RESUMO
Flavins are a unique class of compounds that combine the features of singlet oxygen generators and redox-dependent fluorophores. From a broad family of flavin derivatives, deazaalloxazines are significantly underdeveloped from the point of view of photophysical properties. Herein, we report photophysics of 5-deazaalloxazine (1a) in water, acetonitrile, and some other solvents. In particular, triplet excited states of 1a in water and in acetonitrile were investigated using ultraviolet-visible (UV-Vis) transient absorption spectroscopy. The measured triplet lifetimes for 1a were all on the microsecond time scale (≈ 60 µs) in deoxygenated solutions. The quantum yield of S1 â T1 intersystem crossing for 1a in water was 0.43 based on T1 energy transfer from 1a to indicaxanthin (5) acting as acceptor and on comparative actinometric measurements using benzophenone (6). 1a was an efficient photosensitizer for singlet oxygen in aerated solutions, with quantum yields of singlet oxygen in methanol of about 0.76, compared to acetonitrile ~ 0.74, dichloromethane ~ 0.64 and 1,2-dichloroethane ~ 0.54. Significantly lower singlet oxygen quantum yields were obtained in water and deuterated water (Ð¤Δ ~ 0.42 and 0.44, respectively). Human red blood cells (RBC) were used as a cell model to study the antioxidant capacity in vitro and cytotoxic activity of 1a. Fluorescence-lifetime imaging microscopy (FLIM) data were analyzed by fluorescence lifetime parameters and distribution for different parts of the emission spectrum. Comparison of multidimensional fluorescent properties of RBC under physiological-like and oxidative-stress conditions in the presence and absence of 1a suggests its dual activity as probe and singlet-oxygen generator and opens up a pathway for using FLIM to analyze complex intracellular behavior of flavin-like compounds. These new data on structure-property relationship contribute to the body of information required for a rational design of flavin-based tools for future biological and biochemical applications.
Assuntos
Fármacos Fotossensibilizantes , Oxigênio Singlete , Humanos , Oxigênio Singlete/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Flavinas , Água/química , Compostos Orgânicos , OxirreduçãoRESUMO
In the current study, we tested a possible mechanism of low- and high-contrast image component discrimination by the vertebrate eye-brain system. Apparently the eye-brain system has to discriminate between the low-contrast image component formed by light scattered within the retina, due to interaction of photons with cells and their parts, and the high-contrast image component transmitted by excitons via the quantum mechanism. Presently, effects of pulsed electric fields applied to Müller cell (MC) intermediate filaments (IFs) on the efficiency of exciton propagation were explored. The effects of both pulse duration and amplitude were recorded. These experimental results show that the eye-brain system may be using signal modulation to discriminate between high- and low-contrast image components, improving our understanding of high-contrast vision in vertebrates.
Assuntos
Encéfalo/fisiologia , Eletricidade , Células Ependimogliais/fisiologia , Olho/fisiopatologia , Filamentos Intermediários/fisiologia , Luz , Animais , Encéfalo/efeitos da radiação , Células Ependimogliais/efeitos da radiação , Olho/efeitos da radiação , Filamentos Intermediários/efeitos da radiação , Teoria Quântica , SuínosRESUMO
We review the experimental evidence, from both historic and modern literature of thermodynamic properties, for the non-existence of a critical-point singularity on Gibbs density surface, for the existence of a critical density hiatus line between 2-phase coexistence, for a supercritical mesophase with the colloidal characteristics of a one-component 2-state phase, and for the percolation loci that bound the existence of gaseous and liquid states. An absence of any critical-point singularity is supported by an overwhelming body of experimental evidence dating back to the original pressure-volume-temperature (p-V-T) equation-of-state measurements of CO2 by Andrews in 1863, and extending to the present NIST-2019 Thermo-physical Properties data bank of more than 200 fluids. Historic heat capacity measurements in the 1960s that gave rise to the concept of "universality" are revisited. The only experimental evidence cited by the original protagonists of the van der Waals hypothesis, and universality theorists, is a misinterpretation of the isochoric heat capacity Cv. We conclude that the body of extensive scientific experimental evidence has never supported the Andrews-van der Waals theory of continuity of liquid and gas, or the existence of a singular critical point with universal scaling properties. All available thermodynamic experimental data, including modern computer experiments, are compatible with a critical divide at Tc, defined by the intersection of two percolation loci at gaseous and liquid phase bounds, and the existence of a colloid-like supercritical mesophase comprising both gaseous and liquid states.
