Cellular organelles move within the cellular volume and the effect of the resulting drag forces on the liquid causes bulk movement in the cytosol. The movement of both organelles and cytosol leads to an overall motion...Cellular organelles move within the cellular volume and the effect of the resulting drag forces on the liquid causes bulk movement in the cytosol. The movement of both organelles and cytosol leads to an overall motion pattern called cytoplasmic streaming or cyclosis. This streaming enables the active and passive transport of molecules and orga- nelles between cellular compartments. Furthermore, the fusion and budding of vesicles with and from the plasma mem- brane （exo/endocytosis） allow for transport of material between the inside and the outside of the cell. In the pollen tube, cytoplasmic streaming and exo/endocytosis are very active and fulfill several different functions. In this review, we focus on the logistics of intracellular motion and transport processes as well as their biophysical underpinnings. We discuss various modeling attempts that have been performed to understand both long-distance shuttling and short-distance targeting of organelles. We show how the combination of mechanical and mathematical modeling with cell biological approaches has contributed to our understanding of intracellular transport logistics.展开更多
Variable ventilation (VV) is a novel strategy of ventilatory support that utilizes random variations in the delivered tidal volume (VT) to improve lung function. Since the stretch pattern during VV has been shown to i...Variable ventilation (VV) is a novel strategy of ventilatory support that utilizes random variations in the delivered tidal volume (VT) to improve lung function. Since the stretch pattern during VV has been shown to increase surfactant release both in animals and cell culture, we hypothesized that there were combinations of PEEP and VT during VV that led to improved alveolar recruitment compared to conventional mechanical ventilation (CV). To test this hypothesis, we developed a computational model of stretch-induced surfactant release combined with abnormal alveolar mechanics of the injured lung under mechanical ventilation. We modeled the lung as a set of distinct acini with independent surfactant secretion and thus pressure-volume relationships. The rate of surfactant secretion was modulated by the stretch magnitude that an alveolus experienced per breath. Mechanical ventilation was simulated by delivering a prescribed VT at each breath. The fractional VT that each acinus received depended on its local compliance relative to the total system compliance. Regional variability in VT thus developed through feedback between stretch and surfactant release and coupling of regional VT to ventilator settings. The model allowed us to simulate patient-ventilator interactions over a wide range of PEEPs and VTs during CV and VV. Full recruitment was achieved through VV at a lower PEEP than required for CV. During VV, the acini were maintained under non-equilibrium steady-state conditions with breath-by-breath fluctuations of regional VT. In CV, alveolar injury was prevented with high-PEEP-low-VT or low-PEEP-high-VT combinations. In contrast, one contiguous region of PEEP-VT combinations allowed for full recruitment without overdistention during VV. We found that maintaining epithelial cell stretch above a critical threshold with either PEEP or VT may help stabilize the injured lung. These results demonstrate the significance of patient-ventilator coupling through the influence of cellular stretch-induced surfactant release展开更多
Insulin secreted by pancreatic islet ˇ-cells is the principal regulating hormone of glucose metabolism.Disruption of insulin secretion may cause glucose to accumulate in the blood, and result in diabetes mellitus.Alt...Insulin secreted by pancreatic islet ˇ-cells is the principal regulating hormone of glucose metabolism.Disruption of insulin secretion may cause glucose to accumulate in the blood, and result in diabetes mellitus.Although deterministic models of the insulin secretion pathway have been developed, the stochastic aspect of this biological pathway has not been explored. The first step in this direction presented here is a hybrid model of the insulin secretion pathway, in which the delayed rectifying KCchannels are treated as stochastic events. This hybrid model can not only reproduce the oscillation dynamics as the deterministic model does, but can also capture stochastic dynamics that the deterministic model does not. To measure the insulin oscillation system behavior, a probability-based measure is proposed and applied to test the effectiveness of a new remedy.展开更多
文摘Cellular organelles move within the cellular volume and the effect of the resulting drag forces on the liquid causes bulk movement in the cytosol. The movement of both organelles and cytosol leads to an overall motion pattern called cytoplasmic streaming or cyclosis. This streaming enables the active and passive transport of molecules and orga- nelles between cellular compartments. Furthermore, the fusion and budding of vesicles with and from the plasma mem- brane （exo/endocytosis） allow for transport of material between the inside and the outside of the cell. In the pollen tube, cytoplasmic streaming and exo/endocytosis are very active and fulfill several different functions. In this review, we focus on the logistics of intracellular motion and transport processes as well as their biophysical underpinnings. We discuss various modeling attempts that have been performed to understand both long-distance shuttling and short-distance targeting of organelles. We show how the combination of mechanical and mathematical modeling with cell biological approaches has contributed to our understanding of intracellular transport logistics.
文摘Variable ventilation (VV) is a novel strategy of ventilatory support that utilizes random variations in the delivered tidal volume (VT) to improve lung function. Since the stretch pattern during VV has been shown to increase surfactant release both in animals and cell culture, we hypothesized that there were combinations of PEEP and VT during VV that led to improved alveolar recruitment compared to conventional mechanical ventilation (CV). To test this hypothesis, we developed a computational model of stretch-induced surfactant release combined with abnormal alveolar mechanics of the injured lung under mechanical ventilation. We modeled the lung as a set of distinct acini with independent surfactant secretion and thus pressure-volume relationships. The rate of surfactant secretion was modulated by the stretch magnitude that an alveolus experienced per breath. Mechanical ventilation was simulated by delivering a prescribed VT at each breath. The fractional VT that each acinus received depended on its local compliance relative to the total system compliance. Regional variability in VT thus developed through feedback between stretch and surfactant release and coupling of regional VT to ventilator settings. The model allowed us to simulate patient-ventilator interactions over a wide range of PEEPs and VTs during CV and VV. Full recruitment was achieved through VV at a lower PEEP than required for CV. During VV, the acini were maintained under non-equilibrium steady-state conditions with breath-by-breath fluctuations of regional VT. In CV, alveolar injury was prevented with high-PEEP-low-VT or low-PEEP-high-VT combinations. In contrast, one contiguous region of PEEP-VT combinations allowed for full recruitment without overdistention during VV. We found that maintaining epithelial cell stretch above a critical threshold with either PEEP or VT may help stabilize the injured lung. These results demonstrate the significance of patient-ventilator coupling through the influence of cellular stretch-induced surfactant release
基金supported by the National Science Foundation under award DMS-1225160,CCF-0726763,and CCF-0953590the National Institutes of Health under award GM078989
文摘Insulin secreted by pancreatic islet ˇ-cells is the principal regulating hormone of glucose metabolism.Disruption of insulin secretion may cause glucose to accumulate in the blood, and result in diabetes mellitus.Although deterministic models of the insulin secretion pathway have been developed, the stochastic aspect of this biological pathway has not been explored. The first step in this direction presented here is a hybrid model of the insulin secretion pathway, in which the delayed rectifying KCchannels are treated as stochastic events. This hybrid model can not only reproduce the oscillation dynamics as the deterministic model does, but can also capture stochastic dynamics that the deterministic model does not. To measure the insulin oscillation system behavior, a probability-based measure is proposed and applied to test the effectiveness of a new remedy.
