Vladimir Mat

Vladimir Matveev. The great basic question of science: Membrane compartment or non-membrane phase compartment is a physical basis for origin of life? Oral presentation at The 2nd All-Russian Conference on Astrobiology. Moscow, Pushchino, 5-9 June 2016. Video in English: Presentation slides in English as pdf: http://www.bioparadigma.spb.ru/conf/Matveev-2016-The.great.basic.question.of.science_Eng_Slides.pdf Comments for slides in English: http://www.bioparadigma.spb.ru/conf/Matveev-2016-The.great.basic.question.of.science_Comments_Eng.pdf

Main principles of Ling’s physical theory of the living cell: http://www.bioparadigma.spb.ru/files/Main.principles.of.Ling's.physical.theory.of.the.living.cell.pdf

Thanks!

Thanks. Do you have a controversial literature?

Dear Colleagues, I need a reference (for the article "Steady-state physiology…" I have just written) that proves the pumping role of Na,K-ATPase. I have tried to locate any publication that demonstrates the pumping function of Na,K-ATPase, but have found nothing. Please help me with references (even one would be enough). To make it clear what I need, let me to give the following clarification. We believe that the ionic asymmetry between the cell and its environment is provided by a plasma membrane pump, Na-K-ATPase. Because of this pump, the concentration of K+ in the cell is above that in the medium and the concentration of Na+ is lower than in the medium. The pump works continuously, using energy. Once the pump stops working, K+ leaves the cells, and Na+, conversely, enters them. If we turn on the pump again, it will start to pump Na+ out of the cells, and K+ will be pumped into the cell. The question is, what experiments should be designed to show that the membrane pump is real? Let us consider the squid giant axon. [since the work done on this cell was honored with a Nobel Prize (http://en.wikipedia.org/wiki/Squid_giant_axon), this axon and other similar preparations have become a favorite subject of numerous studies]. Remove its axoplasm to obtain the axon ghost (axon without axoplasm), then fill the axon ghost with natural or artificial seawater. The composition of the solution inside the axon will serve us as a reference point (the sodium and potassium concentrations in it will be the same as in the washing solutions). Now add ATP (and an ATP generating system, e.g. phosphoenolpyruvate plus pyruvate kinase) to the interior of the axon ghost and securely tie the ends of the axon so that its contents are not mixed with the external medium. Prepare a sufficient number of such ghosts, and take one axon after another at various time points to determine the ionic composition of their contents. Take the first axon after 10 minutes after the start of the experiment (analyze the contents, record the data), a second axon after 20 minutes, the third after an hour, and so on. If Na,K-ATPase does indeed function as the pump, the amount of Na+ in the axon ghost should gradually decrease, and K+ should increase. As a result of the experiment, we should obtain curves that clearly demonstrate the work of the membrane pump. Instead of experiments such as the one I have described, the literature is full of articles about the activity of Na,K-ATPase, how its activity can be changed, and how its activity affects membrane permeability and other properties. The authors of these articles have constructed a lot of graphs and created a mass of equations. But all of these are irrelevant to the experiment that I described above. In addition, there are many articles in the literature describing experiments along the following lines: the authors load lipid vesicles containing embedded Na,K-ATPase with Na+, with ATP or without ATP (control), and then separate the vesicles from the mother liquor. The result of such an experiment is normally: control vesicles (no ATP) contain lower Na+ than the experimental ones (with ATP). From this observation the authors conclude as a rule that the Na,K-ATPase in the presence of ATP acts as a pump and pumps sodium into the vesicles. However, can we consider such experiments as an evidence of the physiological pumping role of Na,K-ATPase? I think, not. The fact is that as soon as the vesicles are separated from the mother liquor, Na+ starts to leave them down the chemical potential gradient. The type of experiment discussed shows us only one thing: Na+ leaves control vesicles FASTER than vesicles with ATP. The authors of these studies explain this difference by the fact that in the presence of ATP, Na-K-ATPase works as a pump: sodium ions are initially pulled out of the vesicles and ATPase grabs them, and once again pumps them into the vesicles. However, there is another possible explanation: ATP, being a hydrophobic polyanion, interacts with the lipid membrane and changes its physical properties, affecting the properties of the Na,K-ATPase. As a result, the lipid membrane-Na,K-ATPase become LESS permeable to Na+ in the presence of ATP. If we really wish to examine the role of Na,K-ATPase as a "pump" we should adopt the negative hypothesis: Na,K-ATPase is not really a pump, but simply serves as a barrier to Na+ when it passes from the vesicles into the surrounding medium. To the best of my knowledge, nobody has checked such a counter-interpretation. If so, we have TWO possible explanations of the experiment with lipid vesicles. The existence of two explanations means the absence of proof. It is quite possible that there are other experimental approaches to proving Na,K-ATPase is a pump. It is important that we assume that the pumping function of Na-K-ATPase is not proven. If, however, an experimenter holds a priori the idea that Na,K-ATPase is a membrane pump, his experiments cannot be correct. As we well know, when we seek to prove something we must proceed by contradiction. Could you please give me even ONE reference with definitive proof of the pumping role of Na,K-ATPase? I cannot find it.

