patterns. Being the outcome of coordinated cell growth, movement, and cell–cell communications that involve the detection and processing of extracellular forces and cues, these patterns often play vital roles in organ growth and development.[1] the origin and mechanism of the pattern formation remain unclear. The structured microenvironments that surround cells within organs and tissues possess particular shape constraints. Such constraints provide the basis for regulation of the cellular function.[2,3,4,5] For a Institute for Clinical & Experimental Medicine (IKEM), Prague, Czech Republic b Institute of Physics of the Academy of Sciences of the Czech Republic, The question of how physical forces and the geometry of the cell microenvironment regulate cooperative cellular function remains open. Numerous lines of research have begun to reveal that the geometry of the cell microenvironment is a critical parameter for regulating cell fate.[11,16,17] The tentative explanation of how cell shape data are transduced into gene expression has been proposed in ref

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