RESUMO
Presently we report new unique optical and electric properties of Müller cell (MC) intermediate filaments (IFs). We inform that these IFs extracted from porcine retina are excellent conductors of light and electric current. Such IF properties may endow vertebrate eyes with high-contrast vision. The properties of the IFs allow a simple quantum-mechanical description that justifies the quantum mechanism (QM) for the light energy transfer between the inner and the outer limiting membranes. These properties also provide direct and unequivocal proof that QM works even in isolated IFs, while the classic theory admits no capacity for light transmission by objects that are so thin. Note that the length and diameter of the IFs were 117⯱â¯1.3 µm and 10.1⯱â¯0.07 nm, respectively. The QM avoids the light scattering effects, which could significantly reduce the visual contrast, by conducting light energy in the form of excitons (excited states). This scientific breakthrough may provide new insights for medical ophthalmology.
Assuntos
Impedância Elétrica , Células Ependimogliais/fisiologia , Filamentos Intermediários/fisiologia , Microscopia Eletrônica de Varredura , Animais , Células Ependimogliais/ultraestrutura , Filamentos Intermediários/ultraestrutura , Teoria Quântica , Sus scrofaRESUMO
BACKGROUND: The development of rapid methods for the determination of the soluble solids content (SSC) and total phenolic content (TPC) in fruit juices is of great interest. Soluble solids content is related to sensory attributes, whereas TPC is related to the antioxidant capacity of juices. The aim of this study was to develop and optimize the calibration models for the prediction of the SSC and TPC of strawberry juices from the spectra of fruit and juices. RESULTS: Near infrared (NIR) spectra were measured for strawberry fruit and ultraviolet (UV), visible (VIS), and NIR spectra were measured for juices. The partial least squares regression models were validated using the test sample set and their predictive ability was evaluated on the basis of determination coefficients (R2 P ) and root mean square error of prediction (RMSEP). For SSC the models with high predictive ability were obtained using spectra of fruit (R2 P = 0.929, RMSEP = 0.46%) or juices (R2 P = 0.979, RMSEP = 0.25%) in the NIR range. The optimal models for TPC were obtained using NIR spectra of fruit (R2 P = 0.834, RMSEP = 130.8 mg GA L-1 ) or UV-VIS-NIR spectra of juices (R2 P = 0.844, RMSEP = 126.7 mg GA L-1 ). CONCLUSION: The results show the potential of spectroscopy for predicting quality parameters of strawberry juices from the juice spectra itself or non-destructively from the fruit spectra. They may contribute to the development of fruit sorting systems to optimize their use in juice production, as well as fast-screening methods for quality control of juices. © 2019 Society of Chemical Industry.
Assuntos
Fragaria/química , Sucos de Frutas e Vegetais/análise , Espectrofotometria/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Calibragem , Frutas/química , Análise dos Mínimos Quadrados , Controle de QualidadeRESUMO
BACKGROUND: Determination of the total phenolic content (TPC) in olive oils is of great interest, as phenolic compounds affect the health benefits, sensory attributes and oxidative stability of olive oils. The aim of this study was to explore the feasibility of direct front-face fluorescence measurements coupled with chemometrics for developing multivatiate models for discrimination between virgin olive oils with low and high TPC and determination of TPC concentration. RESULTS: Parallel factor analysis and principal component analysis of fluorescence excitation-emission matrices (EEMs) of virgin olive oils revealed different fluorescent properties for samples with low and high TPC. A perfect discrimination of oils with low and high TPC was achieved using partial least squares (PLS) discriminant analysis. The best regression model for the prediction of TPC was based on the PLS analysis of the unfolded entire EEMs (R2 = 0.951, RPD = 4.0). CONCLUSIONS: The results show the potential of fluorescence spectroscopy for direct screening of virgin olive oils for TPC. This may contribute to the development of fast screening methods for TPC assessment, providing an alternative to conventional assays. The procedure is environmentally friendly and fulfils the requirements for green analytical chemistry. © 2018 Society of Chemical Industry.