Some ideas described in "Protoreaction of Protoplasm" were developed in my recent article, "Native aggregation as a cause of origin of temporary cellular structures needed for all forms of cellular activity, signaling and transformations". Abstract According to the hypothesis explored in this paper, native aggregation is genetically controlled (programmed) reversible aggregation that occurs when interacting proteins form new temporary structures through highly specific interactions. It is assumed that Anfinsen's dogma may be extended to protein aggregation: composition and amino acid sequence determine not only the secondary and tertiary structure of single protein, but also the structure of protein aggregates (associates). Cell function is considered as a transition between two states (two states model), the resting state and state of activity (this applies to the cell as a whole and to its individual structures). In the resting state, the key proteins are found in the following inactive forms: natively unfolded and globular. When the cell is activated, secondary structures appear in natively unfolded proteins (including unfolded regions in other proteins), and globular proteins begin to melt and their secondary structures become available for interaction with the secondary structures of other proteins. These temporary secondary structures provide a means for highly specific interactions between proteins. As a result, native aggregation creates temporary structures necessary for cell activity."One of the principal objects of theoretical research in any department of knowledge is to find the point of view from which the subject appears in its greatest simplicity."Josiah Willard Gibbs (1839-1903). Full text: http://vladimirmatveev.ru

The battle of theories in cell physiology: http://ru.youtube.com/watch?v=cuvoGbD5h3g http://video.google.com/videoplay?docid=5738571587308679039

Faces of the History of Cell Biology. Music slide-show for Flash player. Download it [7.45 Mb]: http://www.yourfilehost.com/media.php?cat=other&file=Faces.of.the.History.of.Cell.Biology.rar

Dear GutZ, It is possible to ideate two situations. (i) Einstein theory with a lot of details, and (ii) a lot of details without the theory. Cell physiology, I think, has put in the second situation. What about this? The reference about membrane theory: http://www.bioparadigma.spb.ru/files/Ling-1997-Debunking.pdf

Membrane theory and the decline of scientific method V.V. Matveev and D.N. Wheatley. "Fathers" and "sons" of theories in cell physiology: the membrane theory. Cell. Mol. Biol., 51(8): 797-801, 2005. Abstract. The last 50 years in the history of life sciences are remarkable for a new important feature that looks as a great threat for their future. Aprofound specialization dominating in quickly developing fields of science causes a crisis of the scientific method. The essence of the method is a unity of two elements, the experimental data and the theory that explains them. To us, "fathers" of science, classically, were the creators of new ideas and theories. They were the true experts of their own theories. It is only they who have the right to say: "I am the theory". In other words, they were carriers of theories, of the theoretical knowledge. The fathers provided the necessary logical integrity to their theories, since theories in biology have still to be based on strict mathematical proofs. It is not true for sons. As a result of massive specialization, modern experts operate in very confined close spaces. They formulate particular rules far from the level of theory. The main theories of science are known to them only at the textbook level. Nowadays, nobody can say: "I am the theory". With whom, then is it possible to discuss today on a broader theoretical level? How can a classical theory - for example, the membrane one - be changed or even disproved under these conditions? How can the "sons" with their narrow education catch sight of membrane theory defects? As a result, "global" theories have few critics and control. Due to specialization, we have lost the ability to work at the experimental level of biology within the correct or appropriate theoretical context. The scientific method in its classic form is now being rapidly eroded. A good case can be made for "Membrane Theory", to which we will largely refer throughout this article. Find full text here: http://www.actomyosin.spb.ru/fathersandsons.htm The illustration for the article: http://www.bioparadigma.spb.ru/images/Fathers.and.Sons.jpg

