TY - JOUR
T1 - Incomplete Cell Sorting Creates Engineerable Structures with Long-Term Stability
AU - Tordoff, Jesse
AU - Krajnc, Matej
AU - Walczak, Nicholas
AU - Lima, Matthew
AU - Beal, Jacob
AU - Shvartsman, Stanislav
AU - Weiss, Ron
N1 - Funding Information:
This work has been supported by the Defense Advanced Research Projects Agency under contract no. W911NF-17-2-0098 . The views, opinions, and/or findings expressed are of the author(s) and should not be interpreted as representing the official views or policies of the US Department of Defense or the US government. This document does not contain technology or technical data controlled under either US International Traffic in Arms Regulation or US Export Administration Regulations.
Funding Information:
This work has been supported by the Defense Advanced Research Projects Agency under contract no. W911NF-17-2-0098. The views, opinions, and/or findings expressed are of the author(s) and should not be interpreted as representing the official views or policies of the US Department of Defense or the US government. This document does not contain technology or technical data controlled under either US International Traffic in Arms Regulation or US Export Administration Regulations. J.T. designed the experiments, set up the 3D aggregates, and performed the data analysis. J.T. and M.L. maintained and prepared the cell lines and performed the microscopy. N.W. and J.B. performed the image analysis and the data analysis. M.K. and S.S. created and analyzed the particle-based model. All of the authors wrote the manuscript and contributed to the interpretation and analysis of the results. The authors declare no competing interests.
Publisher Copyright:
© 2020 The Author(s)
PY - 2021/1/20
Y1 - 2021/1/20
N2 - Adhesion-mediated cell sorting has long been considered an organizing principle in developmental biology. While most computational models have emphasized the dynamics of segregation to fully sorted structures, cell sorting can also generate a plethora of transient, incompletely sorted states. The timescale of such states in experimental systems is unclear: if they are long-lived, they can be harnessed by development or engineered in synthetic tissues. Here, we use experiments and computational modeling to demonstrate how such structures can be systematically designed by quantitative control of cell composition. By varying the number of highly adhesive and less adhesive cells in multicellular aggregates, we find the cell-type ratio and total cell count control pattern formation, with resulting structures maintained for several days. Our work takes a step toward mapping the design space of self-assembling structures in development and provides guidance to the emerging field of shape engineering with synthetic biology.
AB - Adhesion-mediated cell sorting has long been considered an organizing principle in developmental biology. While most computational models have emphasized the dynamics of segregation to fully sorted structures, cell sorting can also generate a plethora of transient, incompletely sorted states. The timescale of such states in experimental systems is unclear: if they are long-lived, they can be harnessed by development or engineered in synthetic tissues. Here, we use experiments and computational modeling to demonstrate how such structures can be systematically designed by quantitative control of cell composition. By varying the number of highly adhesive and less adhesive cells in multicellular aggregates, we find the cell-type ratio and total cell count control pattern formation, with resulting structures maintained for several days. Our work takes a step toward mapping the design space of self-assembling structures in development and provides guidance to the emerging field of shape engineering with synthetic biology.
KW - cell sorting
KW - particle-based modeling
KW - self-organization
KW - synthetic biology
KW - synthetic morphogenesis
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U2 - 10.1016/j.xcrp.2020.100305
DO - 10.1016/j.xcrp.2020.100305
M3 - Article
AN - SCOPUS:85103128959
SN - 2666-3864
VL - 2
JO - Cell Reports Physical Science
JF - Cell Reports Physical Science
IS - 1
M1 - 100305
ER -