Assuntos
Azeite de Oliva/química , Fenóis/química , Espectrometria de Fluorescência/métodos , Análise Discriminante , Análise dos Mínimos Quadrados , Oxirredução , Análise de Componente PrincipalRESUMO
Swelling of mitochondria plays an important role in the pathogenesis of human diseases by stimulating mitochondria-mediated cell death through apoptosis, necrosis, and autophagy. Changes in the permeability of the inner mitochondrial membrane (IMM) of ions and other substances induce an increase in the colloid osmotic pressure, leading to matrix swelling. Modeling of mitochondrial swelling is important for simulation and prediction of in vivo events in the cell during oxidative and energy stress. In the present study, we developed a computational model that describes the mechanism of mitochondrial swelling based on osmosis, the rigidity of the IMM, and dynamics of ionic/neutral species. The model describes a new biophysical approach to swelling dynamics, where osmotic pressure created in the matrix is compensated for by the rigidity of the IMM, i.e., osmotic pressure induces membrane deformation, which compensates for the osmotic pressure effect. Thus, the effect is linear and reversible at small membrane deformations, allowing the membrane to restore its normal form. On the other hand, the membrane rigidity drops to zero at large deformations, and the swelling becomes irreversible. As a result, an increased number of dysfunctional mitochondria can activate mitophagy and initiate cell death. Numerical modeling analysis produced results that reasonably describe the experimental data reported earlier.
Assuntos
Simulação por Computador , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismo , Modelos Biológicos , Pressão Osmótica , HumanosRESUMO
Specialized intermediate filaments (IFs) have critical importance for the clearness and uncommon transparency of vertebrate lens fiber cells, although the physical mechanisms involved are poorly understood. Recently, an unusual low-scattering light transport was also described in retinal Müller cells. Exploring the function of IFs in Müller cells, we have studied the morphology and distribution pattern of IFs and other cytoskeletal filaments inside the Müller cell main processes in the foveolar part of the avian (pied flycatcher) retina. We found that some IFs surrounded by globular nanoparticles (that we suggest are crystallines) are present in almost every part of the Müller cells that span the retina, including the microvilli. Unlike IFs implicated in the mechanical architecture of the cell, these IFs are not connected to any specific cellular membranes. Instead, they are organized into bundles, passing inside the cell from the endfeet to the photoreceptor, following the geometry of the processes, and repeatedly circumventing numerous obstacles. We believe that the presently reported data effectively confirm that the model of nanooptical channels built of the IFs may provide a viable explanation of Müller cell transparency.
Assuntos
Células Ependimogliais/ultraestrutura , Filamentos Intermediários/ultraestrutura , Retina/citologia , Aves Canoras/anatomia & histologia , Animais , Fenômenos Biofísicos , Células Ependimogliais/química , Células Ependimogliais/fisiologia , Retina/fisiologia , Aves Canoras/fisiologiaRESUMO
We report that the duration of the egg-to-imago development period of the Drosophila melanogaster, and the imago longevity, are both controllable by combinations of external 3-dimensional (3D) low-frequency electric and magnetic fields (LFEMFs). Both these periods may be reduced or increased by applying an appropriate configuration of external 3D LFEMFs. We report that the longevity of D. melanogaster imagoes correlates with the duration of the egg-to-imago development period of the respective eggs. We infer that metabolic processes in both eggs and imago are either accelerated (resulting in reduced time periods) or slowed down (resulting in increased time periods). We propose that external 3D LFEMFs induce electric currents in live systems as well as mechanical vibrations on sub-cell, whole-cell and cell-group levels. These external fields induce media polarization due to ionic motion and orientation of electric dipoles that could moderate the observed effects. We found that the longevity of D. melanogaster imagoes is affected by action of 3D LFEMFs on the respective eggs in the embryonic development period (EDP). We interpret this effect as resulting from changes in the regulation mechanism of metabolic processes in D. melanogaster eggs, inherited by the resulting imagoes. We also tested separate effects of either 3D electric or 3D magnetic fields, which were significantly weaker.
