On the correlation between material-induced cell shape and phenotypical response of human mesenchymal stem cells

Aliaksei S. Vasilevich,Nadia Roumans,Shantanu Singh,Said Eroumé,Aurélie Carlier,Rika Reihs,Nick R. M. Beijer,Dennie G. A. J. Hebels,Anne E. Carpenter,Jeroen van de Peppel,Jan de Boer,Steven Vermeulen,Marloes Kamphuis

doi:10.1038/s41598-020-76019-z

Aliaksei S. Vasilevich, Nadia Roumans + Show 11 more

Open Access

https://doi.org/10.1038/s41598-020-76019-z

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Abstract

Learning rules by which cell shape impacts cell function would enable control of cell physiology and fate in medical applications, particularly, on the interface of cells and material of the implants. We defined the phenotypic response of human bone marrow-derived mesenchymal stem cells (hMSCs) to 2176 randomly generated surface topographies by probing basic functions such as migration, proliferation, protein synthesis, apoptosis, and differentiation using quantitative image analysis. Clustering the surfaces into 28 archetypical cell shapes, we found a very strict correlation between cell shape and physiological response and selected seven cell shapes to describe the molecular mechanism leading to phenotypic diversity. Transcriptomics analysis revealed a tight link between cell shape, molecular signatures, and phenotype. For instance, proliferation is strongly reduced in cells with limited spreading, resulting in down-regulation of genes involved in the G2/M cycle and subsequent quiescence, whereas cells with large filopodia are related to activation of early response genes and inhibition of the osteogenic process. In this paper we were aiming to identify a universal set of genes that regulate the material-induced phenotypical response of human mesenchymal stem cells. This will allow designing implants that can actively regulate cellular, molecular signalling through cell shape. Here we are proposing an approach to tackle this question.

Highlights

Learning rules by which cell shape impacts cell function would enable control of cell physiology and fate in medical applications, on the interface of cells and material of the implants
We observed a continuum of cell shapes with some densely and sparsely occupied areas, demonstrating that some shape features are more abundant in our shape collection than others
This was confirmed by hierarchical clustering, where the tree structure displays four distinct branches, which are further divided until it reaches single cell shapes (Fig. 1d)

Summary

Introduction

Learning rules by which cell shape impacts cell function would enable control of cell physiology and fate in medical applications, on the interface of cells and material of the implants. In this paper we were aiming to identify a universal set of genes that regulate the material-induced phenotypical response of human mesenchymal stem cells. This will allow designing implants that can actively regulate cellular, molecular signalling through cell shape. Experimental evidence for “function follows shape” comes from in vitro experiments where cell shape can be controlled using micropatterning techniques Basic cellular decisions such as differentiation, apoptosis or metabolic rate can be controlled by merely controlling cell shape[14], suggesting that cell shapes generate signals which are transduced into the nucleus and result in changes in gene and protein expression[15]. These cells are multipotent, their progeny has very distinct differences in cell shape and there is ample evidence for shape-directed differentiation

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