Cells in tissues can organize into a broad spectrum of structures according to their function. Drastic changes of organization, such as epithelial-mesenchymal transitions or the formation of spheroidal aggregates, are often associated either to tissue morphogenesis or to cancer progression. Here, we study the organization of cell colonies by means of simulations of self-propelled particles with generic cell-like interactions. The interplay between cell softness, cell-cell adhesion, and contact inhibition of locomotion (CIL) yields structures and collective dynamics observed in several existing tissue phenotypes. These include regular distributions of cells, dynamic cell clusters, gel-like networks, collectively migrating monolayers, and 3D aggregates. We give analytical predictions for transitions between noncohesive, cohesive, and 3D cell arrangements. We explicitly show how CIL yields an effective repulsion that promotes cell dispersal, thereby hindering the formation of cohesive tissues. Yet, in continuous monolayers, CIL leads to collective cell motion, ensures tensile intercellular stresses, and opposes cell extrusion. Thus, our work highlights the prominent role of CIL in determining the emergent structures and dynamics of cell colonies.self-propelled particles | cell-cell adhesion | contact inhibition of locomotion | cell monolayers | collective motion C ell colonies exhibit a broad range of phenotypes. In terms of structure, collections of cells can arrange into distributions of single cells, assemble into continuous monolayers or multilayered tissues, or even form 3D agglomerates. In terms of dynamics, cell motility may simply be absent or produce random, directed, or collective migration of cells. Transitions between these states of tissue organization are characteristic of morphogenetic events and are also central to tumor formation and dispersal (1-4). Therefore, a physical understanding of the collective behavior of cell colonies will shed light on the regulation of many multicellular processes involved in development and disease.However, a complete physical picture of multicellular organization is not yet available, partly due to the challenge of modeling the complex interactions between cells. Here, we address this problem by means of large-scale simulations of self-propelled particles (SPP) endowed with interactions capturing generic cellular behaviors. Models of SPP with aligning interactions have been used to investigate collective cell motions in tissue monolayers (5-18). We extend this approach to unveil how the different structures and collective dynamics of cell colonies emerge from cell-cell interactions.In addition to an excluded-volume repulsion, cells generally feature a short-range attraction as a consequence of their active cortical contractility transmitted through cell-cell junctions. With no additional interactions, this attraction would typically lead to cohesive tissues. However, not all cell types form cohesive tissues. Whereas epithelial cells tend to form continuous monolayers...
We show how to extend the concept of heat capacity to nonequilibrium systems.The main idea is to consider the excess heat released by an already dissipative system when slowly changing the environment temperature. We take the framework of Markov jump processes to embed the specific physics of small driven systems and we demonstrate that heat capacities can be consistently defined in the quasistatic limit.Away from thermal equilibrium, an additional term appears to the usual energytemperature response at constant volume, explicitly in terms of the excess work. In linear order around an equilibrium dynamics that extra term is an energy-driving response and it is entirely determined from local detailed balance. Examples illustrate how the steady heat capacity can become negative when far from equilibrium. * Electronic address: eliran.boksenbojm@fys.kuleuven.be
We consider a cell as an elastic, contractile shell surrounding a liquid incompressible cytoplasm and with nonspecific adhesion. We perform numerical simulations of this model to study the mechanics of cell-cell separation. By variation of parameters, we are able to recover well-known limits of the Johnson-Kendall-Roberts theory, the Derjaguin-Muller-Toporov model, adhesive vesicles with surface tension (Brochard-Wyart and de Gennes derivation), and thin elastic shells. We further locate biological cells on this parameter space by comparison to existing experiments on S180 cells. Using this model, we show that mechanical parameters can be obtained that are consistent with both dual pipette aspiration and micropipette aspiration, a problem not successfully tackled so far. We estimate a cortex elastic modulus of E c ≈ 15 kPa, an effective cortex thickness of t c ≈ 0.3 μ m, and an active tension of γ ≈ 0.4 nN/ μ m. With these parameters, a Johnson-Kendall-Roberts-like scaling of the separation force is recovered. Finally, the change of contact radius with applied force in a pull-off experiment was investigated. For small forces, a scaling similar to both the Brochard-Wyart and de Gennes derivation and the Derjaguin-Muller-Toporov model is found.
Abstract:We explore two-and three-state Markov models driven out of thermal equilibrium by non-potential forces, to demonstrate basic properties of the steady heat capacity based on the concept of quasistatic excess heat. It is shown that large enough driving forces can make the steady heat capacity negative. For both the low-and high-temperature regimes we propose an approximative thermodynamic scheme in terms of "dynamically renormalized" effective energy levels. PACS
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