Assuntos
Drosophila melanogaster/embriologia , Drosophila melanogaster/efeitos da radiação , Campos Eletromagnéticos , Metamorfose Biológica/efeitos da radiação , Óvulo/crescimento & desenvolvimento , Óvulo/efeitos da radiação , Animais , Drosophila melanogaster/fisiologia , Longevidade/efeitos da radiação , Masculino , Fatores de TempoRESUMO
We studied action of one-dimensional, two-dimensional and three-dimensional low-frequency oscillating electric and magnetic fields on sugar metabolism in Saccharomyces cerevisiae cell culture. S. cerevisiae cells were grown on a minimal medium containing glucose (10%) as a carbon source and salts (0.3-0.5%) that supplied nitrogen, phosphorus and trace metals. We found that appropriate three-dimensional field patterns can either accelerate or inhibit sugar metabolism in yeast cells, as compared to control experiments. We also studied aerobic sugar metabolism, with similar results. Sugar metabolism was monitored by formation of pyruvate, acetate and CO2. We found that for the P1 parameter set the cell metabolism accelerates as evaluated by all of the monitored chemical products, and the cell density growth rate also accelerates, with opposite effects observed for the P2 parameter set. These parameter sets are introduced using D, ω, φ, B, ω', and φ' - vectors defining amplitudes, frequencies and phases of periodic electric and magnetic fields, respectively. Thus, the P1 parameter set: D = (2.6, 3.1, 2.2) V/cm; ω = (0.8, 1.6, 0.2) kHz; φ = (1.31, 0.9, 1.0) rad; B = (3.1, 7.2, 7.2) × 10(-4) T; ω' = (2.1, 1.3, 3.1) kHz; φ' = (0.4, 2.1, 2.8) rad; and the P2 parameter set: D = (4.3, 1.6, 3.8) V/cm; ω = (3.3, 1.8, 2.8) kHz; φ = (0.86, 1.1, 0.4) rad; B = (5.4, 1.3, 1.3) × 10(-4) T; ω' = (1.3, 1.7, 0.9) kHz; φ' = (2.6, 1.7, 1.7) rad. The effects obtained for the less complex field combinations that used one-dimensional or two-dimensional configurations, or omitted either the electric or the magnetic contribution, were significantly weaker than those obtained for the complete P1 and P2 parameter sets.
Assuntos
Acetatos/metabolismo , Dióxido de Carbono/metabolismo , Eletricidade , Campos Magnéticos , Piruvatos/metabolismo , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/metabolismo , CinéticaRESUMO
We studied photodecomposition dynamics of (SO2â¯XH) Van der Waals' (VdW) complexes and clusters in gas phase, with X = C2H, C2H3, and C2H5. SO2 was excited by frequency-doubled radiation of a tunable dye laser and resonance-enhanced multiphoton ionization was used to detect the C2H (m/z 25), C2H3 (m/z 27), and C2H5 (m/z 29) ions by time-of-flight mass spectroscopy. Spectra obtained at higher nozzle pressures (P0 > 2.5 atm) indicate formation of clusters. Detailed studies of the VdW complex structure were carried out by analyzing the rotational structure of the respective action spectra. We also performed ab initio theoretical analysis of structures of the VdW complexes and transitional states leading to photodecomposition. We find that the structure of the transition state is significantly different as compared to the equilibrium ground-state structure of the respective complex. The photodecomposition mechanism depends on the hydrocarbon molecule bound to SO2.
RESUMO
We demonstrate that the lifespan of Drosophila melanogaster population is controllable by a combination of external three-dimensional oscillating low-frequency electric and magnetic fields (3D OLFEMFs). The lifespan was decreased or increased in dependence of the parameters of the external 3D OLFEMFs. We propose that metabolic processes in D. melanogaster's body are either accelerated (in the case of reduced lifespan) or slowed down (in the case of increased lifespan) in function of 3D OLFEMFs that induce vibrational motions on sub-cellular and larger scales.
Assuntos
Drosophila melanogaster/fisiologia , Drosophila melanogaster/efeitos da radiação , Campos Eletromagnéticos , Longevidade/efeitos da radiação , Animais , Feminino , Masculino , Modelos Biológicos , Fatores de TempoRESUMO
Exchange resonance spectra of three sandwich devices containing nanolayers of Cr, Mn, Co, Ni, and Eu were recorded at 77 K. We found that these spectra are significantly different from those obtained earlier for Fe-SiO2-Au three-layer nanosandwich device. Detailed theoretical approach was developed to analyze the recorded spectra, g-factor values, and relaxation properties of the spin-polarized states in the nanolayers. We found that the g-factor values and spin-lattice relaxation rates may be adequately described by the spin-orbit scattering mechanism. Electric charge density fluctuations may also contribute to spin-lattice relaxation in nanolayers. Second-order effects in the relaxation mechanism were also briefly considered.
