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PANC-1 Migration And Cluster Formation Is A Result Of Random Migration

Holfinger, Steven James

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2011, Master of Science, Ohio State University, Biomedical Engineering.
Islet cell transplantation has already shown improved control of glucose levels and the potential to achieve insulin independence in type 1 diabetes mellitus; however there is a shortage of organ donors needed to match patient needs. In the search for alternative sources of islets, many cell types have shown signs of beta cell differentiation by secreting c-peptide, insulin, and glucagon. When maintained in serum-free medium, human epithelial-like pancreatic adenocarcinoma (PANC-1) cells go through a morphological transition and cluster. These islet-like cell aggregates subsequently express glucagon, somatostatin, and insulin, indicating that clustering may play an important role in differentiation towards beta cells. Little is known about how these specific cells coordinate their movement to form multi-cellular structures, however cells could migrate towards one another through intracellular long range signaling, or they could randomly migrate until short range interactions hold them together. Here, we use time lapse microscopy to follow PANC-1 cells for 24 hours to determine how cells migrate when forming clusters. In order to determine if isolated cells move towards regions of higher cell density, a cluster that was pre-formed using the hanging drop method was dropped on a sub confluent monolayer. The total distance that cells travelled in a certain direction relative to the cluster indicated that there was no preferential movement in any direction, including towards the cluster. The average distance a cell moves towards or away from the cluster in relation to the distance between the cell and the cluster also indicated that there was no preferential movement towards the cluster, regardless of the distance a cell was from the cluster. The average speed a cell moves in relation to the cluster also does not indicate that there is directed migration, nor does the average value for the chemotactic index or the average value for directionality. Fluid convection was used in an attempt to decouple clustering and soluble concentration gradients. Samples that were on a rocker had significantly larger clusters formed after 24 hours compared to similar samples that were kept stationary in the same incubator. Additionally, rules for an agent based modeling approach are presented that could lead to cluster formation based on random migration and short range interactions alone. These experiments were all carried out to determine the role of either short range interactions, coupled with cell motility based on random walks, or long range interactions, coupled with directed cell motion towards areas of higher cell density, is the mechanism behind PANC-1 clustering.
Keith Gooch (Advisor)
Samir Ghadiali (Committee Member)
70 p.

Recommended Citations

Citations

  • Holfinger, S. J. (2011). PANC-1 Migration And Cluster Formation Is A Result Of Random Migration [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1308332896

    APA Style (7th edition)

  • Holfinger, Steven. PANC-1 Migration And Cluster Formation Is A Result Of Random Migration. 2011. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1308332896.

    MLA Style (8th edition)

  • Holfinger, Steven. "PANC-1 Migration And Cluster Formation Is A Result Of Random Migration." Master's thesis, Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1308332896

    Chicago Manual of Style (17th edition)