Project description:Coordinated motions of close-packed multicellular systems typically generate cooperative packs, swirls, and clusters. These cooperative motions are driven by active cellular forces, but the physical nature of these forces and how they generate collective cellular motion remain poorly understood. Here, we study forces and motions in a confined epithelial monolayer and make two experimental observations: 1) the direction of local cellular motion deviates systematically from the direction of the local traction exerted by each cell upon its substrate; and 2) oscillating waves of cellular motion arise spontaneously. Based on these observations, we propose a theory that connects forces and motions using two internal state variables, one of which generates an effective cellular polarization, and the other, through contractile forces, an effective cellular inertia. In agreement with theoretical predictions, drugs that inhibit contractility reduce both the cellular effective elastic modulus and the frequency of oscillations. Together, theory and experiment provide evidence suggesting that collective cellular motion is driven by at least two internal variables that serve to sustain waves and to polarize local cellular traction in a direction that deviates systematically from local cellular velocity.
Project description:Collective cell polarization and alignment play important roles in tissue morphogenesis, wound healing and cancer metastasis. How cells sense the direction and position in these processes, however, has not been fully understood. Here we construct a theoretical model based on describing cell layer as a nemato-elastic medium, by which the cell polarization, cell alignment and cell active contraction are explicitly expressed as functions of components of the nematic order parameter. To determine the order parameter we derive two sets of governing equations, one for the force equilibrium of the system, and the other for the minimization of the system's free energy including the energy of cell polarization and alignment. By solving these coupled governing equations, we can predict the effects of substrate stiffness, geometries of cell layers, external forces and myosin activity on the direction- and position-dependent cell aspect ratio and cell orientation. Moreover, the axisymmetric problem with cells on a ring-like pattern is solved analytically, and the analytical solution for cell aspect ratio are governed by parameter groups which include the stiffness of the cell and the substrate, the strength of myosin activity and the external forces. Our predictions of the cell aspect ratio and orientation are generally comparable to experimental observations. These results show that the pattern of cell polarization is determined by the anisotropic degree of active contractile stress, and suggest a stress-driven polarization mechanism that enables cells to sense their spatial positions to develop direction- and position-dependent behavior. This, in turn, sheds light on the ways to control pattern formation in tissue engineering for potential biomedical applications.
Project description:Over the last decade, several countries around the world developed a collective sense of doom and gloom: Their Zeitgeist could be characterized as one of decline. Paradoxically, in some countries, such as the Netherlands, this collective discontent with society seems to exist despite high levels of individual well-being. Current psychological research informs us about why individuals would feel unduly optimistic, but does not account for a collective sense of decline. The present research develops a novel operationalization of Zeitgeist, referred to as a general factor Z. We conceptualize Zeitgeist as a collective global-level evaluation of the state (and future) of society. Three studies confirm that perceptions of the same societal problems at the personal and collective level differed strongly. Across these studies we found support for a hypothesized latent factor Z, underlying collective-level perceptions of society. This Z-factor predicted people's interpretation of new information about society that was presented through news stories. These results provide a first step in operationalizing and (ultimately) understanding the concept of Zeitgeist: collectively shared ideas about society. Implications for policy are discussed.
Project description:Animal groups frequently move in a highly organized manner, as represented by flocks of birds and schools of fish. Despite being an everyday occurrence, we do not fully understand how this works. In particular, what social interactions between animals give rise to the flock structures we observe? This question is often investigated using self-propelled particle models where particles represent the individual animals. These models differ in the social interactions used, individual particle properties, and various technical assumptions. One particular technical assumption relates to whether all particles update their headings and positions at exactly the same time (synchronous update) or not (asynchronous update). Here, we investigate the causal effects of this assumption in an attraction-only model and find that it has a dramatic impact. Polarized groups do not form when synchronous update is used, but are produced with asynchronous update, and this phenomenon is robust with respect to variation in particle displacements and inclusion of noise. Given that many important models have been implemented with synchronous update only, we speculate that our understanding of the social interactions on which they are based may be incomplete. Perhaps previously unobserved phenomena will emerge if other potentially more realistic update schemes are used.
Project description:In recent years, nanomechanics has evolved into a mature field, and it has now reached a stage which enables the fabrication and study of ever more elaborate devices. This has led to the emergence of arrays of coupled nanomechanical resonators as a promising field of research serving as model systems to study collective dynamical phenomena such as synchronization or topological transport. From a general point of view, the arrays investigated so far can be effectively treated as scalar fields on a lattice. Moving to a scenario where the vector character of the fields becomes important would unlock a whole host of conceptually interesting additional phenomena, including the physics of polarization patterns in wave fields and their associated topology. Here we introduce a new platform, a two-dimensional array of coupled nanomechanical pillar resonators, whose orthogonal vibration directions encode a mechanical polarization degree of freedom. We demonstrate direct optical imaging of the collective dynamics, enabling us to analyze the emerging polarization patterns, follow their evolution with drive frequency, and identify topological polarization singularities.