RESUMO
Presently exciton activation of enzymatic oxidation of ethanol by human alcohol dehydrogenase (ADH) 1A enzyme is reported. The ADH1A enzyme was activated by infrared (IR) excitons transferred over Müller cell (MC) intermediate filaments (IFs). These IR excitons were generated by energy liberated upon enzymatic ATP hydrolysis and transferred to IFs. Also, the emission spectrum was recorded of the electronically excited ADH1A NAD+ EtOH complexes obtained by energy transfer from IR excitons that traveled along IFs. These results support the hypothesis that ATP hydrolysis energy may be transmitted in vivo in the form of IR excitons, over the network of IFs, both within and between cells.
Assuntos
Células Ependimogliais , Filamentos Intermediários , Humanos , Células Ependimogliais/fisiologia , Hidrólise , Etanol , Trifosfato de AdenosinaRESUMO
The protonation/deprotonation equilibrium was investigated for N-p-chlorobenzyl-substituted (E)-4'-hydroxy stilbazolium halide, namely (E)-1-(4-chlorobenzyl)-4-(4-hydroxystyryl)pyridinium chloride (EPC). Absorption, emission and synchronous scanning spectra were used to explain the observed phenomena. The excited state lifetimes of the protonated and deprotonated forms of EPC were measured and discussed. Absorption spectra were used to determine its pK(a) value in the ground state. We conclude that the protonation/deprotonation equilibrium is not attained in the first excited state of EPC, for kinetic reasons. The quinoid and benzenoid structures of EPC in the ground and excited state are discussed in acidic and basic range of pH. Aqueous solutions of EPC were yellow at pH < 7 and red at pH > 7, and addition of alcohols (methanol or 2-propanol) enhanced this change. Therefore, quaternary stilbazolium salts were investigated for application as acid-base indicators.
RESUMO
Lumichrome photophysical properties at different pH were characterized by UV-vis spectroscopy and steady-state and time-resolved fluorescence techniques, in four forms of protonation/deprotonation: neutral form, two monoanions, and dianion. The excited-state lifetimes of these forms of lumichrome were measured and discussed. The results were compared to those obtained for similar forms of alloxazine and/or isoalloxazine, and also to those of 1-methyl- and 3-methyllumichrome and 1,3-dimethyllumichrome. The absorption, emission, and synchronous spectra of lumichrome, 1-methyl- and 3-methyllumichrome, and 1,3-dimethyllumichrome at different pH were measured and used in discussion of fluorescence of neutral and deprotonated forms of lumichrome. The analysis of steady-state and time-resolved spectra and the DFT calculations both predict that the N(1) monoanion and the N(1,3) dianion of lumichrome have predominantly isoalloxazinic structures. Additionally, we confirmed that neutral lumichrome exists in its alloxazinic form only, in both the ground and the excited state. We also confirmed the existence and the alloxazinic structure of a second N(3) monoanion. The estimated values of pK(a) = 8.2 are for the equilibrium between neutral lumichrome and alloxazinic and isoalloxazinic monoanions, with proton dissociation from N(1)-H and N(3)-H groups proceeding at the almost the same pH, while the second value pK(a) = 11.4 refers to the formation of the isoalloxazinic dianion in the ground state.
Assuntos
Equilíbrio Ácido-Base , Flavinas/química , Estrutura Molecular , Processos Fotoquímicos , Teoria QuânticaRESUMO
PURPOSE: To study luminescence, reflectance, and color stability of dental composites and ceramics. MATERIALS AND METHODS: IPS e.max, IPS Classic, Gradia, and Sinfony materials were tested, both unpolished (as-cast) and polished specimens. Coffee, tea, red wine, and distilled water (control) were used as staining drinks. Disk-shaped specimens were soaked in the staining drinks for up to 5 days. Color was measured by a colorimeter. Fluorescence was recorded using a spectrofluorometer, in the front-face geometry. Time-resolved fluorescence spectra were recorded using a laser nanosecond spectrofluorometer. RESULTS: The exposure of the examined dental materials to staining drinks caused changes in color of the composites and ceramics, with the polished specimens exhibiting significantly lower color changes as compared to unpolished specimens. Composites exhibited lower color stability as compared to ceramic materials. Water also caused perceptible color changes in most materials. The materials tested demonstrated significantly different initial luminescence intensities. Upon exposure to staining drinks, luminescence became weaker by up to 40%, dependent on the drink and the material. Time-resolved luminescence spectra exhibited some red shift of the emission band at longer times, with the lifetimes in the range of tens of nanoseconds. CONCLUSIONS: Unpolished specimens with a more developed surface have lower color stability. Specimens stored in water develop some changes in their visual appearance. The presently proposed methods are effective in evaluating the luminescence of dental materials. Luminescence needs to be tested in addition to color, as the two characteristics are uncorrelated. It is important to further improve the color and luminescence stability of dental materials.
