scholarly journals Coupling intercellular molecular signalling with multicellular deformation for simulating three-dimensional tissue morphogenesis

2015 ◽  
Vol 5 (2) ◽  
pp. 20140095 ◽  
Author(s):  
Satoru Okuda ◽  
Yasuhiro Inoue ◽  
Tadashi Watanabe ◽  
Taiji Adachi

During morphogenesis, three-dimensional (3D) multicellular structures emerge from biochemical and mechanical interplays among cells. In particular, by organizing their gradient within tissues, the diffusible signalling molecules play an essential role in producing the spatio-temporal patterns of cell status such as the differentiation states. Notably, this biochemical patterning can be dynamically coupled with multicellular deformations by signal-dependent cell activities such as contraction, adhesion, migration, proliferation and apoptosis. However, the mechanism by which these cellular activities mediate the interactions between multicellular deformations and patterning is still unknown. Herein, we propose a novel framework of a 3D vertex model to express molecular signalling among the mechanically deforming cells. By specifying a density of signalling molecules for each cell, we express their transport between neighbouring cells. By simulating signal-dependent epithelial growth, we found various types of tissue morphogenesis such as arrest, expansion, invagination and evagination. In the expansion phase, growth molecules were widely diffused with increasing tissue volume, which diluted the growth molecules in order to support the autonomous suppression of tissue growth. These results indicate that the proposed model successfully expresses 3D multicellular deformations dynamically coupled with biochemical patterning. We expect our proposed model to be a useful tool for predicting new phenomena emerging from mechanochemical coupling in multicellular morphogenesis.

2017 ◽  
Author(s):  
Mariam Veschgini ◽  
Hendrik O. Petersen ◽  
Stefan Kaufmann ◽  
Wasim Abuillan ◽  
Ryo Suzuki ◽  
...  

AbstractAlbeit ample evidence has suggested the remodeling of extracellular matrix (ECM) in animals plays crucial roles in development and diseases, little is understood how ECM mechanics correlates with tissue morphogenesis. In this study, we quantitatively determined how spatio-temporal elasticity patterns in ECM change during the asexual reproduction of freshwater polyp Hydra. We first determined the mesoscopic protein arrangement in Hydra ECM (mesoglea) by grazing-incidence small-angle X-ray scattering with nano-beam (nano-GISAXS). Our data unraveled fibrillar type I collagen in Hydra mesoglea (Hcol-I) takes an anisotropic, more strongly distorted hexagonal lattice compared to those in vertebrates that could be attributed to the lower proline content and lack of lysin-crosslinks in Hcol-1 fibers. Then, we “mapped” the spatio-temporal changes in ECM stiffness ex vivo with aid of nano-indentation. We identified three representative elasticity patterns during tissue growth along the oral-aboral body axis of the animals. Our complementary proteome analysis demonstrated that the elasticity patterns of the ECM correlate with a gradient like distribution of proteases. Perturbations of the oral Wnt/β-catenin signaling center further indicated that ECM elasticity patterns are governed by Wnt/β-catenin signaling. The ex vivo biomechanical phenotyping of Hydra mesoglea established in this study will help us gain comprehensive insights into the spatio-temporal coordination of biochemical and biomechanical cues in tissue morphogenesis in vivo.


2017 ◽  
Vol 115 (1) ◽  
pp. 70-74 ◽  
Author(s):  
Changjin Huang ◽  
David Quinn ◽  
Subra Suresh ◽  
K. Jimmy Hsia

Many applications in tissue engineering, flexible electronics, and soft robotics call for approaches that are capable of producing complex 3D architectures in soft materials. Here we present a method using molecular self-assembly to generate hydrogel-based 3D architectures that resembles the appealing features of the bottom-up process in morphogenesis of living tissues. Our strategy effectively utilizes the three essential components dictating living tissue morphogenesis to produce complex 3D architectures: modulation of local chemistry, material transport, and mechanics, which can be engineered by controlling the local distribution of polymerization inhibitor (i.e., oxygen), diffusion of monomers/cross-linkers through the porous structures of cross-linked polymer network, and mechanical constraints, respectively. We show that oxygen plays a role in hydrogel polymerization which is mechanistically similar to the role of growth factors in tissue growth, and the continued growth of hydrogel enabled by diffusion of monomers/cross-linkers into the porous hydrogel similar to the mechanisms of tissue growth enabled by material transport. The capability and versatility of our strategy are demonstrated through biomimetics of tissue morphogenesis for both plants and animals, and its application to generate other complex 3D architectures. Our technique opens avenues to studying many growth phenomena found in nature and generating complex 3D structures to benefit diverse applications.


2011 ◽  
Vol 11 (01) ◽  
pp. 231-272 ◽  
Author(s):  
DIEGO A. GARZÓN-ALVARADO ◽  
MARCO A. VELASCO ◽  
CARLOS A. NARVÁEZ-TOVAR

One area of tissue engineering concerns research into alternatives for new bone formation and replacing its function. Scaffolds have been developed to meet this requirement, allowing cell migration, bone tissue growth, transport of growth factors and nutrients, and the improvement of the mechanical properties of bone. Scaffolds are made from different biomaterials and manufactured using several techniques that, in some cases, do not allow full control over the size and orientation of the pores characterizing the scaffold. A novel hypothesis that a reaction–diffusion (RD) system can be used for designing the geometrical specifications of the bone matrix is thus presented here. The hypothesis was evaluated by making simulations in two- and three-dimensional RD systems in conjunction with the biomaterial scaffold. The results showed the methodology's effectiveness in controlling features such as the percentage of porosity, size, orientation, and interconnectivity of pores in an injectable bone matrix produced by the proposed hypothesis.


