A shape-driven reentrant jamming transition in confluent monolayers of synthetic cell-mimics (2401.13437v1)

Abstract: Many critical biological processes, like wound healing, require confluent cell monolayers/bulk tissues to transition from a jammed solid-like to a fluid-like state. Although numerical studies anticipate changes in the cell shape alone can lead to unjamming, experimental support for this prediction is not definitive because, in living systems, fluidization due to density changes cannot be ruled out. Additionally, a cell's ability to modulate its motility only compounds difficulties since even in assemblies of rigid active particles, changing the nature of self-propulsion has non-trivial effects on the dynamics. Here, we design and assemble a monolayer of synthetic cell-mimics and examine their collective behaviour. By systematically increasing the persistence time of self-propulsion, we discovered a cell shape-driven, density-independent, re-entrant jamming transition. Notably, we observed cell shape and shape variability were mutually constrained in the confluent limit and followed the same universal scaling as that observed in confluent epithelia. Dynamical heterogeneities, however, did not conform to this scaling, with the fast cells showing suppressed shape variability, which our simulations revealed is due to a transient confinement effect of these cells by their slower neighbors. Our experiments unequivocally establish a morphodynamic link, demonstrating that geometric constraints alone can dictate epithelial jamming/unjamming.

• The paper demonstrates that geometric shape changes trigger reentrant jamming transitions in synthetic cell-mimics.
• It employs flexible paper-ring cell-mimics with tunable activity to validate theoretical predictions of density-independent unjamming.
• Findings reveal that cell geometry and persistence time modulate collective dynamics, offering insights for tissue mechanics and pathology.

Review of "A shape-driven reentrant jamming transition in confluent monolayers of synthetic cell-mimics"

The paper "A shape-driven reentrant jamming transition in confluent monolayers of synthetic cell-mimics" explores the dynamics of cell-mimicking structures designed to emulate the behavior of confluent epithelia, particularly focusing on jamming and unjamming transitions driven by geometric constraints. This paper is significant for its experimental validation of theoretical predictions of a shape-driven, density-independent jamming transition in cellular assemblies.

The authors investigate the collective behavior of synthetic cell-mimics—flexible paper rings enclosing active elliptical particles—under varying conditions of activity persistence time and packing density. The cell-mimics were carefully designed to provide two main features: deformability and tunable activity, enabling systematic studies not feasible with living cells due to biological variability and uncontrollable parameters. The cell-mimics displayed a marked capacity for shape-driven unjamming, independent of density changes, a breakthrough finding that highlights the role of cell geometry in dictating the dynamics of cellular assemblies.

Numerical studies and experiments have long suggested that cell shape changes could independently drive unjamming transitions, but experimental support has been clouded by factors such as cell density fluctuations and self-motility modulation. By successfully controlling these variables in a synthetic model, the authors establish a compelling morphodynamic link governing epithelial jamming and unjamming mechanisms. This is evident in their discovery of a reentrant jamming transition mediated by cell shape alterations, visible prominently near confluence at specific ranges of persistence time and aspect ratio variability.

The reentrant behavior observed implies that beyond a threshold, increased activity persistence time leads to enhanced cell-cell interactions, resulting in renewed jamming despite significant individual cell motility. Notably, shape variability followed a universal scaling law observed in biological tissues, confirming the theoretical models and predictions of cell dynamics and structure interdependence. However, discrepancies at the local level, such as reduced shape variability among fast-moving cells due to transient confinement by slower neighbors, warrant further examination, as highlighted by the simulations using Vertex and Cellular Potts models.

This research presents significant theoretical and practical implications. Theoretically, it solidifies the concept of geometry-dictated jamming and unjamming in cell collectives, advancing our understanding of tissue dynamics. Practically, the synthetic model system's ability to fine-tune key physical parameters promotes its potential application in disentangling complex cellular processes and behaviors in developmental biology and pathology, such as epithelial organization and cancer metastasis. Additionally, the model offers avenues for future explorations into other factors like intercellular friction and environmental interactions, further solidifying the framework of context-dependent cellular mechanics.

Future research may expand on the findings here by exploiting the tunability offered by synthetic cell-mimics to investigate heterogeneous cell properties' impact on collective behavior. Intriguing questions remain, specifically concerning how tunable heterogeneity in cell properties influences cellular sorting and functional organization, a crucial aspect of tissue engineering and regenerative medicine.

In conclusion, this paper provides a significant contribution to the understanding of confluent epithelial systems, offering compelling evidence of the geometric influences on jamming transitions. It opens pathways for advancing both theoretical models and experimental methods, enhancing our capability to mimic and paper complex biological systems with extraordinary precision.