Pub Date : 2015-12-01DOI: 10.1142/S1793048015500095
N. Galich
We analyze the experimental data on fluorescence of DNA complexes inside neutrophils in flow cytometry with nanometer spatial resolution. Fluorescence visualizes oxidative activity of DNA and unusual statistics for DNA complex of full set of chromosomes. The exponential increasing of high-order central moments for fluctuations of fluorescence intensity characterizes the existence of intermittency in oxidative activity of DNA. Intermittency depends on the scales (on rank) of DNA networks in given cells. In the large-scale networks (with the scales >12% size of the cells), here occurs the switching to the exponential decreasing of high-order central moments for fluctuations intensity, i.e. stable oxidative activity of DNA as it is assumed for small-scale gene networks. Distributions of Holder’s averages and high-order moments for fluctuations intensity depend on the health status and can be used for high sensitive diagnostics of health. Intermittency of large-scale correlations reflects general natural property of DNA activity and immune response on various perturbations. Intermittency reflects the mutual actions of all large-scale correlations in dense fractal networks for DNA activity and synchronization of all excitations and correlations of all chromosomes in the cells.
{"title":"Intermittency and Changing Stability of Oxidative Activity of DNA in Chromosomes Inside Living Cells for Medical Diagnostics","authors":"N. Galich","doi":"10.1142/S1793048015500095","DOIUrl":"https://doi.org/10.1142/S1793048015500095","url":null,"abstract":"We analyze the experimental data on fluorescence of DNA complexes inside neutrophils in flow cytometry with nanometer spatial resolution. Fluorescence visualizes oxidative activity of DNA and unusual statistics for DNA complex of full set of chromosomes. The exponential increasing of high-order central moments for fluctuations of fluorescence intensity characterizes the existence of intermittency in oxidative activity of DNA. Intermittency depends on the scales (on rank) of DNA networks in given cells. In the large-scale networks (with the scales >12% size of the cells), here occurs the switching to the exponential decreasing of high-order central moments for fluctuations intensity, i.e. stable oxidative activity of DNA as it is assumed for small-scale gene networks. Distributions of Holder’s averages and high-order moments for fluctuations intensity depend on the health status and can be used for high sensitive diagnostics of health. Intermittency of large-scale correlations reflects general natural property of DNA activity and immune response on various perturbations. Intermittency reflects the mutual actions of all large-scale correlations in dense fractal networks for DNA activity and synchronization of all excitations and correlations of all chromosomes in the cells.","PeriodicalId":88835,"journal":{"name":"Biophysical reviews and letters","volume":"10 1","pages":"187-199"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S1793048015500095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64047558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-12-01DOI: 10.1142/S1793048015500113
Yuri K. Shestopaloff
We consider a general growth mechanism, which acts at cellular level and above (organs, systems and whole organisms). Using its mathematical representation, the growth equation, we study the growth and division mechanisms of amoeba and fission yeast Schizosaccharomyces pombe. We show how this mechanism, together with biomolecular machinery, governs growth and reproduction of cells, and these organisms in particular. This mechanism provides revealing answers to fundamental questions of biology, like why cells grow and divide, why and when cells’ growth stops. It also sheds light on questions like why and how life originated and developed. Solving the growth equation, we obtain analytical expression for the growth curve of fission yeast as a function of geometrical characteristics and nutrient influxes for RNA and protein synthesis, and compare the computed growth curves with 85 experiments. Statistical evaluation shows that these growth curves correspond to experimental data significantly better than all p...
