Surface tension determines tissue shape and growth kinetics

Ehrig, Sebastian; Bidan, Cécile M.; West, Alan C.; Jacobi, Cornelius; Lam, Karen; Kollmannsberger, Philip; Petersen, Ansgar; Tomančák, Pavel; Kommareddy, Krishna P.; Fischer, Franz Dieter; Fratzl, Peter; Dunlop, John

doi:10.1101/456228

Cited by 4 publications

(10 citation statements)

References 33 publications

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“…Only the interface of the tissue is evolved, with no consideration of the correlation between volumetric tissue growth, and cell proliferation or tissue synthesis. In our cell bridging experiments in Figure 1, the rounding off of the tissue interface at corners of the initial pores suggests that tissue grows preferentially where curvature is high, consistently with other studies [11][12][13]15]. Because the tissue interface evolves through a series of shapes with increasing curvature, it is not obvious why the time required to bridge the pores in these scaffolds varies linearly with initial pore size ( Figure 2).…”

Section: Discussionsupporting

confidence: 82%

“…In engineered tissue scaffolds, tissue grown by osteoblastderived cells in pores of different shapes is also observed to be regulated by geometry. The local rate of growth is found to correlate with the curvature of the tissue [11][12][13], and thought to be due to tissue surface tension driving cell proliferation [12][13][14][15]. Phenomenological models that describe these scaffold experiments assume that the evolution of the tissue interface is governed by mean curvature flows, by analogy with surface-tension-induced mean curvature flows that arises in the evolution of bubbles in fluid mechanics.…”

Section: Discussionmentioning

confidence: 99%

“…There are many design questions that need to be addressed in the production of these scaffolds, such as determining their optimal size, shape and material properties [2][3][4]. These properties have been shown to impact cell attachment, viability, proliferation, migration, and differentiation, among other functions [10][11][12][13][14][15][16], and they could be tuned to control the manufacture of complex multicellular tissues or organs. Recent additive manufacturing techniques have leveraged these biophysical relationships in an ad hoc manner: by 3D printing bilayer cylindrical scaffolds as vascular grafts with endothelial and muscle cells [17] or by patterning scaffold pores or fibres * Corresponding author: pascal.buenzli@qut.edu.au to spatially control cell morphology and differentiation [18].…”

Section: Introductionmentioning

confidence: 99%

“…Cellular tensile stress correlates with cell proliferation in a number of experimental situations, including in tissue engineering and wound healing [10,19,20]. At the tissue interface, contractile actomyosin rings induce a tissue surface tension [21] subject to a curvature dependence similar to that of surface tension in fluids [11,12,15]. It is therefore expected that tissue curvature influences cell proliferation and thus tissue growth.…”

Section: Introductionmentioning

confidence: 99%

“…Several mathematical modelling strategies have been developed to explore the interplay between tissue growth and curvature effects [16], such as models based on the idea of mean curvature flow, that borrow ideas from fluid mechanics and the role of surface tension, but that do not consider cells explicitly [11][12][13][14][15]. Other modelling approaches consider the effects of cell-level behaviour and tissue crowding and spreading during surface growth, which lead to hyperbolic curvature flow models [24,22,25].…”

Section: Introductionmentioning

confidence: 99%

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Cell proliferation and migration explain pore bridging dynamics in 3D printed scaffolds of different pore size

