Dynamic intracellular mechanical cues facilitate collective signaling responses

Bingchen Che; Wei Zhao; Yanan Liu; Dan Sun; Guangyin Jing; Jintao Bai; Xiqiao Feng; Ce Zhang

doi:10.1016/j.isci.2021.102396

Dynamic intracellular mechanical cues facilitate collective signaling responses

iScience. 2021 Apr 3;24(5):102396. doi: 10.1016/j.isci.2021.102396. eCollection 2021 May 21.

Authors

Bingchen Che¹, Wei Zhao¹, Yanan Liu², Dan Sun¹, Guangyin Jing², Jintao Bai¹, Xiqiao Feng³, Ce Zhang¹

Affiliations

¹ State Key Laboratory of Photon-Technology in Western China Energy, Institute of Photonics and Photon-Technology, Northwest University, Xi'an 710069, China.
² School of Physics, Northwest University, Xi'an 710069, China.
³ Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, Beijing 100084, China.

Abstract

Collective behavior emerges in diverse life machineries, e.g., the immune responses to dynamic stimulations. The essential questions that arise here are that whether and how cells in vivo collectively respond to stimulation frequencies higher than their intrinsic natural values, e.g., the acute inflammation conditions. In this work, we systematically studied morphological and signaling responses of population fibroblasts in an interconnected cell monolayer and uncovered that, besides the natural NF-κB oscillation frequency of 1/90 min^-1, collective signaling response emerges in the cell monolayer at 1/20 min^-1 TNF-α input periodicity as well. Using a customized microfluidic device, we independently induced dynamic chemical stimulation and cytoskeleton reorganization on the stand-alone cells to exclude the effect of cell-cell communication. Our results reveal that, at this particular frequency, chemical stimulation is translated into dynamic intracellular mechanical cues through RAC1-medicated induction of dynamic cell-cell connections and cytoskeleton reorganizations, which synergize with chemical input to facilitate collective signaling responses.

Keywords: Cell Biology; Cellular Physiology; Mechanobiology.