{"title":"Why Cells Grow and Divide? General Growth Mechanism and How it Defines Cells’ Growth, Reproduction and Metabolic Properties","authors":"Yuri K. Shestopaloff","doi":"10.1142/S1793048015500113","DOIUrl":"https://doi.org/10.1142/S1793048015500113","url":null,"abstract":"We consider a general growth mechanism, which acts at cellular level and above (organs, systems and whole organisms). Using its mathematical representation, the growth equation, we study the growth and division mechanisms of amoeba and fission yeast Schizosaccharomyces pombe. We show how this mechanism, together with biomolecular machinery, governs growth and reproduction of cells, and these organisms in particular. This mechanism provides revealing answers to fundamental questions of biology, like why cells grow and divide, why and when cells’ growth stops. It also sheds light on questions like why and how life originated and developed. Solving the growth equation, we obtain analytical expression for the growth curve of fission yeast as a function of geometrical characteristics and nutrient influxes for RNA and protein synthesis, and compare the computed growth curves with 85 experiments. Statistical evaluation shows that these growth curves correspond to experimental data significantly better than all p...","PeriodicalId":88835,"journal":{"name":"Biophysical reviews and letters","volume":"10 1","pages":"209-256"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S1793048015500113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64047612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-10-27DOI: 10.1142/S1793048015500071
J. M. Romero, C. Trenado
Progress towards detailed characterization of structural and biophysical properties of dendrites emphasizes the importance of finding analytical solutions for more realistic dendrite models with circular cross-section and varying diameter. In this regard, we employ symmetry methods and the passive cable theory to deduce a generalized analytical solution for electric propagation in a family of tapering dendrites. In particular, we study the effect of such tapering geometries on the obtained electric voltage. Simulations using the deduced analytical solution indicate that for a subfamily of tapering profiles neural integration is better than in the stereotypical profile given by a cylinder.
{"title":"Analytical Solution of a Tapering Cable Equation for Dendrites and Conformal Symmetry","authors":"J. M. Romero, C. Trenado","doi":"10.1142/S1793048015500071","DOIUrl":"https://doi.org/10.1142/S1793048015500071","url":null,"abstract":"Progress towards detailed characterization of structural and biophysical properties of dendrites emphasizes the importance of finding analytical solutions for more realistic dendrite models with circular cross-section and varying diameter. In this regard, we employ symmetry methods and the passive cable theory to deduce a generalized analytical solution for electric propagation in a family of tapering dendrites. In particular, we study the effect of such tapering geometries on the obtained electric voltage. Simulations using the deduced analytical solution indicate that for a subfamily of tapering profiles neural integration is better than in the stereotypical profile given by a cylinder.","PeriodicalId":88835,"journal":{"name":"Biophysical reviews and letters","volume":"10 1","pages":"175-185"},"PeriodicalIF":0.0,"publicationDate":"2015-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S1793048015500071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64047509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-10-27DOI: 10.1142/S1793048015500046
O. Flomenbom
Modeling the dynamics in nations from economical and sociological perspectives is a central theme in economics and sociology. Accurate models can predict and therefore help all the world's citizens. Yet, recent years have show that the current models are missing. Here, we develop a dynamical society-deciders model that can explain the stability in a nation, based on concepts from dynamics, ecology and socio-econo-physics; a nation has two groups that interconnect, the deciders and the society. We show that a nation is either stable or it collapses. This depends on just two coefficients that we relate with sociological and economical indicators. We define a new socio-economic indicator, fairness. Fairness can measure the stability in a nation and how probable a change favoring the society is. We compute fairness among all the world's nations. Interestingly, in comparison with other indicators, fairness shows that the USA loses its rank among Western democracies, India is the best among the 15 most populated nations, and Egypt, Libya and Tunisia have significantly improved their rankings as a result of recent revolutions, further increasing the probability of additional positive changes. Within the model, long lasting crises are solved rather than with increasing governmental spending or cuts with regulations that reduce the stability of the deciders, namely, increasing fairness, while, for example, shifting wealth in the direction of the people, and therefore increasing further opportunities.
