Dynamic self-organization of microwell-aggregated cellular mixtures.
Cells with different cohesive properties self-assemble in a spatiotemporal and context-dependent manner. Previous studies on cell self-organization mainly focused on the spontaneous structural development within a short period of time during which the cell numbers remained constant. However the effect of cell proliferation over time on the self-organization of cells is largely unexplored. Here, we studied the spatiotemporal dynamics of self-organization of a co-culture of MDA-MB-231 and MCF10A cells seeded in a well defined space (i.e. non-adherent microfabricated wells). When cell-growth was chemically inhibited, high cohesive MCF10A cells formed a core surrounded by low cohesive MDA-MB-231 cells on the periphery, consistent with the differential adhesion hypothesis (DAH). Interestingly, this aggregate morphology was completely inverted when the cells were free to grow. At an initial seeding ratio of 1 : 1 (MDA-MB-231 : MCF10A), the fast growing MCF10A cells segregated in the periphery while the slow growing MDA-MB-231 cells stayed in the core. Another morphology developed at an inequal seeding ratio (4 : 1), that is, the cell mixtures developed a side-by-side aggregate morphology. We conclude that the cell self-organization depends not only on the cell cohesive properties but also on the cell seeding ratio and proliferation. Furthermore, by taking advantage of the cell self-organization, we purified human embryonic stem cells-derived pancreatic progenitors (hESCs-PPs) from co-cultured feeder cells without using any additional tools or labels.
Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York 14853, USA. mm826@cornell.edu.
Wei
W
Song
Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York 14853, USA. mm826@cornell.edu and Department of Physics, North Carolina A&T State University, Greensboro, North Carolina 27411, USA.
Chih-Kuan
CK
Tung
Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York 14853, USA. mm826@cornell.edu.
Yen-Chun
YC
Lu
Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA.
Yehudah
Y
Pardo
Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York 14853, USA. mm826@cornell.edu.
Mingming
M
Wu
School of Physics and Astronomy, Rochester Institute of Technology, Rochester, New York 14623, USA.
Moumita
M
Das
Department of Surgery, Weill Medical College of Cornell University, New York City, New York 10065, USA.
Der-I
DI
Kao
Department of Surgery, Weill Medical College of Cornell University, New York City, New York 10065, USA.
Shuibing
S
Chen
Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York 14853, USA. mm826@cornell.edu.
Minglin
M
Ma
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D053595:Embryonic Stem Cells / Q000166:cytology; D006801:Humans; D010179:Pancreas / Q000166:cytology