Thermodynamic analysis of the permeability of biological membranes to non-electrolytes

Integration of experimental studies with mathematical modeling allows insight into systems properties, prediction of perturbation effects and generation of hypotheses for further research. We present a comprehensive mathematical description of the cellular response of yeast to hyperosmotic shock. The model integrates a biochemical reaction network comprising receptor stimulation, mitogen-activated protein kinase cascade dynamics, activation of gene expression and adaptation of cellular metabolism with a thermodynamic description of volume regulation and osmotic pressure. Simulations agree well with experimental results obtained under different stress conditions or with specific mutants. The model is predictive since it suggests previously unrecognized features of the system with respect to osmolyte accumulation and feedback control, as confirmed with experiments. The mathematical description presented is a valuable tool for future studies on osmoregulation in yeast and-with appropriate modifications-other organisms. It also serves as a starting point for a comprehensive description of cellular signaling.Osmoregulation encompasses active processes with which cells monitor and adjust osmotic pressure and control shape, turgor and relative water content. Even individual cells in multicellular organisms respond to osmotic changes, and strategies of cellular adaptation are conserved from bacteria to human 1 . The yeast Saccharomyces cerevisiae is a suitable model system to study osmoregulation and a substantial amount of information is available on osmotic shockinduced signal transduction, control of gene expression and accumulation of osmolytes 2 .Osmoregulation is a homeostatic process, though commonly studied as a response to osmotic shock. Central to yeast osmotic adaptation is the high osmolarity glycerol (HOG) signaling system 2,3 (Fig. 1). S. cerevisiae monitors osmotic changes through the plasma membrane-localized sensor histidine kinase Sln1. Under ambient conditions, Sln1 is active and inhibits signaling. Upon loss of turgor pressure, Sln1 is inactivated 4 resulting in activation of a mitogen-activated protein (MAP) kinase cascade and phosphorylation of the MAP kinase Hog1. Active Hog1 accumulates in the nucleus where it affects gene expression. Two HOG target genes encode enzymes in glycerol production. Hence, activation of Hog1 stimulates the production of glycerol, which serves as an osmolyte to increase intracellular osmotic pressure. Glycerol accumulation is also controlled by rapid closing of the aquaglyceroporin Fps1, which is an osmolarity-regulated glycerol channel. Hog1 activation and Hog1-dependent transcriptional stimulation are transient processes, indicating rigorous feedback control. Several protein phosphatases are known as negative regulators of the pathway. Although the overall organization of the systems is well characterized, open questions concern the mechanisms underlying activation and deactivation of the system, feedback control and the causal relationship between different events in...

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“…According to the principles of irreversible thermodynamics 38,45 water flow can be related to the osmotic pressure difference as…”

Section: Biophysical Changes (Supplementarymentioning

confidence: 99%

Integrative model of the response of yeast to osmotic shock

et al. 2005

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“…Around the turn of the 19th century, STARLING and TUBBY [2] interpreted microvascular fluid and solute exchange as resulting from the balance between hydraulic and colloidosmotic pressures. This concept is still valid today, but the complete formulation of transmicrovascular exchange has become much more complex because water crosses biological membranes more easily than large solutes (namely, plasma proteins) do [3]. In fact, different equations describe water and solute fluxes [4].…”

Section: Number 1 In This Seriesmentioning

confidence: 99%

Physiology and pathophysiology of pleural fluid turnover

Miserocchi¹

1997

Eur Respir J

247

128

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Number 1 in this SeriesA review on pleural space is certainly most welcome, for the simple reason that on opening a textbook of physiology the concepts concerning pleural fluid turnover date back to 1927 [1]. The same comment, in fact, applies in general to microvascular water and solute exchange. This appears particularly misleading, considering the major advances achieved in the field over the last 70 yrs. Around the turn of the 19th century, STARLING and TUBBY [2] interpreted microvascular fluid and solute exchange as resulting from the balance between hydraulic and colloidosmotic pressures. This concept is still valid today, but the complete formulation of transmicrovascular exchange has become much more complex because water crosses biological membranes more easily than large solutes (namely, plasma proteins) do [3]. In fact, different equations describe water and solute fluxes [4].As a result, the general model of transcapillary fluid exchange still taught to students, based on fluid filtration at the arteriolar end of the capillary bed and reabsorption at the venular end, appears rather simplistic. Due to the different permeability to water and solutes, one could predict on a mathematical basis that such a model would lead to a progressive increase in interstitial protein concentration over time [3,4], a condition that cannot be confirmed experimentally.Similarly, the old hypothesis claiming that pleural fluid filters at parietal level and is reabsorbed through the visceral pleura [1] would imply that pleural liquid protein concentration would keep increasing with age, but again there are no indications that this occurs. The existence of partial restriction to the movement of large solutes, compared to that of water molecules, posed scientists the major problem of explaining how interstitial volume and protein concentration are kept fairly steady. Ideologically, this led to re-evaluation of lymphatics as the major route for interstitial fluid drainage. In fact, since lymphatics do not sieve proteins, they leave the interstitial protein concentration unaltered the latter depending only upon the sieving properties of the filtering membrane. Accordingly, the description of interstitial fluid homeostasis under steady state conditions is now being explained as a balance between capillary filtration and lymphatic absorption. Major validation of this model has come from the accumulating experimental data over the past 30 yrs concerning interstitial tissues [4] and serous spaces [5]. Interestingly, since the pioneering, work of STARLING and TUBBY [2] the pleural space has been used as a useful experimental model to study the interaction between microvascular filtration and lymphatic drainage.This article presents an integrated view of pleural fluid turnover, based on data gathered from experimental studies on animals over the last 15 yrs. The situation in man is, unfortunately, still poorly defined; yet, where possible, Under physiological conditions, the lung interstitium and the pleural space behave as function...

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“…The flux across the nucleocytoplasmic boundary is modeled as the product of a proportionality constant (the permeability P ) times the concentration difference across the nucleocytoplasmic boundary, as a direct consequence of the fact that the flux does not require additional energy input [56]. Thus, we fix the following Kedem-Katchalsky transmission conditions [29] (see also [45,10,55] for a mathematical and numerical treatment of this conditions) at the nuclear envelope:…”

Section: Facilitated Translocation Through the Nuclear Envelopementioning

confidence: 99%

A spatial model of cellular molecular trafficking including active transport along microtubules

Cangiani

Natalini

2010

Journal of Theoretical Biology

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To cite this version:A. Cangiani, R. Natalini. A spatial model of cellular molecular trafficking including active transport along microtubules. Journal of Theoretical Biology, Elsevier, 2010, 267 (4) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A SPATIAL MODEL OF CELLULAR MOLECULAR TRAFFICKING INCLUDING ACTIVE TRANSPORT ALONG MICROTUBULESA. CANGIANI * , R. NATALINI † Abstract. We consider models of Ran-driven nuclear transport of molecules such as proteins in living cells. The mathematical model presented is the first to take into account for the active transport of molecules along the cytoplasmic microtubules. All parameters entering the models are thoroughly discussed. The model is tested by numerical simulations based on Discontinuous Galerkin finite element methods. The numerical experiments are compared to the behavior observed experimentally.

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Thermodynamic analysis of the permeability of biological membranes to non-electrolytes

Cited by 2,019 publications

References 9 publications

Integrative model of the response of yeast to osmotic shock

Integrative model of the response of yeast to osmotic shock

Physiology and pathophysiology of pleural fluid turnover

A spatial model of cellular molecular trafficking including active transport along microtubules

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