|M.Sc Student||Abu Hattum Shada|
|Subject||Role of Cell Mechanics in Adipogenesis and Migration|
|Department||Department of Biomedical Engineering||Supervisors||Professor Daphne Weihs|
|Professor Amit Gefen|
|Full Thesis text|
During development of obesity, fat cells expand adipose (fat) tissues by either proliferation or differentiation. The proliferation activity starts when mesenchymal stem cells (in fat) commit to the fat cell lineage, thus becoming preadipocytes (fibroblast-like and still motile), and given the appropriate conditions those differentiate into fat cells - adipocytes. Prior to differentiation, the preadipocytes may migrate in the tissues, can proliferate, and finally differentiate into new mature adipocytes, to increase the storage capacity of triglycerides in the tissue. Preadipocyte cell migration plays an important role in wound healing and tissue remodeling and regeneration. The morphology of the cells changes during differentiation from an elongated spindle-shape preadipocyte into a more rounded, differentiated adipocyte. That change allows efficient packing of spheroidal lipid droplets in the cells, but eliminates their ability to proliferate or migrate. The change in preadipocyte morphology had previously been shown. However, little is known about the dynamics, mechanical interactions of the cells with their microenvironment, and specifically the forces applied by the preadipocytes during migration and throughout the differentiation process in association with the morphological changes.
Accordingly, in this study, we evaluated changes in the morphology concurrently with the magnitude and location of traction forces applied by single cells onto a synthetic polyacrylamide (PAM) gel with stiffness of 2.4 kPa as animal abdominal and subcutaneous fat stiffness ranges between 0.3-3 kPa. In addition, we have evaluated structural and force application changes by individual preadipocytes during migration, which can serve as a basis for evaluation of wound healing and tissue remodeling in adipose-rich tissues. We found that preadipocytes applied forces that were concentrated at the poles of the cell, yet during differentiation the forces became more uniformly distributed around the cell perimeter. We observed that the total traction force per cell area is preserved during differentiation process, and identified a correlation between the changing cell morphology and the applied traction forces. The analysis of the migration of preadipocytes revealed that the cell movement is naturally non-directional, yet the cells’ orientation on the gel was aligned with the orientation of principal traction that they applied. In summary, in this work we focused on the mechanical behavior of preadipocytes and differentiating adipocytes in order to gain an understanding of the process of adipogenesis, and possibly control it.