More Like this

1. Does nematic order allow groups of elongated cells to sense electric fields better?

   https://doi.org/10.1371/journal.pone.0325800  

   Kaiyrbekov, Kurmanbek; Camley, Brian A (June 2025, PLOS One)

   Sung, Baeckkyoung (Ed.)

   Collective response to external directional cues like electric fields helps guide tissue development, regeneration, and wound healing. In this study we focus on the impact of anisotropy in cell shape and local cell alignment on the collective response to electric fields. We model elongated cells that have a different accuracy sensing the field depending on their orientation with respect to the field. With this framework, we assume cells are better sensors if they can align their long axes perpendicular to the field. Elongated cells often line up with their long axes in the same direction — “nematic order” – does a nematic cell-cell interaction allow groups of cells to share information about their orientation to sense fields more accurately? We use simulations of a simple model to show that if cells orient themselves perpendicular to their average velocity, alignment of a cell’s long axis to its nearest neighbors’ orientation can in some circumstances enhance the directional response to electric fields. We also show that cell-cell adhesion modulates the accuracy of cells in the group. 

   more » « less
2. Fluctuations can induce local nematic order and extensile stress in monolayers of motile cells

   https://doi.org/10.1039/D0SM02027C  

   Vafa, Farzan; Bowick, Mark J.; Shraiman, Boris I.; Marchetti, M. Cristina (March 2021, Soft Matter)

   null (Ed.)

   Recent experiments in various cell types have shown that two-dimensional tissues often display local nematic order, with evidence of extensile stresses manifest in the dynamics of topological defects. Using a mesoscopic model where tissue flow is generated by fluctuating traction forces coupled to the nematic order parameter, we show that the resulting tissue dynamics can spontaneously produce local nematic order and an extensile internal stress. A key element of the model is the assumption that in the presence of local nematic alignment, cells preferentially crawl along the nematic axis, resulting in anisotropy of fluctuations. Our work shows that activity can drive either extensile or contractile stresses in tissue, depending on the relative strength of the contractility of the cortical cytoskeleton and tractions by cells on the extracellular matrix. 

   more » « less
3. Condensation tendency and planar isotropic actin gradient induce radial alignment in confined monolayers

   https://doi.org/10.7554/eLife.60381  

   Xie, Tianfa; St Pierre, Sarah R; Olaranont, Nonthakorn; Brown, Lauren E; Wu, Min; Sun, Yubing (September 2021, eLife)

   null (Ed.)

   A monolayer of highly motile cells can establish long-range orientational order, which can be explained by hydrodynamic theory of active gels and fluids. However, it is less clear how cell shape changes and rearrangement are governed when the monolayer is in mechanical equilibrium states when cell motility diminishes. In this work, we report that rat embryonic fibroblasts (REF), when confined in circular mesoscale patterns on rigid substrates, can transition from the spindle shapes to more compact morphologies. Cells align radially only at the pattern boundary when they are in the mechanical equilibrium. This radial alignment disappears when cell contractility or cell-cell adhesion is reduced. Unlike monolayers of spindle-like cells such as NIH-3T3 fibroblasts with minimal intercellular interactions or epithelial cells like Madin-Darby canine kidney (MDCK) with strong cortical actin network, confined REF monolayers present an actin gradient with isotropic meshwork, suggesting the existence of a stiffness gradient. In addition, the REF cells tend to condense on soft substrates, a collective cell behavior we refer to as the ‘condensation tendency’. This condensation tendency, together with geometrical confinement, induces tensile prestretch (i.e. an isotropic stretch that causes tissue to contract when released) to the confined monolayer. By developing a Voronoi-cell model, we demonstrate that the combined global tissue prestretch and cell stiffness differential between the inner and boundary cells can sufficiently define the cell radial alignment at the pattern boundary. 

   more » « less
4. Short-term bioelectric stimulation of collective cell migration in tissues reprograms long-term supracellular dynamics

   https://doi.org/10.1093/pnasnexus/pgac002  

   Wolf, Abraham_E; Heinrich, Matthew_A; Breinyn, Isaac_B; Zajdel, Tom_J; Cohen, Daniel_J; Levine, ed., Bruce_L (March 2022, PNAS Nexus)

   Abstract The ability to program collective cell migration can allow us to control critical multicellular processes in development, regenerative medicine, and invasive disease. However, while various technologies exist to make individual cells migrate, translating these tools to control myriad, collectively interacting cells within a single tissue poses many challenges. For instance, do cells within the same tissue interpret a global migration ‘command’ differently based on where they are in the tissue? Similarly, since no stimulus is permanent, what are the long-term effects of transient commands on collective cell dynamics? We investigate these questions by bioelectrically programming large epithelial tissues to globally migrate ‘rightward’ via electrotaxis. Tissues clearly developed distinct rear, middle, side, and front responses to a single global migration stimulus. Furthermore, at no point poststimulation did tissues return to their prestimulation behavior, instead equilibrating to a 3rd, new migratory state. These unique dynamics suggested that programmed migration resets tissue mechanical state, which was confirmed by transient chemical disruption of cell–cell junctions, analysis of strain wave propagation patterns, and quantification of cellular crowd dynamics. Overall, this work demonstrates how externally driving the collective migration of a tissue can reprogram baseline cell–cell interactions and collective dynamics, even well beyond the end of the global migratory cue, and emphasizes the importance of considering the supracellular context of tissues and other collectives when attempting to program crowd behaviors. 

   more » « less
5. Migration and division in cell monolayers on substrates with topological defects

   https://doi.org/10.1073/pnas.2301197120  

   Kaiyrbekov, Kurmanbek; Endresen, Kirsten; Sullivan, Kyle; Zheng, Zhaofei; Chen, Yun; Serra, Francesca; Camley, Brian A (July 2023, Proceedings of the National Academy of Sciences)

   Collective movement and organization of cell monolayers are important for wound healing and tissue development. Recent experiments highlighted the importance of liquid crystal order within these layers, suggesting that +1 topological defects have a role in organizing tissue morphogenesis. We study fibroblast organization, motion, and proliferation on a substrate with micron-sized ridges that induce +1 and −1 topological defects using simulation and experiment. We model cells as self-propelled deformable ellipses that interact via a Gay–Berne potential. Unlike earlier work on other cell types, we see that density variation near defects is not explained by collective migration. We propose instead that fibroblasts have different division rates depending on their area and aspect ratio. This model captures key features of our previous experiments: the alignment quality worsens at high cell density and, at the center of the +1 defects, cells can adopt either highly anisotropic or primarily isotropic morphologies. Experiments performed with different ridge heights confirm a prediction of this model: Suppressing migration across ridges promotes higher cell density at the +1 defect. Our work enables a mechanism for tissue patterning using topological defects without relying on cell migration. 

   more » « less