Supplementary MaterialsSupplementary Information srep40639-s1. are optimally adjusted by using the available data from the experiment with adipose-derived stem cells subjected to the application of cyclic uniaxial strains of the magnitude of 10%. The modeling results predict the kinetics of the process of Mouse monoclonal to HA Tag. HA Tag Mouse mAb is part of the series of Tag antibodies, the excellent quality in the research. HA Tag antibody is a highly sensitive and affinity monoclonal antibody applicable to HA Tagged fusion protein detection. HA Tag antibody can detect HA Tags in internal, Cterminal, or Nterminal recombinant proteins. myogenic differentiation, including the number of cells in each stage of differentiation and the rates of differentiation from one stage to another Clozapine N-oxide pontent inhibitor for different strains from 4% to 16%. The developed model can help better understand the process of myogenic differentiation and the effects of mechanical cues on stem cell use in muscle therapies. Effective models have recently been proposed for a variety of cells under different conditions where mechanical factors are involved. They include analyses of spreading on patterned substrates1, alignment under cyclic load2,3, mechanotransduction under applied shear forces4, deformation under 3-D flow forces5, force generation with 3-D tissue6, etc. However, the modeling of stem cell mechanobiology, where mechanotransduction converges with cell differentiation, remains less developed. For stem cell differentiation, the mechanical factors are of primary importance because they transform into cells where such factors are part of the cell microenvironment7,8,9,10. Moreover, it has been recognized that factors such as cell area11 substrate stiffness12, extracellular matrix (ECM) viscoelasticity13, and surface topography14,15 can be used as tools to direct and optimize stem cell differentiation. A number of stem cells, including satellite cells16, bone marrow stem cells17, and induced pluripotent stem Clozapine N-oxide pontent inhibitor cells18, have shown a potential for skeletal muscle treatment. One promising approach is related to adipose-derived stem cells (ASCs) because they are abundant and easily accessible in the body of a patient19. The mechanical factors can significantly affect ASC myogenesis20. Huri em et al /em . have recently shown that the application of strains to the myogenic environment significantly enhances the outcome of ASC differentiation21,22. To better understand this effect on stem cell myogenesis, we have proposed a phenomenological model23 where the strain effect was incorporated through the experimental data of Huri em et al /em .22 for the static (no applied strains) and dynamic (strain magnitude of 10%) cases. However, the biological mechanisms of the strain effect and stem cell differentiation remained to be further developed. In the present paper, we consider stem cell myogenesis and focus on its differentiation part (Fig. 1a) as well as around the mechanism of the strain effect. We add a transcription factor, myogenin, into consideration and model the late factors, MyoD, myogenin, and MHC, as a transcription network. We interpret the strain effect via a strain-generated signaling molecule that affects the transcriptional activity of the MyoD and myogenin factors (Fig. 1b). As a result, the transcription factors and the applied strain enter the model via saturating Michaelis-Menten functions instead of linear functions in our previous model23. Finally, we decided the optimal differentiation parameters of the model by fitting the available experimental data for ACSs subjected to the strain of 10% magnitude22 and predict the differentiation kinetics for different strains. Open in a separate window Physique 1 Conceptual model of stem cell myogenesis.(a) Six stages and the expression of myogenic factors. The first three Clozapine N-oxide pontent inhibitor stages occur via asymmetric cell division, and the latest three stages (shown within the dashed line) proceed through direct differentiation. The multi-stage process of stem cell myogenesis is usually affected by external signaling from the myogenic medium, extracellular matrix (strain effect), and cell-cell conversation if a cell density threshold is usually reached. (b) The proposed mechanism of stem cell myogenic differentiation associated with the conversation among the transcription factors, MyoD and myogenin, and the late myogenic factor, MHC. The strain effect is usually interpreted as strain-generated signaling molecule, S, that affects the transcriptional activity of MyoD and myogenin. Results Model of stem.