Modeling and simulation of cell populations interaction

2020

Comput Mech

The processes in which cardiac cells are reorganized for tissue regeneration is still unclear. It is a complicated process that is orchestrated by many factors such as mechanical, chemical, thermal, and/or electrical cues. Studying and optimizing these conditions in-vitro is complicated and time costly. In such cases, in-silico numerical simulations can offer a reliable solution to predict and optimize the considered conditions for the cell culture process. For this aim, a 3D novel and enhanced numerical model has been developed to study the effect of the mechanical properties of the extracellular matrix (ECM) as well as the applied external forces in the process of the cell differentiation and proliferation for cardiac muscle tissue regeneration. The model has into account the essential cellular processes such as migration, cell-cell interaction, cell-ECM interaction, differentiation, proliferation and/or apoptosis. It has employed to study the initial stages of cardiac muscle tissue formation within a wide range of ECM stiffness (8-50 kPa). The results show that, after cell culture within a free surface ECM, cells tend to form elongated aggregations in the ECM center. The formation rate, as well as the aggregation morphology, have been found to be a function of the ECM stiffness and the applied external force. Besides, it has been found that the optimum ECM stiffness for cardiovascular tissue regeneration is in the range of 29-39 kPa, combined with the application of a mechanical stimulus equivalent to deformations of 20-25%.

Section: Cell Fatementioning

confidence: 99%

Mechanical stimulation of cell microenvironment for cardiac muscle tissue regeneration: a 3D in-silico model

Urdeitx

2020

Comput Mech

“…In normal tissues, this generally refers to cells that replenish the tissue by cell growth followed by cell division. Cell proliferation occurs in defined steps including the first growth phase, the synthesis phase, the second growth phase and the mitosis phase, respectively [ 48 , 49 ]. During the first growth phase, known as the G1 phase, the cell synthesizes a huge content of biological material.…”

Section: Model Formulationmentioning

confidence: 99%

“…Subsequently, reorganization of the cell chromosomes is followed by the cell division so that a mother cell is divided into two daughter cells. This is a critical instant because some cells temporarily stop proliferation by entering into the quiescence state which is called the G0 phase [ 48 , 49 ].…”

Section: Model Formulationmentioning

confidence: 99%

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

Mousavi

2015

PLoS ONE

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.

“…Cell proliferation is the process of generating two daughter cells from a single mother. It occurs in four defined steps comprising the first growth phase, the synthesis phase, the second growth phase and the mitosis phase, respectively [18,66]. During the first growth phase (G1) the cell synthesizes biological material in order to grow.…”

Section: Cell Differentiation Proliferation and Apoptosismentioning

confidence: 99%

“…Finally, cell division (cytokinesis) occurs and a mother cell is divided into two daughter cells in the mitosis phase (M). In this critical phase some cells may temporarily stop proliferation and enter into the quiescence state (G0) while others participate in the cycle of cell proliferation [18,66]. The main objective here is to model the proliferation process through a biologically proper environment.…”

Section: Cell Differentiation Proliferation and Apoptosismentioning

confidence: 99%

Numerical modeling of cell differentiation and proliferation in force-induced substrates via encapsulated magnetic nanoparticles

Mousavi

Computer Methods and Programs in Biomedicine

2016

Cell migration, differentiation, proliferation and apoptosis are the main processes in tissue regeneration. Mesenchymal Stem Cells (MSCs) have the potential to differentiate into many cell phenotypes such as tissue-or organ-specific cells to perform special functions. Experimental observations illustrate that differentiation and proliferation of these cells can be regulated according to internal forces induced within their Extracellular matrix (ECM). The process of how exactly they interpret and transduce these signals is not well understood. Therefore, a previously developed three-dimensional (3D) computational model is here extended and employed to study how force-free substrates (FFS) and force-induced substrate (FIS) control cell differentiation and/or proliferation during the mechanosensing process. Consistent with experimental observations, it is assumed that cell internal deformation (a mechanical signal) in correlation with the cell maturation state directly triggers cell differentiation and/or proliferation. ECM is modeled as Neo-Hookean hyperelastic material assuming that cells are cultured within 3D nonlinear hydrogels. In agreement with wellknown experimental observations, the findings here indicate that within neurogenic (0.1-1 kPa), chondrogenic (20-25 kPa) and osteogenic (30-45 kPa) substrates, MSC differentiation and cell proliferation can be precipitated by inducing the substrate with an internal force. Therefore, cells require a longer time to grow and maturate within force-free substrates than withen force-induced substrates. In the instance of MSC differentiation into a compatible phenotype, the magnitude of the net traction force increases within chondrogenic and osteogenic substrates while it reduces within neurogenic substrates. This is consistent with experimental studies and numerical works recently published by the same authors. However, in all cases the magnitude of the net traction force considerably increases at the instant of cell proliferation because of cell-cell interaction. Consequently, the present model provides new perspectives to delineate the role of force-induced substrates in remotely controlling the cell fate during cell-matrix interaction, which open the door for new tissue regeneration methodologies.