Assuntos
Cor , Resinas Compostas , Porcelana Dentária , Luminescência , Café , Colorimetria , Polimento Dentário , Teste de Materiais , Espectrofotometria , Chá , Fatores de Tempo , VinhoRESUMO
Presently a detailed biophysical model describing reversible and irreversible swelling dynamics of Müller cells (MC) is reported. The model includes a biophysical block of ionic and neutral species transport via MC membrane, water transport induced by osmotic pressure and pressure generated by membrane deformations, MC membrane potential and membrane mechanical properties. The model describes reversible and irreversible MC swelling (MCS) using the same set of parameters. The model was used in fitting available experimental data, and produced numerical values of previously unknown model parameters, including those describing mechanical properties of Müller cell membrane (MCM) with respect to bending and stretching. Numerical experiments simulating MC swelling showed complex oscillation dynamics of the relevant parameters in physiological initial conditions. In particular, MC membrane potential (ΔΨMC) demonstrated complex oscillation dynamics, which may be described by a superposition of several oscillations with their periods in the milliseconds, 100-ms and seconds time ranges. Dynamics of reversible and irreversible MCS, and the transition criteria from reversible to irreversible MCS modes were determined in model simulations.
Assuntos
Células Ependimogliais , Neuroglia , Potenciais da Membrana , Neuroglia/metabolismo , Pressão Osmótica , Água/metabolismoRESUMO
Theoretical biophysical model is reported for mitochondrial swelling (MS) dynamics in vivo. This newly developed model is based on the detailed biophysical model of MS dynamics in vitro, where mechanical properties of the inner mitochondrial membrane (IMM) were taken into account. The present model of MS dynamics in vivo is capable of analyzing MS dynamic transition from the reversible (physiological) to the irreversible (pathological) mode. This model was used to describe myocytes, assuming 1000 mitochondria distributed homogeneously over the sarcoplasm. Solute transport through the myocyte membrane was described by simplified phenomenological mechanisms of solute uptake and release. Biophysical processes occurring in mitochondria within cells were similar to those included in the earlier reported in vitro biophysical model of MS dynamics. Additionally, in vivo MS dynamics was simulated in different initial conditions, with results different from those of the in vitro model. Note that the presently reported model is the first attempt to develop a detailed biophysical model for the analysis of MS dynamics in vivo, capable of reproducing the transition between reversible and irreversible MS dynamics.
Assuntos
Mitocôndrias , Membranas Mitocondriais , Fenômenos Biofísicos , Mitocôndrias/fisiologia , Membranas Mitocondriais/metabolismo , Dilatação Mitocondrial/fisiologiaRESUMO
Existing theoretical approaches were considered that allow modelling of mitochondrial swelling (MS) dynamics. Simple phenomenological kinetic models were reviewed. Simple and extended biophysical and bioenergetic models that ignore mechanical properties of inner mitochondrial membrane (IMM), and similar models that include these mechanical properties were also reviewed. Limitations of these models we considered, as regards correct modelling of MS dynamics. It was found that simple phenomenological kinetic models have significant limitations, due to dependence of the kinetic parameter values estimated by fitting of the experimental data on the experimental conditions. Additionally, such simple models provide no understanding of the detailed mechanisms behind the MS dynamics, nor of the dynamics of various system parameters during MS. Thus, biophysical and bioenergetic models ignoring IMM mechanical properties can't be used to model the transition between reversible and irreversible MS. However, simple and extended biophysical models that include IMM mechanical properties allow modelling the transition to irreversible swelling. These latter models are still limited due to significantly simplified description of biochemistry, compared to those of bioenergetic models. Finally, a strategy of model development is proposed, towards correct interpretation of the mitochondrial life cycle, including the effects of MS dynamics.