{"title":"The Society-Deciders Model and Fairness in Nations","authors":"O. Flomenbom","doi":"10.1142/S1793048015500046","DOIUrl":"https://doi.org/10.1142/S1793048015500046","url":null,"abstract":"Modeling the dynamics in nations from economical and sociological perspectives is a central theme in economics and sociology. Accurate models can predict and therefore help all the world's citizens. Yet, recent years have show that the current models are missing. Here, we develop a dynamical society-deciders model that can explain the stability in a nation, based on concepts from dynamics, ecology and socio-econo-physics; a nation has two groups that interconnect, the deciders and the society. We show that a nation is either stable or it collapses. This depends on just two coefficients that we relate with sociological and economical indicators. We define a new socio-economic indicator, fairness. Fairness can measure the stability in a nation and how probable a change favoring the society is. We compute fairness among all the world's nations. Interestingly, in comparison with other indicators, fairness shows that the USA loses its rank among Western democracies, India is the best among the 15 most populated nations, and Egypt, Libya and Tunisia have significantly improved their rankings as a result of recent revolutions, further increasing the probability of additional positive changes. Within the model, long lasting crises are solved rather than with increasing governmental spending or cuts with regulations that reduce the stability of the deciders, namely, increasing fairness, while, for example, shifting wealth in the direction of the people, and therefore increasing further opportunities.","PeriodicalId":88835,"journal":{"name":"Biophysical reviews and letters","volume":"10 1","pages":"157-174"},"PeriodicalIF":0.0,"publicationDate":"2015-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S1793048015500046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64047488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-10-27DOI: 10.1142/S1793048015300029
V. Trusova
Amyloid fibrils represent a generic class of mechanically strong and stable biomaterials with extremely advantageous properties. Although amyloids were initially associated only with severe neurological disorders, the role of these structures nowadays is shifting from health debilitating to highly beneficial both in biomedical and technological aspects. Intensive involvement of fibrillar assemblies into the wide range of pathogenic and functional processes strongly necessitate the molecular level characterization of the structural, physical and elastic features of protein nanofibrils. In the present contribution, we made an attempt to highlight the up-to-date progress in the understanding of amyloid properties from the polymer physics standpoint. The fundamental insights into protein fibril behavior are essential not only for development of therapeutic strategies to combat the protein misfolding disorders but also for rational and precise design of novel biodegradable protein-based nanopolymers.
{"title":"Protein Fibrillar Nanopolymers: Molecular-Level Insights into Their Structural, Physical and Mechanical Properties","authors":"V. Trusova","doi":"10.1142/S1793048015300029","DOIUrl":"https://doi.org/10.1142/S1793048015300029","url":null,"abstract":"Amyloid fibrils represent a generic class of mechanically strong and stable biomaterials with extremely advantageous properties. Although amyloids were initially associated only with severe neurological disorders, the role of these structures nowadays is shifting from health debilitating to highly beneficial both in biomedical and technological aspects. Intensive involvement of fibrillar assemblies into the wide range of pathogenic and functional processes strongly necessitate the molecular level characterization of the structural, physical and elastic features of protein nanofibrils. In the present contribution, we made an attempt to highlight the up-to-date progress in the understanding of amyloid properties from the polymer physics standpoint. The fundamental insights into protein fibril behavior are essential not only for development of therapeutic strategies to combat the protein misfolding disorders but also for rational and precise design of novel biodegradable protein-based nanopolymers.","PeriodicalId":88835,"journal":{"name":"Biophysical reviews and letters","volume":"10 1","pages":"135-156"},"PeriodicalIF":0.0,"publicationDate":"2015-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S1793048015300029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64047436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-08-10DOI: 10.1142/s1793048022500047
Rakesh Sengupta, P. V. Raja Shekar
Spontaneous oscillations measured by local field potentials (LFPs), electroencephalograms and magnetoencephalograms exhibit a variety of oscillations spanning the frequency band of 1–100[Formula: see text]Hz in animals and humans. Both instantaneous power and phase of these ongoing oscillations have commonly been observed to correlate with pre-stimulus processing in animals and humans. However, despite numerous attempts it is not fully clear whether the same mechanisms can give rise to a range of oscillations as observed in vivo during resting-state spontaneous oscillatory activity of the brain. In this paper, we show how oscillatory activity can arise out of general recurrent on-center off-surround neural network. This work shows that (a) a complex-valued input to a class of biologically inspired recurrent neural networks can be shown to be mathematically equivalent to a combination of real-valued recurrent networks with real-valued feed-forward network, and (b) such a network can give rise to oscillatory signatures. We also validate the conjecture with results of simulation of complex-valued additive recurrent neural network.