2009 ◽  
Vol 29 (11) ◽  
pp. 3173-3185 ◽  
Author(s):  
André Kleinridders ◽  
Hans-Martin Pogoda ◽  
Sigrid Irlenbusch ◽  
Neil Smyth ◽  
Csaba Koncz ◽  
...  

ABSTRACT PLRG1, an evolutionarily conserved component of the spliceosome, forms a complex with Pso4/SNEV/Prp19 and the cell division and cycle 5 homolog (CDC5L) that is involved in both pre-mRNA splicing and DNA repair. Here, we show that the inactivation of PLRG1 in mice results in embryonic lethality at 1.5 days postfertilization. Studies of heart- and neuron-specific PLRG1 knockout mice further reveal an essential role of PLRG1 in adult tissue homeostasis and the suppression of apoptosis. PLRG1-deficient mouse embryonic fibroblasts (MEFs) fail to progress through S phase upon serum stimulation and exhibit increased rates of apoptosis. PLRG1 deficiency causes enhanced p53 phosphorylation and stabilization in the presence of increased γ-H2AX immunoreactivity as an indicator of an activated DNA damage response. p53 downregulation rescues lethality in both PLRG1-deficient MEFs and zebrafish in vivo, showing that apoptosis resulting from PLRG1 deficiency is p53 dependent. Moreover, the deletion of PLRG1 results in the relocation of its interaction partner CDC5L from the nucleus to the cytoplasm without general alterations in pre-mRNA splicing. Taken together, the results of this study identify PLRG1 as a critical nuclear regulator of p53-dependent cell cycle progression and apoptosis during both embryonic development and adult tissue homeostasis.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Michael Zenzes ◽  
Paul Zaslansky

AbstractMicro-CT provides critical data for musculoskeletal research, yielding three-dimensional datasets containing distributions of mineral density. Using high-resolution scans, we quantified changes in the fine architecture of bone in the spine of young mice. This data is made available as a reference to physiological cancellous bone growth. The scans (n = 19) depict the extensive structural changes typical for female C57BL/6 mice pups, aged 1-, 3-, 7-, 10- and 14-days post-partum, as they attain the mature geometry. We reveal the micro-morphology down to individual trabeculae in the spine that follow phases of mineral-tissue rearrangement in the growing lumbar vertebra on a micrometer length scale. Phantom data is provided to facilitate mineral density calibration. Conventional histomorphometry matched with our micro-CT data on selected samples confirms the validity and accuracy of our 3D scans. The data may thus serve as a reference for modeling normal bone growth and can be used to benchmark other experiments assessing the effects of biomaterials, tissue growth, healing, and regeneration.


2021 ◽  
pp. 108128652110258
Author(s):  
Yi-Ying Feng ◽  
Xiao-Jun Yang ◽  
Jian-Gen Liu ◽  
Zhan-Qing Chen

The general fractional operator shows its great predominance in the construction of constitutive model owing to its agility in choosing the embedded parameters. A generalized fractional viscoelastic–plastic constitutive model with the sense of the k-Hilfer–Prabhakar ( k-H-P) fractional operator, which has the character recovering the known classical models from the proposed model, is established in this article. In order to describe the damage in the creep process, a time-varying elastic element [Formula: see text] is used in the proposed model with better representation of accelerated creep stage. According to the theory of the kinematics of deformation and the Laplace transform, the creep constitutive equation and the strain of the modified model are established and obtained. The validity and rationality of the proposed model are identified by fitting with the experimental data. Finally, the influences of the fractional derivative order [Formula: see text] and parameter k on the creep process are investigated through the sensitivity analyses with two- and three-dimensional plots.


2002 ◽  
Vol 124 (4) ◽  
pp. 953-957 ◽  
Author(s):  
D. Lornage ◽  
E. Chatelet ◽  
G. Jacquet-Richardet

Rotating parts of turbomachines are generally studied using different uncoupled approaches. For example, the dynamic behavior of shafts and wheels are considered independently and the influence of the surrounding fluid is often taken into account in an approximate way. These approaches, while often sufficiently accurate, are questionable when wheel-shaft coupling is observed or when fluid elements are strongly coupled with local structural deformations (leakage flow between wheel and casing, fluid bearings mounted on a thin-walled shaft, etc.). The approach proposed is a step toward a global model of shaft lines. The whole flexible wheel-shaft assembly and the influence of specific fluid film elements are considered in a fully three-dimensional model. In this paper, the proposed model is first presented and then applied to a simple disk-shaft assembly coupled with a fluid film clustered between the disk and a rigid casing. The finite element method is used together with a modal reduction for the structural analysis. As thin fluid films are considered, the Reynolds equation is solved using finite differences in order to obtain the pressure field. Data are transferred between structural and fluid meshes using a general method based on an interfacing grid concept. The equations governing the whole system are solved within a time-marching procedure. The results obtained show significant influence of specific three-dimensional features such as disk-shaft coupling and local disk deformations on global behavior.


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