Cell Shape and Forces in Elastic and Structured Environments: From Single Cells to Organoids

Abstract

With the advent of mechanobiology, cell shape and forces have emerged as essential elements of cell behavior and fate, in addition to biochemical factors such as growth factors. Cell shape and forces are intrinsically linked to the physical properties of the environment. Extracellular stiffness guides migration of single cells and collectives as well as differentiation and developmental processes. In confined environments, cell division patterns are altered, cell death or extrusion might be initiated, and other modes of cell migration become possible. Tools from materials science such as adhesive micropatterning of soft elastic substrates or direct laser writing of 3D scaffolds have been established to control and quantify cell shape and forces in structured environments. Herein, a review is given on recent experimental and modeling advances in this field, which currently moves from single cells to cell collectives and tissue. A very exciting avenue is the combination of organoids with structured environments, because this will allow one to achieve organotypic function in a controlled setting well suited for long‐term and high‐throughput culture.

Mesenchymal cell migration on one-dimensional micropatterns

“…Some models hypothesize dynamics such as protrusion formation and shape oscillations to arise from signaling especially by small GTPases ( Danuser et al, 2013 ; Rappel and Edelstein-Keshet, 2017 ; Bolado-Carrancio et al, 2020 ; Shaebani et al, 2020 ). Another group of models considers the signaling state of the cell as constant, setting the parameters for a dynamic mechanical system of cytoplasmic and F-actin flows, Myosin II based contraction and membrane dynamics ( Kruse et al, 2005 ; Safran et al, 2005 ; Jülicher et al, 2007 ; Gholami et al, 2008 ; Enculescu et al, 2010 ; Zimmermann et al, 2010 ; Shaebani et al, 2020 ; Link et al, 2023 ). The modeling approaches have been described in several reviews ( Romanczuk et al, 2012 ; Ryan et al, 2012 ; Danuser et al, 2013 ; Alert and Trepat, 2020 ; Shaebani et al, 2020 ; Link et al, 2023 ; Zöttl and Stark, 2023 ).…”

“…Another group of models considers the signaling state of the cell as constant, setting the parameters for a dynamic mechanical system of cytoplasmic and F-actin flows, Myosin II based contraction and membrane dynamics ( Kruse et al, 2005 ; Safran et al, 2005 ; Jülicher et al, 2007 ; Gholami et al, 2008 ; Enculescu et al, 2010 ; Zimmermann et al, 2010 ; Shaebani et al, 2020 ; Link et al, 2023 ). The modeling approaches have been described in several reviews ( Romanczuk et al, 2012 ; Ryan et al, 2012 ; Danuser et al, 2013 ; Alert and Trepat, 2020 ; Shaebani et al, 2020 ; Link et al, 2023 ; Zöttl and Stark, 2023 ). Here, we focus on modeling studies specifically for 1D motion.…”

Recent Advances in Multi‐Photon 3D Laser Printing: Active Materials and Applications

“…Confined spaces or printed structures can lead to cell alignment or induce changes within cells leading for example to stem cell differentiation into certain cell types. [86,195,[203][204][205][206][207] For a detailed overview and analysis of these effects on single cells, we kindly refer to a recent review on this topic by Link et al [208] Recently, the investigation of single cells in dynamic environments has become possible by employing printable materials, whose properties can be changed on demand upon external stimuli. One of the first examples of such a material was presented by Hippler et al in 2020 (see Figure 7B).…”

“…[ 86,195,203–207 ] For a detailed overview and analysis of these effects on single cells, we kindly refer to a recent review on this topic by Link et al. [ 208 ]…”

Modelling cell shape in 3D structured environments: A quantitative comparison with experiments

“…Mathematical modelling plays an important role in improving and validating our understanding of cell shape, especially if combined with quantitative experiments. Simulating cell shape in structured environments tests and increases our understanding of the underlying mechanisms governing cell behavior [ 16 ]. Analytical 2D cell shape models have been developed to predict cell shape on micropatterned environments using line and surface tensions [ 17 , 18 ], and the notion that the contractile actin cortex is responsible for 3D cell shape is wide-spread [ 19 , 20 ].…”