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Role of Mechanical Cues in Cell Differentiation and Proliferation: A 3D Numerical Model.

ABSTRACT: Cell differentiation, proliferation and migration are essential processes in tissue regeneration. Experimental evidence confirms that cell differentiation or proliferation can be regulated according to the extracellular matrix stiffness. For instance, mesenchymal stem cells (MSCs) can differentiate to neuroblast, chondrocyte or osteoblast within matrices mimicking the stiffness of their native substrate. However, the precise mechanisms by which the substrate stiffness governs cell differentiation or proliferation are not well known. Therefore, a mechano-sensing computational model is here developed to elucidate how substrate stiffness regulates cell differentiation and/or proliferation during cell migration. In agreement with experimental observations, it is assumed that internal deformation of the cell (a mechanical signal) together with the cell maturation state directly coordinates cell differentiation and/or proliferation. Our findings indicate that MSC differentiation to neurogenic, chondrogenic or osteogenic lineage specifications occurs within soft (0.1-1 kPa), intermediate (20-25 kPa) or hard (30-45 kPa) substrates, respectively. These results are consistent with well-known experimental observations. Remarkably, when a MSC differentiate to a compatible phenotype, the average net traction force depends on the substrate stiffness in such a way that it might increase in intermediate and hard substrates but it would reduce in a soft matrix. However, in all cases the average net traction force considerably increases at the instant of cell proliferation because of cell-cell interaction. Moreover cell differentiation and proliferation accelerate with increasing substrate stiffness due to the decrease in the cell maturation time. Thus, the model provides insights to explain the hypothesis that substrate stiffness plays a key role in regulating cell fate during mechanotaxis.

SUBMITTER: Mousavi SJ

PROVIDER: S-EPMC4416758 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Mechanical metamaterials are man-made rationally-designed structures that present unprecedented mechanical properties not found in nature. One of the most well-known mechanical metamaterials is auxetics, which demonstrates negative Poisson's ratio (NPR) behavior that is very beneficial in several industrial applications. In this study, a specific type of auxetic metamaterial structure namely idealized 3D re-entrant structure is studied analytically, numerically, and experimentally. The noted structure is constructed of three types of struts-one loaded purely axially and two loaded simultaneously flexurally and axially, which are inclined and are spatially defined by angles θ and φ. Analytical relationships for elastic modulus, yield stress, and Poisson's ratio of the 3D re-entrant unit cell are derived based on two well-known beam theories namely Euler-Bernoulli and Timoshenko. Moreover, two finite element approaches one based on beam elements and one based on volumetric elements are implemented. Furthermore, several specimens are additively manufactured (3D printed) and tested under compression. The analytical results had good agreement with the experimental results on the one hand and the volumetric finite element model results on the other hand. Moreover, the effect of various geometrical parameters on the mechanical properties of the structure was studied, and the results demonstrated that angle θ (related to tension-dominated struts) has the highest influence on the sign of Poisson's ratio and its extent, while angle φ (related to compression-dominated struts) has the lowest influence on the Poisson's ratio. Nevertheless, the compression-dominated struts (defined by angle φ) provide strength and stiffness for the structure. The results also demonstrated that the structure could have zero Poisson's ratio for a specific range of θ and φ angles. Finally, a lightened 3D re-entrant structure is introduced, and its results are compared to those of the idealized 3D re-entrant structure.

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Role of Mechanical Cues in Cell Differentiation and Proliferation: A 3D Numerical Model.

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