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

Abstract

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.

Enhanced Piezoelectric Fibered Extracellular Matrix to Promote Cardiomyocyte Maturation and Tissue Formation: A 3D Computational Model

“…Moreover, due to the movement of the cell on a viscous ECM, we consider the effect of the drag force. As the drag force, F drag , is proportional to the cell velocity, v, and the ECM viscosity, η, it can be defined by [49,56]…”

“…To describe cell maturation, we define t mat (γ c , t) as the time necessary by a cell to maturate and trigger cell processes such as differentiation and proliferation. Thus, t mat (γ c , t) can be determined by [51,56]…”

“…As the cells interact with the ECM, it is necessary to define the state of maturation of the cell, which is related to the cell-cycle evolution [78]. For this purpose, a Maturation Index (MI) is defined as cell-cycle completed time, which is calculated as [51,56]…”

Skin Mechanobiology and Biomechanics: From Homeostasis to Wound Healing

“…Mechanosensing is then followed by the process of mechanotransduction that occurs through alterations at the subcellular and molecular levels through intracellular proteins (e.g., vinculin and talin), kinases and phosphatases (e.g., focal adhesion kinase (FAK)), cytoskeletal components (i.e., actin filament and microtubule), or intermediate filaments (e.g., keratin, dermin, plectin, lamin, and vimentin) [93]. Thus it is clear why the mechanosensing force is mechanotransduced into a biological response related with the activated signaling pathway that can be, for instance, adhesion, survival, apoptosis, proliferation, migration, or differentiation [93,96,97].…”

Patient-specific stress analyses in the ascending thoracic aorta using a finite-element implementation of the constrained mixture theory

“…The proposed model is implemented within the commercial FE software Abaqus [23] through a coupled user material subroutine (UMAT) [16,38]. A 3D structural mesh made of hexahedral elements with eight nodes and eight Gauss points is reconstructed across the wall of the artery.…”