Buenzli

Lanaro

Wong

et al. 2020

Preprint

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Tissue growth in bioscaffolds can be influenced significantly by pore geometry, but how this geometric dependence emerges from dynamic cellular processes such as cell proliferation and cell migration remains poorly understood. Here we investigate the influence of pore size on the time required to bridge pores in a 3D printed scaffold by analysing experiments with a mathematical model. Experimentally, the new tissue infills the pore continually from the pore perimeter under strong curvature control, which leads to rounding off of the initial pore shape. Despite the varied shapes assumed by the tissue during this evolution, we find that time to bridge the pore simply increases linearly with the overall pore size. To disentangle the biological influence of cell behaviour and the mechanistic influence of geometry in this experimental observation, we propose a simple reaction-diffusion model of tissue growth based on Porous-Fisher invasion of cells into the pores. First, this model provides a good qualitative representation of the evolution of the tissue; new cellular tissue in the model grows at a rate that depends on the local curvature of the tissue substrate. Second, the model suggests that a linear dependence of bridging time with pore size arises due to geometric reasons alone, not to differences in cell behaviours across pores of different sizes. Our analysis therefore suggests that tissue growth dynamics in these experimental constructs is dominated by mechanistic cell proliferation and cell diffusion processes. The rates of these processes are unaffected by pore geometry, and can be predicted by simple reaction-diffusion models of cells that have robust, consistent behaviours.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Cell proliferation and migration explain pore bridging dynamics in 3D printed scaffolds of different pore size

Buenzli

Lanaro

Wong

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

Cell proliferation and migration explain pore bridging dynamics in 3D printed scaffolds of different pore size

et al. 2020

View full text Add to dashboard Cite

Tissue growth in bioscaffolds is influenced significantly by pore geometry, but how this geometric dependence emerges from dynamic cellular processes such as cell proliferation and cell migration remains poorly understood. Here we investigate the influence of pore size on the time required to bridge pores in thin 3D-printed scaffolds. Experimentally, new tissue infills the pores continually from their perimeter under strong curvature control, which leads the tissue front to round off with time. Despite the varied shapes assumed by the tissue during this evolution, we find that time to bridge a pore simply increases linearly with the overall pore size. To disentangle the biological influence of cell behaviour and the mechanistic influence of geometry in this experimental observation, we propose a simple reaction-diffusion model of tissue growth based on Porous-Fisher invasion of cells into the pores. First, this model provides a good qualitative representation of the evolution of the tissue; new tissue in the model grows at an effective rate that depends on the local curvature of the tissue substrate. Second, the model suggests that a linear dependence of bridging time with pore size arises due to geometric reasons alone, not to differences in cell behaviours across pores of different sizes. Our analysis suggests that tissue growth dynamics in these experimental constructs is dominated by mechanistic crowding effects that influence collective cell proliferation and migration processes, and that can be predicted by simple reaction-diffusion models of cells that have robust, consistent behaviours.

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Surface and Bulk Stresses Drive Morphological Changes in Fibrous Microtissues

Mailand

Eyckmans

et al. 2019

Biophysical Journal

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Engineered fibrous tissues consisting of cells encapsulated within collagen gels are widely used three-dimensional in vitro models of morphogenesis and wound healing. Although cell-mediated matrix remodeling that occurs within these scaffolds has been extensively studied, less is known about the mesoscale physical principles governing the dynamics of tissue shape. Here, we show both experimentally and by using computer simulations how surface contraction through the development of surface stresses (analogous to surface tension in fluids) coordinates with bulk contraction to drive shape evolution in constrained three-dimensional microtissues. We used microelectromechanical systems technology to generate arrays of fibrous microtissues and robot-assisted microsurgery to perform local incisions and implantation. We introduce a technique based on phototoxic activation of a small molecule to selectively kill cells in a spatially controlled manner. The model simulations, which reproduced the experimentally observed shape changes after surgical and photochemical operations, indicate that fitting of only bulk and surface contractile moduli is sufficient for the prediction of the equilibrium shape of the microtissues. The computational and experimental methods we have developed provide a general framework to study and predict the morphogenic states of contractile fibrous tissues under external loading at multiple length scales.

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Surface tension determines tissue shape and growth kinetics

Cited by 4 publications

References 33 publications

Cell proliferation and migration explain pore bridging dynamics in 3D printed scaffolds of different pore size

Cell proliferation and migration explain pore bridging dynamics in 3D printed scaffolds of different pore size

Cell proliferation and migration explain pore bridging dynamics in 3D printed scaffolds of different pore size

Surface and Bulk Stresses Drive Morphological Changes in Fibrous Microtissues

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