Abstract:Investigation of energy mechanisms at the collective cell scale is a challenge for understanding various biological processes, such as embryonic development and tumor metastasis. Here we investigate the energetics of self-sustained mesoscale turbulence in confluent two-dimensional (2D) cell monolayers. We find that the kinetic energy and enstrophy of collective cell flows in both epithelial and non-epithelial cell monolayers collapse to a family of probability density functions, which follow the q-Gaussian dis… Show more
“…In the jammed phase, each cell becomes virtually frozen in place, trapped by its immediate neighbors, in a collective phase where intercellular rearrangements are rare. Conversely, in the unjammed phase, intercellular rearrangements are frequent and the confluent cellular collective moves cooperatively, collectively, and vigorously in packs and swirls reminiscent of turbulent fluid flow (1,20,21).…”
Epithelial tissue can transition from a jammed, solid-like, quiescent phase to an unjammed, fluid-like, migratory phase, but the underlying molecular events of the unjamming transition (UJT) remain largely unexplored. Using primary human bronchial epithelial cells (HBECs) and one well-defined trigger of the UJT, compression mimicking the mechanical effects of bronchoconstriction, here, we combine RNA sequencing data with protein-protein interaction networks to provide the first genome-wide analysis of the UJT. Our results show that compression induces an early transcriptional activation of the membrane and actomyosin network and a delayed activation of the extracellular matrix (ECM) and cell-matrix networks. This response is associated with a signaling cascade that promotes actin polymerization and cellular motility through the coordinated interplay of downstream pathways including ERK, JNK, integrin signaling, and energy metabolism. Moreover, in nonasthmatic versus asthmatic HBECs, common genomic patterns associated with ECM remodeling suggest a molecular connection between airway remodeling, bronchoconstriction, and the UJT.
“…In the jammed phase, each cell becomes virtually frozen in place, trapped by its immediate neighbors, in a collective phase where intercellular rearrangements are rare. Conversely, in the unjammed phase, intercellular rearrangements are frequent and the confluent cellular collective moves cooperatively, collectively, and vigorously in packs and swirls reminiscent of turbulent fluid flow (1,20,21).…”
Epithelial tissue can transition from a jammed, solid-like, quiescent phase to an unjammed, fluid-like, migratory phase, but the underlying molecular events of the unjamming transition (UJT) remain largely unexplored. Using primary human bronchial epithelial cells (HBECs) and one well-defined trigger of the UJT, compression mimicking the mechanical effects of bronchoconstriction, here, we combine RNA sequencing data with protein-protein interaction networks to provide the first genome-wide analysis of the UJT. Our results show that compression induces an early transcriptional activation of the membrane and actomyosin network and a delayed activation of the extracellular matrix (ECM) and cell-matrix networks. This response is associated with a signaling cascade that promotes actin polymerization and cellular motility through the coordinated interplay of downstream pathways including ERK, JNK, integrin signaling, and energy metabolism. Moreover, in nonasthmatic versus asthmatic HBECs, common genomic patterns associated with ECM remodeling suggest a molecular connection between airway remodeling, bronchoconstriction, and the UJT.
“…Cells can also be used to manufacture NMMs. On the one hand, cell populations exhibit polarization and alignment [66,67], and the kinetic energy and enstrophy of cell monolayer collective flows obey q-Gaussian distribution [68]. These findings shed light on the potential biomedical applications of assembling cell-based NMMs.…”
Nano/micromotors (NMMs) are tiny objects capable of converting energy into mechanical motion. Recently, a wealth of active matter including synthetic colloids, cytoskeletons, bacteria, and cells have been used to construct NMMs. The self-sustained motion of active matter drives NMMs out of equilibrium, giving rise to rich dynamics and patterns. Alongside the spontaneous dynamics, external stimuli such as geometric confinements, light, magnetic field, and chemical potential are also harnessed to control the movements of NMMs, yielding new application paradigms of active matter. Here, we review the recent advances, both experimental and theoretical, in exploring biological NMMs. The unique dynamical features of collective NMMs are focused on, along with some possible applications of these intriguing systems.
“…In EMT, there is a complete loss of cell–cell adhesion and apical–basal polarity, with increased cellular motility, although partial EMT (pEMT) may occur with intermediate phenotypes ( Thiery, 2003 ; Mitchel et al, 2020 ). Although mesenchymal cells migrate as single cells solitary, epithelial plasticity can encompass other patterns of cellular movement as well, including collective motion ( Huang et al, 2015 ) resulting from what has been termed the unjamming transition (UJT) ( Mitchel et al, 2020 ; Park et al, 2016 ; O'Sullivan et al, 2020 ; Lin et al, 2021 ; Kim et al, 2020 , 2013 ). pEMT and cellular unjamming may both co-exist in response to stimuli ( Mitchel et al, 2020 ; O'Sullivan et al, 2020 ).…”
The airway epithelium is subjected to insults such as cigarette smoke (CS), a primary cause of Chronic Obstructive Pulmonary Disease (COPD) and serves as an excellent model to study cell plasticity. Both CS-exposed and COPD-patient derived epithelia (CHBE) display quantitative evidence of cellular plasticity, with loss of specialized apical features and a transcriptional profile suggestive of partial epithelial to mesenchymal transition, albeit with distinct cell motion indicative of cellular unjamming. These injured/diseased cells have an increased fraction of polymerized actin, due to loss of the actin-severing protein, cofilin-1. Decreasing polymerized actin restores the jammed state in both CHBE and CS exposed epithelia, indicating that the fraction of polymerized actin is critical in unjamming the epithelia. Kinetic energy spectral analysis suggests that loss of cofilin-1 results in unjamming, similar to that seen with both CS exposure and in CHBE cells. Our data suggest that in response to chronic injury, although epithelial cells display evidence of pEMT, their movement is more consistent with cellular unjamming. Inhibitors of actin polymerization rectify the unjamming features of the monolayer.
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