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To this end, we first quantified the dynamic heterogeneity by the peak height of four-point susceptibility. Remarkably, this quantity showed a linear relationship with cell density over many experimental samples. We then varied the heterogeneity, by changing cell density, and found this change altered the number of leader cells at the wound margin. At low heterogeneity, wound closure was slower, with decreased persistence, reduced coordination and disruptive leader-follower interactions. Finally, microscopic characterization of cell-substrate adhesions illustrated how heterogeneity influenced orientations of focal adhesions, affecting coordinated cell movements. Together, these results demonstrate the importance of dynamic heterogeneity in epithelial wound healing. This article is part of the theme issue 'Multi-scale analysis and modelling of collective migration in biological systems'.In animal groups, individual decisions are best characterized by probabilistic rules. Furthermore, animals of many species live in small groups. Probabilistic interactions among small numbers of individuals lead to a so-called intrinsic noise at the group level. Theory predicts that the strength of intrinsic noise is not a constant but often depends on the collective state of the group; hence, it is also called a state-dependent noise or a multiplicative noise. Surprisingly, such noise may produce collective order. However, only a few empirical studies on collective behaviour have paid attention to such effects owing to the lack of methods that enable us to connect data with theory. Here, we demonstrate a method to characterize the role of stochasticity directly from high-resolution time-series data of collective dynamics. We do this by employing two well-studied individual-based toy models of collective behaviour. We argue that the group-level noise may encode important information about the underlying processes at the individual scale. In summary, we describe a method that enables us to establish connections between empirical data of animal (or cellular) collectives and the phenomenon of noise-induced states, a field that is otherwise largely limited to the theoretical literature. This article is part of the theme issue 'Multi-scale analysis and modelling of collective migration in biological systems'.Glioblastoma multiforme (GBM) is the most aggressive form of brain cancer with a short median survival time. GBM is characterized by the hallmarks of aggressive proliferation and cellular infiltration of normal brain tissue. miR-451 and its downstream molecules are known to play a pivotal role in regulation of the balance of proliferation and aggressive invasion in response to metabolic stress in the tumour microenvironment (TME). Surgery-induced transition in reactive astrocyte populations can play a significant role in tumour dynamics. In this work, we develop a multi-scale mathematical model of miR-451-LKB1-AMPK-OCT1-mTOR pathway signalling and individual cell dynamics of the tumour and reactive astrocytes after surgery. We show how the effects of fluctuating glucose on tumour cells need to be reprogrammed by taking into account the recent history of glucose variations and an AMPK/miR-451 reciprocal feedback loop. The model shows how variations in glucose availability significantly affect the activity of signalling molecules and, in turn, lead to critical cell migration. The model also predicts that microsurgery of a primary tumour induces phenotypical changes in reactive astrocytes and stem cell-like astrocytes promoting tumour cell proliferation and migration by Cxcl5. Finally, we investigated a new anti-tumour strategy by Cxcl5-targeting drugs. This article is part of the theme issue 'Multi-scale analysis and modelling of collective migration in biological systems'.While only a single sperm may fertilize the egg, getting to the egg can be facilitated, and possibly enhanced, by sperm group dynamics. Examples range from the trains formed by wood mouse sperm to the bundles exhibited by echidna sperm. In addition, observations of wave-like patterns exhibited by ram semen are used to score prospective sample fertility for artificial insemination in agriculture. In this review, we discuss these experimental observations of collective dynamics, as well as describe recent mechanistic models that link the motion of individual sperm cells and their flagella to observed collective dynamics. Establishing this link in models involves negotiating the disparate time- and length scales involved, typically separated by a factor of 1000, to capture the dynamics at the greatest length scales affected by mechanisms at the shortest time scales. Finally, we provide some outlook on the subject, in particular, the open questions regarding how collective dynamics impacts fertility. PD0332991 This article is part of the theme issue 'Multi-scale analysis and modelling of collective migration in biological systems'.The morphogenesis of zebrafish posterior lateral line (PLL) is a good predictive model largely used in biology to study cell coordinated reorganization and collective migration regulating pathologies and human embryonic processes. PLL development involves the formation of a placode formed by epithelial cells with mesenchymal characteristics which migrates within the animal myoseptum while cyclically assembling and depositing rosette-like clusters (progenitors of neuromast structures). The overall process mainly relies on the activity of specific diffusive chemicals, which trigger collective directional migration and patterning. Cell proliferation and cascade of phenotypic transitions play a fundamental role as well. The investigation on the mechanisms regulating such a complex morphogenesis has become a research topic, in the last decades, also for the mathematical community. In this respect, we present a multiscale hybrid model integrating a discrete approach for the cellular level and a continuous description for the molecular scale. The resulting numerical simulations are then able to reproduce both the evolution of wild-type (i.e. normal) embryos and the pathological behaviour resulting form experimental manipulations involving laser ablation. A qualitative analysis of the dependence of these model outcomes from cell-cell mutual interactions, cell chemical sensitivity and internalization rates is included. The aim is first to validate the model, as well as the estimated parameter values, and then to predict what happens in situations not tested yet experimentally. This article is part of the theme issue 'Multi-scale analysis and modelling of collective migration in biological systems'.
My Website: https://www.selleckchem.com/products/PD-0332991.html
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