Project description:Pattern-dependent collective behaviors of cells have recently raised intensive attention. However, the underlying mechanisms that regulate these behaviors are largely elusive. Here, we report a quantitative study, combining experiment and modeling, on cell polarization and arrangement on a micropatterned substrate. We show that cells exhibit position-dependent collective behaviors that can be regulated by geometry and stiffness of the patterned substrate. We find that the driving force for these collective behaviors is the in-plane maximum shear stress in the cell layer that directs the arrangement of cells. The larger the shear stress, the more the cells preferentially align and polarize along the direction of the maximum principal stress. We also find that the aspect ratio of cell polarization shape and the degree to which cells preferentially align along the direction of maximum principal stress exhibit a biphasic dependence on substrate rigidity, corresponding to our quantitative predictions that the magnitude of the maximum shear stress is biphasically dependent on the stiffness of the substrate. As such, the driving force of these cell collective behaviors can be quantified using the maximum shear stress.
Project description:Dachsous-Fat signaling via the Hippo pathway influences proliferation during Drosophila development, and some of its mammalian homologs are tumor suppressors, highlighting its role as a universal growth regulator. The Fat/Hippo pathway responds to morphogen gradients and influences the in-plane polarization of cells and orientation of divisions, linking growth with tissue patterning. Remarkably, the Fat pathway transduces a growth signal through the polarization of transmembrane complexes that responds to both morphogen level and gradient. Dissection of these complex phenotypes requires a quantitative model that provides a systematic characterization of the pathway. In the absence of detailed knowledge of molecular interactions, we take a phenomenological approach that considers a broad class of simple models, which are sufficiently constrained by observations to enable insight into possible mechanisms. We predict two modes of local/cooperative interactions among Fat-Dachsous complexes, which are necessary for the collective polarization of tissues and enhanced sensitivity to weak gradients. Collective polarization convolves level and gradient of input signals, reproducing known phenotypes while generating falsifiable predictions. Our construction of a simplified signal transduction map allows a generalization of the positional value model and emphasizes the important role intercellular interactions play in growth and patterning of tissues.
Project description:Social dilemmas are often shaped by actions involving uncertain returns only achievable in the future, such as climate action or voluntary vaccination. In this context, uncertainty may produce non-trivial effects. Here, we assess experimentally - through a collective risk dilemma - the effect of timing uncertainty, i.e. how uncertainty about when a target needs to be reached affects the participants' behaviors. We show that timing uncertainty prompts not only early generosity but also polarized outcomes, where participants' total contributions are distributed unevenly. Furthermore, analyzing participants' behavior under timing uncertainty reveals an increase in reciprocal strategies. A data-driven game-theoretical model captures the self-organizing dynamics underpinning these behavioral patterns. Timing uncertainty thus casts a shadow on the future that leads participants to respond early, whereas reciprocal strategies appear to be important for group success. Yet, the same uncertainty also leads to inequity and polarization, requiring the inclusion of new incentives handling these societal issues.
Project description:Excessive or prolonged recruitment of inflammatory monocytes to damaged tissue can significantly worsen patient outcomes. Monocytes migrate to sites of tissue inflammation in response to high local concentrations of CCL2, a chemokine that binds to and signals through the CCR2 receptor. While the role of CCR2 in cellular migration is well studied, it is unclear how CCR2 inhibition affects macrophage polarization and if multivalency can increase downstream signaling effects. Using affinity selection with a phage library, we identified a novel single-chain variable fragment (scFv) (58C) that binds specifically and with high affinity to the N-terminal domain of CCR2 ( KD = 59.8 nM). The newly identified 58C-scFv bound to native CCR2 expressed on macrophages and MDA-MB-231 cells, inhibited migration, and induced a pro-inflammatory M1-phenotype in macrophages. The M1/M2 macrophage phenotype ratio for monomeric 58C-scFv was significantly increased over the negative control by 1.0 × 104-fold (iNOS/Arg-1), 5.1 × 104-fold (iNOS/Mgl2), 3.4 × 105-fold (IL-6/Arg-1), and 1.7 × 106-fold (IL-6/Mgl2). The multivalent display of 58C-scFv on liposomes further reduced migration of both cell types by 25-40% and enhanced M1 polarization by 200% over monomeric 58C-scFv. These studies demonstrate that CCR2 inhibition polarizes macrophages toward an inflammatory M1 phenotype, and that multivalent engagement of CCR2 increases the effects of 58C-scFv on polarization and migration. These data provide important insights into the role of multivalency in modulating binding, downstream signaling, and cellular fate.
Project description:Political campaign slogans, such as 'Take back control of our country' (United Kingdom Independence Party) and 'The Netherlands ours again' (Dutch Party for Freedom), indicate that right-wing populism appeals to the belief that the country is 'ours', and therefore, 'we' have the exclusive right to determine what happens. We examined this sense of ownership of the country (i.e. collective psychological ownership [CPO]) with the related determination right in relation to exclusionary attitudes and voting behaviour. Among Dutch (Study 1, N = 572) and British (Study 2, N = 495) participants, we found that CPO explained anti-immigrant and anti-EU attitudes, and these attitudes in turn accounted for voting 'leave' in the 2016 Brexit referendum in the British sample (Study 2). Additionally, CPO was more strongly related to negative immigrant attitudes among right-wing Dutch participants, whereas it was more strongly related to negative EU attitudes and voting 'leave' among left-wing British participants. CPO contributes to the understanding of critical contemporary social attitudes and political behaviour.