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

Background and objective Cell migration, differentiation, proliferation and apoptosis are the main processes in tissue regeneration. Mesenchymal Stem Cells 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. The process of how exactly they interpret and transduce these signals is not well understood. Methods A previously developed three-dimensional (3D) computational model is here extended and employed to study how force-free substrates and force-induced substrate 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. The Extracellular Matrix is modeled as Neo-Hookean hyperelastic material assuming that cells are cultured within 3D nonlinear hydrogels. Results In agreement with well-known experimental observations, the findings here indicate that within neurogenic (0.1–1 kPa), chondrogenic (20–25 kPa) and osteogenic (30–45 kPa) substrates, Mesenchymal Stem Cells differentiation and 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 within force-induced substrates. In the instance of Mesenchymal Stem Cells 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. Conclusions 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

Dense discrete phase model for tumor cell growth analysis in fluid environments

Cell-cell and cell-extracellular matrix interactions play a major role in tumor growth, which involves complex molecular intercommunications. We have developed a single-cell computational model in which fluid dynamics and cell-cell interaction are coupled to evaluate the growth of cancer cells in fluidic environments. The results demonstrate that, once the cell concentration increases, the cell-cell interaction increases, decreasing cell maturation time and increasing tumor growth rate

A computational model for cardiomyocytes mechano-electric stimulation to enhance cardiac tissue regeneration

Electrical and mechanical stimulations play a key role in cell biological processes, being essential in processes such as cardiac cell maturation, proliferation, migration, alignment, attachment, and organization of the contractile machinery. However, the mechanisms that trigger these processes are still elusive. The coupling of mechanical and electrical stimuli makes it difficult to abstract conclusions. In this sense, computational models can establish parametric assays with a low economic and time cost to determine the optimal conditions of in-vitro experiments. Here, a computational model has been developed, using the finite element method, to study cardiac cell maturation, proliferation, migration, alignment, and organization in 3D matrices, under mechano-electric stimulation. Different types of electric fields (continuous, pulsating, and alternating) in an intensity range of 50–350 Vm−1, and extracellular matrix with stiffnesses in the range of 10–40 kPa, are studied. In these experiments, the group’s morphology and cell orientation are compared to define the best conditions for cell culture. The obtained results are qualitatively consistent with the bibliography. The electric field orientates the cells and stimulates the formation of elongated groups. Group lengthening is observed when applying higher electric fields in lower stiffness extracellular matrix. Groups with higher aspect ratios can be obtained by electrical stimulation, with better results for alternating electric fields

Enhanced piezoelectric fibered extracellular matrix to promote cardiomyocyte maturation and tissue formation: a 3d computational model

Mechanical and electrical stimuli play a key role in tissue formation, guiding cell processes such as cell migration, differentiation, maturation, and apoptosis. Monitoring and controlling these stimuli on in vitro experiments is not straightforward due to the coupling of these different stimuli. In addition, active and reciprocal cell–cell and cell–extracellular matrix interactions are essential to be considered during formation of complex tissue such as myocardial tissue. In this sense, computational models can offer new perspectives and key information on the cell microenvironment. Thus, we present a new computational 3D model, based on the Finite Element Method, where a complex extracellular matrix with piezoelectric properties interacts with cardiac muscle cells during the first steps of tissue formation. This model includes collective behavior and cell processes such as cell migration, maturation, differentiation, proliferation, and apoptosis. The model has employed to study the initial stages of in vitro cardiac aggregate formation, considering cell–cell junctions, under different extracellular matrix configurations. Three different cases have been purposed to evaluate cell behavior in fibered, mechanically stimulated fibered, and mechanically stimulated piezoelectric fibered extra-cellular matrix. In this last case, the cells are guided by the coupling of mechanical and electrical stimuli. Accordingly, the obtained results show the formation of more elongated groups and enhancement in cell proliferation