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1.
Biophys J ; 118(7): 1721-1732, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32105650

RESUMO

Many multicellular communities propagate signals in a directed manner via excitable waves. Cell-to-cell heterogeneity is a ubiquitous feature of multicellular communities, but the effects of heterogeneity on wave propagation are still unclear. Here, we use a minimal FitzHugh-Nagumo-type model to investigate excitable wave propagation in a two-dimensional heterogeneous community. The model shows three dynamic regimes in which waves either propagate directionally, die out, or spiral indefinitely, and we characterize how these regimes depend on the heterogeneity parameters. We find that in some parameter regimes, spatial correlations in the heterogeneity enhance directional propagation and suppress spiraling. However, in other regimes, spatial correlations promote spiraling, a surprising feature that we explain by demonstrating that these spirals form by a second, distinct mechanism. Finally, we characterize the dynamics using techniques from percolation theory. Despite the fact that percolation theory does not completely describe the dynamics quantitatively because it neglects the details of the excitable propagation, we find that it accounts for the transitions between the dynamic regimes and the general dependency of the spiral period on the heterogeneity and thus provides important insights. Our results reveal that the spatial structure of cell-to-cell heterogeneity can have important consequences for signal propagation in cellular communities.

2.
PLoS Comput Biol ; 15(12): e1007508, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31790383

RESUMO

Signal propagation over long distances is a ubiquitous feature of multicellular communities, but cell-to-cell variability can cause propagation to be highly heterogeneous. Simple models of signal propagation in heterogenous media, such as percolation theory, can potentially provide a quantitative understanding of these processes, but it is unclear whether these simple models properly capture the complexities of multicellular systems. We recently discovered that in biofilms of the bacterium Bacillus subtilis, the propagation of an electrical signal is statistically consistent with percolation theory, and yet it is reasonable to suspect that key features of this system go beyond the simple assumptions of basic percolation theory. Indeed, we find here that the probability for a cell to signal is not independent from other cells as assumed in percolation theory, but instead is correlated with its nearby neighbors. We develop a mechanistic model, in which correlated signaling emerges from cell division, phenotypic inheritance, and cell displacement, that reproduces the experimentally observed correlations. We find that the correlations do not significantly affect the spatial statistics, which we rationalize using a renormalization argument. Moreover, the fraction of signaling cells is not constant in space, as assumed in percolation theory, but instead varies within and across biofilms. We find that this feature lowers the fraction of signaling cells at which one observes the characteristic power-law statistics of cluster sizes, consistent with our experimental results. We validate the model using a mutant biofilm whose signaling probability decays along the propagation direction. Our results reveal key statistical features of a correlated signaling process in a multicellular community. More broadly, our results identify extensions to percolation theory that do or do not alter its predictions and may be more appropriate for biological systems.


Assuntos
Microbiota/fisiologia , Modelos Biológicos , Bacillus subtilis/genética , Bacillus subtilis/fisiologia , Biofilmes , Biologia Computacional , Fenômenos Eletrofisiológicos , Dispositivos Lab-On-A-Chip , Interações Microbianas/fisiologia , Mutação , Potássio/metabolismo , Transdução de Sinais/fisiologia
3.
Cell Syst ; 7(2): 137-145.e3, 2018 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-30056004

RESUMO

Signal transmission among cells enables long-range coordination in biological systems. However, the scarcity of quantitative measurements hinders the development of theories that relate signal propagation to cellular heterogeneity and spatial organization. We address this problem in a bacterial community that employs electrochemical cell-to-cell communication. We developed a model based on percolation theory, which describes how signals propagate through a heterogeneous medium. Our model predicts that signal transmission becomes possible when the community is organized near a critical phase transition between a disconnected and a fully connected conduit of signaling cells. By measuring population-level signal transmission with single-cell resolution in wild-type and genetically modified communities, we confirm that the spatial distribution of signaling cells is organized at the predicted phase transition. Our findings suggest that at this critical point, the population-level benefit of signal transmission outweighs the single-cell level cost. The bacterial community thus appears to be organized according to a theoretically predicted spatial heterogeneity that promotes efficient signal transmission.


Assuntos
Bactérias/metabolismo , Interações Microbianas , Análise de Célula Única/métodos , Bactérias/citologia , Biofilmes , Eletroquímica , Microbiota , Modelos Biológicos , Transição de Fase
4.
J Phys Chem Lett ; 5(20): 3462-7, 2014 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-26278594

RESUMO

Singlet fission holds the potential to dramatically improve the efficiency of solar energy conversion by creating two triplet excitons from one photoexcited singlet exciton in organic semiconductors. It is generally assumed that the singlet-fission rate is linearly dependent on the exciton density. Here we experimentally show that the rate of singlet fission has a nonlinear dependence on the density of photoexcited singlet excitons in tetracene films with small crystalline grains. We disentangle the spectrotemporal features of singlet and triplet dynamics from ultrafast spectroscopic data with the algorithm of singular value decomposition. The correlation between their temporal dynamics indicates a superlinear dependence of fission rate on the density of singlet excitons, which may arise from excitonic interactions.

5.
Zhongguo Zhong Yao Za Zhi ; 33(1): 31-4, 2008 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-18338615

RESUMO

OBJECTIVE: To study the preparation of phenols gastric floating tablet. METHOD: The tablets which were prepared using Eudragit IV, HPMC(K4M), MCC101 and Octadecanol as excipients were evaluated by vitro floatation and releasing performance. The pressure of preparationg was also study to select the optimal preparation. RESULT: The tablets were successfully prepared in which the drug, Eudragit IV, Octadecanol were 31% respectively,and MCC101 was 7%. And 3-4 kg was found to be the eligible pressure. CONCLUSION: The study was found to be effective in the process of phenols gastric floating tablet.


Assuntos
Portadores de Fármacos , Fármacos Gastrointestinais/química , Fenóis/química , Comprimidos , Excipientes/química , Ácidos Polimetacrílicos/química , Tecnologia Farmacêutica/métodos
6.
Pharm Dev Technol ; 13(1): 37-47, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18300098

RESUMO

The in vitro performance of monolithic matrix systems containing the interpolyelectrolyte complex between chitosan and polycarbophil as excipient was evaluated in terms of their swelling, bioadhesive, and drug release properties. The different matrix systems showed excellent swelling properties without erosion, except for the formulation containing the highest quantity chitosan-polycarbophil complex that exhibited surface erosion in addition to swelling. All the different matrix systems exhibited significantly higher bioadhesive properties than the control group. Furthermore, they showed controlled insulin release without an initial burst release effect. However, only the matrix system that exhibited surface erosion in combination with swelling approached zero-order release.


Assuntos
Resinas Acrílicas/química , Quitosana/química , Sistemas de Liberação de Medicamentos , Excipientes/química , Adesivos , Varredura Diferencial de Calorimetria , Fenômenos Químicos , Físico-Química , Preparações de Ação Retardada , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Microscopia Eletrônica de Varredura , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Comprimidos
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