{"title":"Oscillatory Dynamics in Complex Recurrent Neural Networks","authors":"Rakesh Sengupta, P. V. Raja Shekar","doi":"10.1142/s1793048022500047","DOIUrl":"https://doi.org/10.1142/s1793048022500047","url":null,"abstract":"Spontaneous oscillations measured by local field potentials (LFPs), electroencephalograms and magnetoencephalograms exhibit a variety of oscillations spanning the frequency band of 1–100[Formula: see text]Hz in animals and humans. Both instantaneous power and phase of these ongoing oscillations have commonly been observed to correlate with pre-stimulus processing in animals and humans. However, despite numerous attempts it is not fully clear whether the same mechanisms can give rise to a range of oscillations as observed in vivo during resting-state spontaneous oscillatory activity of the brain. In this paper, we show how oscillatory activity can arise out of general recurrent on-center off-surround neural network. This work shows that (a) a complex-valued input to a class of biologically inspired recurrent neural networks can be shown to be mathematically equivalent to a combination of real-valued recurrent networks with real-valued feed-forward network, and (b) such a network can give rise to oscillatory signatures. We also validate the conjecture with results of simulation of complex-valued additive recurrent neural network.","PeriodicalId":88835,"journal":{"name":"Biophysical reviews and letters","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64047309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-07-30DOI: 10.1142/S1793048015500034
Shanmugavel Chinnathambi, S. Karthikeyan, D. Velmurugan, N. Hanagata, P. Aruna, S. Ganesan
In the present study, the interaction of 5-Fluorouracil with herring sperm DNA is reported using spectroscopic and molecular modeling techniques. This binding study of 5-FU with hs-DNA is of paramount importance in understanding chemico–biological interactions for drug design, pharmacy and biochemistry without altering the original structure. The challenge of the study was to find the exact binding mode of the drug 5-Fluorouracil with hs-DNA. From the absorption studies, a hyperchromic effect was observed for the herring sperm DNA in the presence of 5-Fluorouracil and a binding constant of 6.153 × 103 M-1 for 5-Fluorouracil reveals the existence of weak interaction between the 5-Fluorouracil and herring sperm DNA. Ethidium bromide loaded herring sperm DNA showed a quenching in the fluorescence intensity after the addition of 5-Fluorouracil. The binding constants for 5-Fluorouracil stranded DNA and competitive bindings of 5-FU interacting with DNA–EB systems were examined by fluorescence spectra. The Stern–Volmer plots and fluorescence lifetime results confirm the static quenching nature of the drug-DNA complex. The binding constant Kb was 2.5 × 104 L mol-1 and the number of binding sites are 1.17. The 5-FU on DNA system was calculated using double logarithmic plot. From the Forster nonradiative energy transfer study it has been found that the distance of 5-FU from DNA was 4.24 nm. In addition to the spectroscopic results, the molecular modeling studies also revealed the major groove binding as well as the partial intercalation mode of binding between the 5-Fluorouracil and herring sperm DNA. The binding energy and major groove binding as -6.04 kcal mol-1 and -6.31 kcal mol-1 were calculated from the modeling studies. All the testimonies manifested that binding modes between 5-Fluorouracil and DNA were evidenced to be groove binding and in partial intercalative mode.
{"title":"Investigations on the Interactions of 5-Fluorouracil with Herring Sperm DNA: Steady State/Time Resolved and Molecular Modeling Studies","authors":"Shanmugavel Chinnathambi, S. Karthikeyan, D. Velmurugan, N. Hanagata, P. Aruna, S. Ganesan","doi":"10.1142/S1793048015500034","DOIUrl":"https://doi.org/10.1142/S1793048015500034","url":null,"abstract":"In the present study, the interaction of 5-Fluorouracil with herring sperm DNA is reported using spectroscopic and molecular modeling techniques. This binding study of 5-FU with hs-DNA is of paramount importance in understanding chemico–biological interactions for drug design, pharmacy and biochemistry without altering the original structure. The challenge of the study was to find the exact binding mode of the drug 5-Fluorouracil with hs-DNA. From the absorption studies, a hyperchromic effect was observed for the herring sperm DNA in the presence of 5-Fluorouracil and a binding constant of 6.153 × 103 M-1 for 5-Fluorouracil reveals the existence of weak interaction between the 5-Fluorouracil and herring sperm DNA. Ethidium bromide loaded herring sperm DNA showed a quenching in the fluorescence intensity after the addition of 5-Fluorouracil. The binding constants for 5-Fluorouracil stranded DNA and competitive bindings of 5-FU interacting with DNA–EB systems were examined by fluorescence spectra. The Stern–Volmer plots and fluorescence lifetime results confirm the static quenching nature of the drug-DNA complex. The binding constant Kb was 2.5 × 104 L mol-1 and the number of binding sites are 1.17. The 5-FU on DNA system was calculated using double logarithmic plot. From the Forster nonradiative energy transfer study it has been found that the distance of 5-FU from DNA was 4.24 nm. In addition to the spectroscopic results, the molecular modeling studies also revealed the major groove binding as well as the partial intercalation mode of binding between the 5-Fluorouracil and herring sperm DNA. The binding energy and major groove binding as -6.04 kcal mol-1 and -6.31 kcal mol-1 were calculated from the modeling studies. All the testimonies manifested that binding modes between 5-Fluorouracil and DNA were evidenced to be groove binding and in partial intercalative mode.","PeriodicalId":88835,"journal":{"name":"Biophysical reviews and letters","volume":"10 1","pages":"115-133"},"PeriodicalIF":0.0,"publicationDate":"2015-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S1793048015500034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64047452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-07-30DOI: 10.1142/S179304801550006X
