SIMULATION OF STEM CELL DIFFERENTIATION IN NANOPATTERN BASED ON FOCAL ADHESION PHENOMENON

• Main Author: Zacky Fairuza, Achmad
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/73862
• Institution: Institut Teknologi Bandung

Research on stem cells has grown rapidly in the last decade. This advencement happens due to stem cells are predicted to be a sophisticated method in the field of regenerative medicine. Supported by the innovation in the manufacture of iPSC (induced Pluripotent Stem Cell), this research becomes easier to do by in vitro and in vivo method. Therefore, one of the aim for further research is to control the direction of differentiation of stem cells. If these abilities can be utilized properly, stem cells can be directed to differentiate into other cells as needed. In addition of using conversion factors, stem cell differentiation can be influenced by nano-topography at the site of cell attachment. The nano-topography is called nanopattern if it has a good arrangement. The differentiation caused by nanopattern is predicted to occur due to the phenomenon of focal adhesion, which is a condition when integrin proteins on the cell surface that act as receptors bind to ligands on the substrate or bind to integrin receptors on other cell surfaces. This process then generates a mechanical signal that is passed into the core of the cell thereby providing stimulus signal for the formation of the cytoskeleton. The shape of the cytoskeleton can determine the direction of stem cell differentiation. One of the characteristics that can be seen in the differentiation process are the shape and area of the cell spreading and the interactions between cells. Despite such technological developments, stem cell research is still considered expensive and growing less rapidly than expected. The solution that has been taken is to create simulations or models. This solution has produced several models such as gene regulatory network (GRN), machine learning, and mechanistic models that have helped in finding conversion factors of stem cell differentiation. However, there are very few simulations regarding the effect of nanopatterns on stem cell differentiation. For this reason, in this study, the authors created a 2D system to simulate the phenomenon of cell differentiation in nanopatterns. The purpose of this simulation program is to observe the effect of nanopatterns on stem cell shape over time. The shape of the stem cell also describes the shape of the cytoskeleton so that it can define the direction of stem cell differentiation. The program exploits the dynamics of free-moving integrin receptors and static ligands that act as nanopatterns. These integrins will then move to ligands or to other unbound cel iv integrins using the principles of molecular dynamics and agent-based models. If the integrin and the target object are close enough, an integrin-ligand or integrin- integrin complex is formed. As a result of this dynamics, the shape of the cell will be deformed so that the cell spreading is seen in a certain time interval. The program used 160 integrins for each cell. While the distance between the ligands compared to their size (d/????????????????) varied in the range of 6 to 16 as reported in previous studies. The results of the simulation system are compared with the experimental results to see qualitative similarities. In this research, tests were carried out to determine the effect of parameters in stem cell simulations on nanopatterns. Furthermore, by using parameters that have been obtained from previously reported research, variations of the distance of the nanopattern and the shape of the nanopattern are carried out on the area of cell dilation and its effect on interactions between cells. The results obtained show good agreement with observations in the experiment. The density of integrins in cells is also used as a model to describe the strength of the cytoskeleton formed. It is hoped that this simulation program can provide an overview of the physical mechanisms in the phenomenon of stem cell differentiation and help speed up the process of stem cell research. In addition, this simulation program can also reduce costs in making nanopatterns and the stem cells themselves