Observed frequency-independent torque in flagellar bacterial motors optimizes space exploration

A surprising feature of many bacterial motors is the apparently conserved form of their torque-frequency relation. Experiments indicate that the torque provided by the bacterial rotary motor is approximately constant over a large range of angular speeds. This is observed in both monotrichous and peritrichous bacteria, independently of whether they are propelled by a proton flux or by a Na+ ion flux. If the relation between angular speed ω and swimming speed is linear, a ω-independent torque implies that the power spent in active motion is proportional to the instantaneous bacterial speed. Using realistic values of the relevant parameters, we show that a constant torque maximizes the volume of the region explored by a bacterium in a resource-depleted medium. Given that nutrients in the ocean are often concentrated in separate, ephemeral patches, we propose that the observed constancy of the torque may be a trait evolved to maximize bacterial survival in the ocean.Fil: Di Salvo, Mario Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; ArgentinaFil: Condat, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentin

Joint fitting reveals hidden interactions in tumor growth

Tumor growth is often the result of the simultaneous development of two or more cancer cell populations. Their interaction between them characterizes the system evolution. To obtain information about these interactions we apply the recently developed vector universality (VUN) formalism to various instances of competition between tumor populations. The formalism allows us: (a) to quantify the growth mechanisms of a HeLa cell colony, describing the phenotype switching responsible for its fast expansion, (b) to reliably reconstruct the evolution of the necrotic and viable fractions in both in vitro and in vivo tumors using data for the time dependences of the total masses, and (c) to show how the shedding of cells leading to subspheroid formation is beneficial to both the spheroid and subspheroid populations, suggesting that shedding is a strong positive influence on cancer dissemination

Translational thresholds in a core circadian clock model

Organisms have evolved in a daily cyclic environment, developing circadian cell-autonomous clocks that temporally organize a wide range of biological processes. Translation is a highly regulated process mainly associated with the activity of microRNAs (miRNAs) at the translation initiation step that impacts on the molecular circadian clock dynamics. Recently, a molecular titration mechanism was proposed to explain the interactions between some miRNAs and their target mRNAs; new evidence also indicates that regulation by miRNA is a nonlinear process such that there is a threshold level of target mRNA below which protein production is drastically repressed. These observations led us to use a theoretical model of the circadian molecular clock to study the effect of miRNA-mediated translational thresholds on the molecular clock dynamics. We model the translational threshold by introducing a phenomenological Hill equation for the kinetics of PER translation and show how the parameters associated with translation kinetics affect the period, amplitude, and time delays between clock mRNA and clock protein expression. We show that our results are useful for analyzing experiments related to the translational regulation of negative elements of transcriptional-translational feedback loops. We also provide new elements for thinking about the translational threshold as a mechanism that favors the emergence of circadian rhythmicity, the tuning of the period-delay relationship and the cell capacity to control the protein oscillation amplitude with almost negligible changes in the mRNA amplitudes.Fil: Nieto, Paula Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; ArgentinaFil: Condat, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentin

Modeling tumorspheres reveals cancer stem cell niche building and plasticity

Cancer stem cells have been shown to be critical to the development of a variety of solid cancers. The precise interplay mechanisms between cancer stem cells and the rest of a tissue are still not elucidated. To shed light on the interactions between stem and non-stem cancer cell populations we develop a two-population mathematical model, which is suitable to describe tumorsphere growth. Both interspecific and intraspecific interactions, mediated by the microenvironment, are included. We show that there is a tipping point, characterized by a transcritical bifurcation, where a purely non-stem cell attractor is replaced by a new attractor that contains both stem and differentiated cancer cells. The model is then applied to describe the outcome of a recent experiment. This description reveals that, while the intraspecific interactions are inhibitory, the interspecific interactions stimulate growth. This can be understood in terms of stem cells needing differentiated cells to reinforce their niches, and phenotypic plasticity favoring the de-differentiation of differentiated cells into cancer stem cells. We posit that this is a consequence of the deregulation of the quorum sensing that maintains homeostasis in healthy tissues.Fil: Benitez, Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; ArgentinaFil: Barberis, Lucas Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; ArgentinaFil: Condat, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentin

Impact of rainfall on Aedes aegypti populations

Aedes aegypti is the main vector of multiple diseases, such as dengue, Zika, and chikungunya. Due to modifications in weather patterns, its geographical range is continuously evolving. Temperature is a key factor for its expansion into regions with cool winters, but rainfall can also have a strong impact on the colonization of these regions, since larvae emerging after a rainfall are likely to die at temperatures below 10 °C. As climate change is expected to affect rainfall regimes, with a higher frequency of heavy storms and an increase in drought-affected areas, it is important to understand how different rainfall scenarios may shape Ae. aegypti's range. We develop a model for the population dynamics of Ae. aegypti, coupled with a rainfall model to study the effect of the temporal distribution of rainfall on mosquito abundance. Using a fracturing process, we then investigate the effect of a higher variability in the daily rainfall. As an example, we show that rainfall distribution is necessary to explain the geographic range of Ae. aegypti in Taiwan, an island characterized by rainy winters in the north and dry winters in the south. We also predict that a higher variability in the rainfall time distribution will decrease the maximum abundance of Ae. aegypti during the summer. An increase in daily rainfall variability will likewise enhance its extinction probability. Finally, we obtain a nonlinear relationship between dry season duration and extinction probability. These findings can have a significant impact on our ability to predict disease outbreaks.Fil: Valdez, Lucas Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina. Boston University; Estados UnidosFil: Sibona, Gustavo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; ArgentinaFil: Condat, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentin

A Growth Model for Multicellular Tumor Spheroids

Most organisms grow according to simple laws, which in principle can be derived from energy conservation and scaling arguments, critically dependent on the relation between the metabolic rate B of energy flow and the organism mass m. Although this relation is generally recognized to be of the form B(m) = mp, the specific value of the exponent p is the object of an ongoing debate, with many mechanisms being postulated to support different predictions. We propose that multicellular tumor spheroids provide an ideal experimental model system for testing these allometric growth theories, especially under controlled conditions of malnourishment and applied mechanical stress

Understanding the influence of substrate when growing tumorspheres

Background: Cancer stem cells are important for the development of many solid tumors. These cells receive promoting and inhibitory signals that depend on the nature of their environment (their niche) and determine cell dynamics. Mechanical stresses are crucial to the initiation and interpretation of these signals. Methods: A two-population mathematical model of tumorsphere growth is used to interpret the results of a series of experiments recently carried out in Tianjin, China, and extract information about the intraspecific and interspecific interactions between cancer stem cell and differentiated cancer cell populations. Results: The model allows us to reconstruct the time evolution of the cancer stem cell fraction, which was not directly measured. We find that, in the presence of stem cell growth factors, the interspecific cooperation between cancer stem cells and differentiated cancer cells induces a positive feedback loop that determines growth, independently of substrate hardness. In a frustrated attempt to reconstitute the stem cell niche, the number of cancer stem cells increases continuously with a reproduction rate that is enhanced by a hard substrate. For growth on soft agar, intraspecific interactions are always inhibitory, but on hard agar the interactions between stem cells are collaborative while those between differentiated cells are strongly inhibitory. Evidence also suggests that a hard substrate brings about a large fraction of asymmetric stem cell divisions. In the absence of stem cell growth factors, the barrier to differentiation is broken and overall growth is faster, even if the stem cell number is conserved. Conclusions: Our interpretation of the experimental results validates the centrality of the concept of stem cell niche when tumor growth is fueled by cancer stem cells. Niche memory is found to be responsible for the characteristic population dynamics observed in tumorspheres. The model also shows why substratum stiffness has a deep influence on the behavior of cancer stem cells, stiffer substrates leading to a larger proportion of asymmetric doublings. A specific condition for the growth of the cancer stem cell number is also obtainedFil: Benitez, Lucia. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; ArgentinaFil: Barberis, Lucas Miguel. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; ArgentinaFil: Vellón, Luciano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Condat, Carlos. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentin

Joint fitting reveals hidden interactions in tumor growth

Tumor growth is often the result of the simultaneous development of two or more cancer cell populations. Crucial to the system evolution are the interactions between these populations. To obtain information about these interactions we apply the recently developed vector universality (VUN) formalism to various instances of competition between tumor populations. The formalism allows us (a) to quantify the growth mechanisms of a HeLa cell colony, describing the phenotype switching responsible for its fast expansion, (b) to reliably reconstruct the evolution of the necrotic and viable fractions in both in vitro and in vivo tumors using data for the time dependences of the total masses alone, and (c) to show how the shedding of cells leading to sub-spheroid formation is beneficial to both the spheroid and sub-spheroid populations, suggesting that shedding is a strong positive influence on cancer dissemination.Instituto de Física de Líquidos y Sistemas Biológico

Lifetime of a target in the presence of N independent walkers

We study the survival probability of an immobile target in presence of N independent diffusing walkers. We address the problem of the Mean Target Lifetime and its dependence on the number and initial distribution of the walkers when the trapping is perfect or imperfect. We consider the diffusion on lattices and in the continuous space and we address the bulk limit corresponding to a density of diffusing particles and only one isolated trap. Also, we use intermittent motion for optimization of search strategies.Comment: 18 pages, 5 figures. Accepted for publication in Physica A