A. Ryabov
In this paper, we review the tagged particle dynamics in a semi-infinite system with an absorbing boundary. The emphasis is on an interplay between the hard-core interparticle interaction and the absorption process. The exact probability density function for the position of a tagged particle is derived by means of probabilistic arguments. First, the initially homogeneous system with constant density of particles is studied. In this setting, the dynamics of the tracer conditioned on nonabsorption becomes subdiffusive, the generalized diffusion coefficient being different from that reported for the system without absorbing boundary. Second, the case when the initial number of particles is finite is discussed. In this case, in the long time limit the tracer diffusion is normal and the hard-core interaction manifests itself through the renormalization of the tracer diffusion coefficient. The Gaussian distribution derived for infinite single-file systems is, in the present semi-infinite setting, replaced by the Rayleigh distribution. Special Issue Comments: This article presents results on the dynamics of a tagged particle in open systems, where the number of particles is not conserved in time. This article is related to the Special Issue articles about advanced statistical properties in single file dynamics,1 the calculation of correlations,2 files with force3 and the zig-zag patterns in files.4
{"title":"Single-File System with Absorbing Boundary: Tracer Dynamics and First-Passage Properties","authors":"A. Ryabov","doi":"10.1142/S179304801550006X","DOIUrl":"https://doi.org/10.1142/S179304801550006X","url":null,"abstract":"In this paper, we review the tagged particle dynamics in a semi-infinite system with an absorbing boundary. The emphasis is on an interplay between the hard-core interparticle interaction and the absorption process. The exact probability density function for the position of a tagged particle is derived by means of probabilistic arguments. First, the initially homogeneous system with constant density of particles is studied. In this setting, the dynamics of the tracer conditioned on nonabsorption becomes subdiffusive, the generalized diffusion coefficient being different from that reported for the system without absorbing boundary. Second, the case when the initial number of particles is finite is discussed. In this case, in the long time limit the tracer diffusion is normal and the hard-core interaction manifests itself through the renormalization of the tracer diffusion coefficient. The Gaussian distribution derived for infinite single-file systems is, in the present semi-infinite setting, replaced by the Rayleigh distribution. Special Issue Comments: This article presents results on the dynamics of a tagged particle in open systems, where the number of particles is not conserved in time. This article is related to the Special Issue articles about advanced statistical properties in single file dynamics,1 the calculation of correlations,2 files with force3 and the zig-zag patterns in files.4","PeriodicalId":88835,"journal":{"name":"Biophysical reviews and letters","volume":"10 1","pages":"85-96"},"PeriodicalIF":0.0,"publicationDate":"2015-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S179304801550006X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64047503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-07-30DOI: 10.1142/S1793048015500058
M. Chaplain, Gibin G. Powathil
Cancer is a complex, multiscale process involving interactions at intracellular, intercellular and tissue scales that are in turn susceptible to microenvironmental changes. Each individual cancer cell within a cancer cell mass is unique, with its own internal cellular pathways and biochemical interactions. These interactions contribute to the functional changes at the cellular and tissue scale, creating a heterogenous cancer cell population. Anticancer drugs are effective in controlling cancer growth by inflicting damage to various target molecules and thereby triggering multiple cellular and intracellular pathways, leading to cell death or cell-cycle arrest. One of the major impediments in the chemotherapy treatment of cancer is drug resistance driven by multiple mechanisms, including multi-drug and cell-cycle mediated resistance to chemotherapy drugs. In this article, we discuss two hybrid multiscale modelling approaches, incorporating multiple interactions involved in the sub-cellular, cellular and microenvironmental levels to study the effects of cell-cycle, phase-specific chemotherapy on the growth and progression of cancer cells.