PROTOREACTION OF PROTOPLASM INTRODUCTION According to an old Indian parable, well known in Russia, residents of the city of blind people asked several respected citizens to act as experts and to describe to them the nature of an elephant, about which they had heard much. It happened that one of these animals was present near the walls of their city. One expert who examined the elephant’s leg by feeling it came to the conclusion that the elephant was a column. Another expert, upon touching carefully the animal’s tail, stated that the elephant was a rope. The expert who got the tusk was absolutely sure that the elephant resembled a ploughshare. Clearly, the experts failed to agree and continued to dispute all their lives, since each one felt that their case was based firmly on established facts. Thus, each of them was in the right, but all of them were wrong on the whole. Cell physiology and the scientists dealing with study of this discipline somewhat remind us of the meaning of this parable. To some of them, cell physiology focuses on the plasma membrane, to others the nucleus is the key, yet others prefer seeing the key to the mysteries to be found in signaling pathways. The "touching" of individual cell parts continues in contemporary cell biology. Fortunately, the cell itself gives us examples of its reactions that imply the basis for generalizations, for a broad view of cell physiology. One such example is the universal cellular reaction (UCR) to external actions, which was studied in detail by the physiological school of the outstanding Russian scientist, Dmitrii Nasonov (1895-1957), founder of the Institute of Cytology of the Russian Academy of Sciences... This theme is continued in the article: Vladimir Matveev. Protoreaction of Protoplasm. Cell. Mol. Biol. 51(8): 715-723, 2005. See full text here: http://www.actomyosin.spb.ru/protoreaction.htm

CELL HYDROPHOBICITY: A MISSED ROLE FOR PROTEINS For a long time, and up to the present, the term hydrophobicity was mostly has been associated chiefly with lipids. The well-known Meyer-Overton rule was always a strong argument in favor of the lipid nature of biomembranes and of the membrane theory of anesthesia. Until the 1960s, to be "hydrophobic" was synonymous with being "lipid", and the hydrophobic properties of the cell were explained by the presence of its lipid membranes, first of all, and primarily the plasma membrane. Indeed, based on these concepts, numerous "lipid" theories of anesthesia were put forward. However, in the 1960s, when studying thermodynamic characteristics of the thermodynamics of protein folding and unfolding, Brandts (3) was the first to prove convincingly that during the folding of a protein molecule, hydrophobic areas are formed internally which are inaccessible to water. Initially the thermodynamics of conformational transitions in proteins was the subject of study by a small group of specialists. However, with time, it has become evident that hydrophobic areas within cells are represented not only by lipids, as this was thought for more than 70 years, but also by proteins. The importance of this reappraisal is emphasized by the fact that, after water, protein is the most abundant of all other constituents, comprising up to 65% of the dry mass of cells, and greatly exceeds the total amount of lipid. What I propose here is that the volume of the hydrophobic protein phase can greatly exceed that of the hydrophobic lipid phase. However, I also recognize that the full significance of this observation has not been understood and seemingly not accepted by contemporary cell physiologists in terms of paradigms and working hypotheses. This theme is continued in the article: Vladimir Matveev. Protoreaction of Protoplasm. Cell. Mol. Biol. 51(8): 715-723, 2005. See full text here: http://www.actomyosin.spb.ru/protoreaction.htm

Proteins normally include both hydrophobic and hydrophilic groups. See http://www.actomyosin.spb.ru/protoreaction.htm

Vladimir Matveev. Protoreaction of Protoplasm. Cell. Mol. Biol. 51(8): 715-723, 2005 Abstract. My goal is to describe briefly the universal cellular reaction (UCR) to external actions and agents. This general reaction was the main subject of investigation by the scientific school of the outstanding Russian cytologist, Dmitrii Nasonov (1895-1957). The UCR consists of two phases of complex changes in cellular viscosity and turbidity, in the cell's ability to bind vital dyes, in the resting membrane potential, and in cellular resistance to harmful actions. Works from the Nasonov School have shown that these changes are based on structural-functional transformations of many cell proteins that react uniformly to actions of different physical and chemical nature. In general, these complex changes do not depend on cell type, indicating the universal and ancient nature of the UCR as well as its general biological significance. A new interpretation of the mechanism of the universal reaction is proposed in this paper, and a possible role for contractile proteins in the mechanism of the UCR of muscle cells is presented. In addition, the concept of cell hydrophobicity is introduced. Nasonov's School proposed a concept of physiological standardization that allows comparison of data obtained by different investigators and that will also be described here. See full text here: http://www.actomyosin.spb.ru/protoreaction.htm

History of the Cell: http://www.discoveryofthecell.net/ Waddington (1968), for all his outstanding contributions to biology in the middle and later part of the 20th century, failed to mention the cell as a concept in his paper 'Main biological conceptions'. The cell to him was a reality, an object for investigation, a fact. Only such a fundamental notion can so present itself to one's consciousness that one considers it "something that goes without saying" - an objective phenomenon, like the sea or the stars. But the cell, a concept that took many years to emerge, was by no means an "obvious fact" to all concerned at the outset. The cell concept probably had a no less painful birth than many other concepts that now are considered fact, such as the heliocentric nature of our solar system (Galileo, 1612-32). That birth (not literally of the cell, but of the concept of the cell) has been the subject of much intensive research, compiled as one fascinating, highly erudite but complex treatise in Harris (2000). We might all concede that there is a "unit of life", and might be prepared to call it a cell, but there is no precise, unambiguous and generally agreed definition of "a cell".

