Abnormal Aggregation of Invasive Cancer Cells Induced by Collective Polarization and ECM-Mediated Mechanical Coupling in Coculture Systems

Xiaochen Wang; Shaohua Chen; Hanqing Nan; Ruchuan Liu; Yu Ding; Kena Song; Jianwei Shuai; Qihui Fan; Yu Zheng; Fangfu Ye; Yang Jiao; Liyu Liu

doi:10.34133/2021/9893131

Abnormal Aggregation of Invasive Cancer Cells Induced by Collective Polarization and ECM-Mediated Mechanical Coupling in Coculture Systems

Research (Wash D C). 2021 Dec 8:2021:9893131. doi: 10.34133/2021/9893131. eCollection 2021.

Authors

Xiaochen Wang^{1

2

3

4}, Shaohua Chen⁵, Hanqing Nan⁵, Ruchuan Liu⁶, Yu Ding^{1

2}, Kena Song⁶, Jianwei Shuai⁷, Qihui Fan¹, Yu Zheng⁸, Fangfu Ye^{1

2

3

4}, Yang Jiao^{5

8}, Liyu Liu^{4

6}

Affiliations

¹ Beijing National Laboratory for Condensed Matte Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.
² School of Physical Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
³ Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325000, China.
⁴ Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325001, China.
⁵ Materials Science and Engineering, Arizona State University, Tempe, Arizona 85287, USA.
⁶ Chongqing Key Laboratory of Soft Condensed Matter Physics and Smart Materials, College of Physics, Chongqing University, Chongqing 401331, China.
⁷ Department of Physics, Xiamen University, Xiamen 361005, China.
⁸ Department of Physics, Arizona State University, Tempe, Arizona 85287, USA.

Abstract

Studies on pattern formation in coculture cell systems can provide insights into many physiological and pathological processes. Here, we investigate how the extracellular matrix (ECM) may influence the patterning in coculture systems. The model coculture system we use is composed of highly motile invasive breast cancer cells, initially mixed with inert nonmetastatic cells on a 2D substrate and covered with a Matrigel layer introduced to mimic ECM. We observe that the invasive cells exhibit persistent centripetal motion and yield abnormal aggregation, rather than random spreading, due to a "collective pulling" effect resulting from ECM-mediated transmission of active contractile forces generated by the polarized migration of the invasive cells along the vertical direction. The mechanism we report may open a new window for the understanding of biological processes that involve multiple types of cells.