{"title":"Multiscale modelling of cancer progression and treatment control : the role of intracellular heterogeneities in chemotherapy treatment","authors":"M. Chaplain, Gibin G. Powathil","doi":"10.1142/S1793048015500058","DOIUrl":"https://doi.org/10.1142/S1793048015500058","url":null,"abstract":"Cancer is a complex, multiscale process involving interactions at intracellular, intercellular and tissue scales that are in turn susceptible to microenvironmental changes. Each individual cancer cell within a cancer cell mass is unique, with its own internal cellular pathways and biochemical interactions. These interactions contribute to the functional changes at the cellular and tissue scale, creating a heterogenous cancer cell population. Anticancer drugs are effective in controlling cancer growth by inflicting damage to various target molecules and thereby triggering multiple cellular and intracellular pathways, leading to cell death or cell-cycle arrest. One of the major impediments in the chemotherapy treatment of cancer is drug resistance driven by multiple mechanisms, including multi-drug and cell-cycle mediated resistance to chemotherapy drugs. In this article, we discuss two hybrid multiscale modelling approaches, incorporating multiple interactions involved in the sub-cellular, cellular and microenvironmental levels to study the effects of cell-cycle, phase-specific chemotherapy on the growth and progression of cancer cells.","PeriodicalId":88835,"journal":{"name":"Biophysical reviews and letters","volume":"10 1","pages":"97-114"},"PeriodicalIF":0.0,"publicationDate":"2015-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S1793048015500058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64047498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-07-30DOI: 10.1142/S1793048015500022
V. Zhdanov, V. Zhdanov
Enzymatic reactions occurring in vivo on lipid membranes can be influenced by various factors including macromolecular crowding in general and substrate aggregation in particular. In academic studies, the role of these factors can experimentally be clarified by tracking single-enzyme kinetics occurring on individual lipid vesicles. To extend the conceptual basis for such experiments, we analyze herein the corresponding kinetics mathematically with emphasis on the role of substrate aggregation. In general, the aggregation may occur on different length scales. Small aggregates may e.g. contain a few proteins or peptides while large aggregates may be mesoscopic as in the case of lipid domains which can be formed in the membranes composed of different lipids. We present a kinetic model describing comprehensively the effect of aggregation of the former type on the dependence of the reaction rate on substrate membrane concentration. The results obtained with physically reasonable parameters indicate that the aggregation-related deviations from the conventional Michaelis-Menten kinetics may be appreciable. Special Issue Comments: This theoretical article is focused on single-enzyme reactions occurring in parallel with substrate aggregation on individual vesicles. This subject is related to a few Special Issue articles concerning enzyme dynamics and function and mathematical aspects of stochastic kinetics.
{"title":"Kinetics of single-enzyme reactions on vesicles: Role of substrate aggregation","authors":"V. Zhdanov, V. Zhdanov","doi":"10.1142/S1793048015500022","DOIUrl":"https://doi.org/10.1142/S1793048015500022","url":null,"abstract":"Enzymatic reactions occurring in vivo on lipid membranes can be influenced by various factors including macromolecular crowding in general and substrate aggregation in particular. In academic studies, the role of these factors can experimentally be clarified by tracking single-enzyme kinetics occurring on individual lipid vesicles. To extend the conceptual basis for such experiments, we analyze herein the corresponding kinetics mathematically with emphasis on the role of substrate aggregation. In general, the aggregation may occur on different length scales. Small aggregates may e.g. contain a few proteins or peptides while large aggregates may be mesoscopic as in the case of lipid domains which can be formed in the membranes composed of different lipids. We present a kinetic model describing comprehensively the effect of aggregation of the former type on the dependence of the reaction rate on substrate membrane concentration. The results obtained with physically reasonable parameters indicate that the aggregation-related deviations from the conventional Michaelis-Menten kinetics may be appreciable. Special Issue Comments: This theoretical article is focused on single-enzyme reactions occurring in parallel with substrate aggregation on individual vesicles. This subject is related to a few Special Issue articles concerning enzyme dynamics and function and mathematical aspects of stochastic kinetics.","PeriodicalId":88835,"journal":{"name":"Biophysical reviews and letters","volume":"10 1","pages":"69-83"},"PeriodicalIF":0.0,"publicationDate":"2015-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S1793048015500022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64047445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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