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  • Occluding junctions as novel regulators of tissue mechanics during wound repair
    Publication . Carvalho, Lara; Patricio, Pedro; Ponte, Susana; Heisenberg, Carl-Philipp; Almeida, Luís; Nunes, André S.; Araujo, Nuno; Jacinto, Antonio
    In epithelial tissues, cells tightly connect to each other through cell-cell junctions, but they also present the remarkable capacity of reorganizing themselves without compromising tissue integrity. Upon injury, simple epithelia efficiently resolve small lesions through the action of actin cytoskeleton contractile structures at the wound edge and cellular rearrangements. However, the underlying mechanisms and how they cooperate are still poorly understood. In this study, we combine live imaging and theoretical modeling to reveal a novel and indispensable role for occluding junctions (OJs) in this process. We demonstrate that OJ loss of function leads to defects in wound-closure dynamics: instead of contracting, wounds dramatically increase their area. OJ mutants exhibit phenotypes in cell shape, cellular rearrangements, and mechanical properties as well as in actin cytoskeleton dynamics at the wound edge. We propose that OJs are essential for wound closure by impacting on epithelial mechanics at the tissue level, which in turn is crucial for correct regulation of the cellular events occurring at the wound edge.
  • Inheritances, social classes, and wealth distribution
    Publication . Patricio, Pedro; Araujo, Nuno
    We consider a simple theoretical model to investigate the impact of inheritances on the wealth distribution. Wealth is described as a finite resource, which remains constant over different generations and is divided equally among offspring. All other sources of wealth are neglected. We consider different societies characterized by a different offspring probability distribution. We find that, if the population remains constant, the society reaches a stationary wealth distribution. We show that inequality emerges every time the number of children per family is not always the same. For realistic offspring distributions from developed countries, the model predicts a Gini coefficient of G approximate to 0.3. If we divide the society into wealth classes and set the probability of getting married to depend on the distance between classes, the stationary wealth distribution crosses over from an exponential to a power-law regime as the number of wealth classes and the level of class distinction increase.
  • Convection patterns gradients of non-living and living micro-entities in hydrogels
    Publication . Canadas, Raphaël F.; Patricio, Pedro; Brancato, Virginia; Gasperini, Luca; Caballero, David; Pires, Ricardo A.; Costa, João; Pereira, Hélder; Yong, Ping; da Silva, Lucília P.; Chen, Jie; Kundu, Subhas C.; Araujo, Nuno; Reis, Rui L.; Marques, AP; Oliveira, Joaquim M.
    Inducing thermal gradients in two injected fluid systems results in the temporal formation of mixing conductive streams. If preserved through sol-gel transition, this mechanism can be used to drive and pattern non-living and living entities in mixed hydrogels. Interfaces are vital in nature, where gradients of non-living and living entities build distinct yet continuous integrated living tissues. However, the common tissue fabrication methodologies often result in dissimilar interfaces, lacking continuity through the interfaced engineered tissues. Thus, there is an urgent need for the fabrication of heterotypic but continuous engineered tissues with spatial control over biomimetic features. Here, we demonstrate the influence of gel injection temperature on the patterning of gradients of non-living and living entities. The experimental part was confirmed by numerical modelling, showing the formation of convective lines which spatially drive microscale microparticle and cells when different temperatures are applied in the sequential injection of two gels. Based on this finding, pure gellan gum (GG) and blended GG with methacrylated gelatin (Ge1MA) systems were used to program the formation of gradient features in hydrogels, such as microparticle and cells distribution patterns, polymeric bioactivity, degradation, controlled release, and stiffness. The correlation between gel injection temperature and gradients formation can be applied to tissue interface modelling, regeneration, drug release systems, and broader materials engineering fields.
  • Smoluchowski equations for linker-mediated irreversible aggregation
    Publication . Tavares, Jose; Antunes, Goncalo C.; Dias, Cristóvão; da Gama, M. M. Telo; Araujo, Nuno
    We developed a generalized Smoluchowski framework to study linker-mediated aggregation, where linkers and particles are explicitly taken into account. We assume that the bonds between linkers and particles are irreversible, and that clustering occurs through limited diffusion aggregation. The kernel is chosen by analogy with single-component diffusive aggregation but the clusters are distinguished by their number of particles and linkers. We found that the dynamics depends on three relevant factors, all tunable experimentally: (i) the ratio of the diffusion coefficients of particles and linkers; (ii) the relative number of particles and linkers; and (iii) the maximum number of linkers that may bond to a single particle. To solve the Smoluchoski equations analytically we employ a scaling hypothesis that renders the fraction of bondable sites of a cluster independent of the size of the cluster, at each instant. We perform numerical simulations of the corresponding lattice model to test this hypothesis. We obtain results for the asymptotic limit, and the time evolution of the bonding probabilities and the size distribution of the clusters. These findings are in agreement with experimental results reported in the literature and shed light on unexplained experimental observations.
  • Dynamics of a network fluid within the liquid–gas coexistence region
    Publication . Dias, Cristóvão; Tavares, Jose; Araujo, Nuno; Gama, Margarida
    Low-density networks of molecules or colloids are formed at low temperatures when the interparticle interactions are valence limited. Prototypical examples are networks of patchy particles, where the limited valence results from highly directional pairwise interactions. We combine extensive Langevin simulations and Wertheim's theory of association to study these networks. We find a scale-free (relaxation) dynamics within the liquid–gas coexistence region, which differs from that usually observed for isotropic particles. While for isotropic particles the relaxation dynamics is driven by surface tension (coarsening), when the valence is limited, the slow relaxation proceeds through the formation of an intermediate non-equilibrium gel via a geometrical percolation transition in the Random Percolation universality class. We show that the slow dynamics is universal, being also observed outside the coexistence region at low temperatures in the single phase region.
  • Dynamics of patchy particles in and out of equilibrium
    Publication . Tavares, Jose; Dias, Cristóvão; Araujo, Nuno; Gama, Margarida
    We combine particle-based simulations, mean-field rate equations, and Wertheim's theory to study the dynamics of patchy particles in and out of equilibrium, at different temperatures and densities. We consider an initial random distribution of nonoverlapping three-patch particles, with no bonds, and analyze the time evolution of the breaking and bonding rates of a single bond. We find that the asymptotic (equilibrium) dynamics differs from the initial (out of equilibrium) one. These differences are expected to depend on the initial conditions, temperature, and density.