FURTHER DETAILS ABOUT THE EVOLUTION At present it is commonly accepted that the most characteristic feature of the modern science is its marked specialization. Even researchers studying similar cellular structures - for instance, channels - live now in parallel worlds: those who study Na-channels do not see too much sense in communicating with those who study Ca-channels, and even less with those who study channels for organic molecules. Of course, expanding specialization is not merely a sensation or individual observations. We see everywhere objective evidence for degradation of sciences into individual "earldoms" whose autonomous status is constantly being enhanced. The most evident proof in favor for this is a rise of the number of publication co-authors, reaching in some cases up to several hundred names. Also steadily increasing are the numbers of specialized journals and conferences. The mean length of formulations of the essence of discoveries, for which Nobel Prizes are awarded, increases, while the number of "discoveries" decreases and their significance can be correctly evaluated by only an increasingly narrow circle of specialists. A decrease of significance of investigations on the background of a steady rise of the number of publications means that expenditures for science increase, while their true yield decreases. But whereas economic consequences of the specialization are widely discussed, the intellectual menace impending over science still escapes proper attention. The danger has descended over the Scientific Method itself. Theories of a general biological character were accepted many decades ago, and nowadays, due to the specialization, there are no scientists who master these theories so well as those who could be rightfully considered their bearers. As a result, the profound generalizations of the past have turned out to be outside the natural process of renovation, beyond criticism. If competing theories appear under these conditions, their significance and advantages over classical knowledge will be unable to be properly evaluated, fantastic as this might seem. There has appeared or can appear the situation when scientists mastering the most modern methods of investigations at the molecular level are guided in their work by obsolete or even erroneous concepts of the general character that they inherited from the classicism epoch. The theories of the past, instead of being always under scrutiny, have turned into the dogmas incompatible with the spirit of the scientific method. The extra specialization is a menace, which may lead to the loss of the integrity of scientific knowledge.

Themes for discussion can be found on the following sites: http://www.bioparadigma.spb.ru/hidden_history/ling_newbook.htm http://www.bioparadigma.spb.ru/revolution/contents.htm http://www.bioparadigma.spb.ru/reviewonpollack.htm http://www.bioparadigma.spb.ru/ling.htm http://www.bioparadigma.spb.ru/pollack.htm http://www.bioparadigma.spb.ru/edelmann.htm

Join Google Group "Cell Physiology and Biophysics" to discuss hidden problems of a theory of the living cell: http://groups-beta.google.com/group/Cell-Physiology/about Themes for discussion can be found on the following sites: http://www.bioparadigma.spb.ru/revolution/contents.htm'>http://www.bioparadigma.spb.ru/revolution/contents.htm http://www.bioparadigma.spb.ru/hidden_history/ling_newbook.htm'>http://www.bioparadigma.spb.ru/hidden_history/ling_newbook.htm http://www.bioparadigma.spb.ru/pollack.htm'>http://www.bioparadigma.spb.ru/pollack.htm Public website: http://www.bioparadigma.spb.ru There is the first therme for discussion in the group: EVOLUTION OF SCIENTIFIC METHOD The last 50 years in the history of life sciences are remarkable for a new important feature that looks as a great threat for their future. A profound specialization dominating in quickly developing fields of science causes a crisis of the scientific method. The essence of the method is a unity of two elements, the experimental data and the theory that explains them. To us, "fathers" of science, classically, were (are) the creators of new ideas and theories. They were the true experts of their own theories. It is only they who have the right to say: "I am the theory". In other words, they were carriers of theories, of the theoretical knowledge. The fathers provided the necessary logical integrity to their theories, since theories in biology have not still to be based on strict mathematical proofs. It is not true for sons. As a result of massive specialization, modern experts operate in very confined spaces. They formulate particular rules far from the level of theory. The main theories of science are known to them only at the textbook level. Nowadays, nobody can say: "I am the theory". With whom, then is it possible to discuss today on a broader theoretical level? How can a classical theory - for example, the membrane one - be changed or even disproved under these conditions? How can the "sons" with their narrow education catch sight of membrane theory defects? As a result, "global" theories have few critics and control. Due to specialization, we have lost the ability to work at the experimental level of biology within the correct or appropriate theoretical context. The scientific method in its classic form is now being rapidly eroded. Join our group!