scholarly journals Relevance of single cell and single molecule studies at different biological and physical length scales

Author(s):  
Wenfa Ng

Scale transcends multiple levels of biological and physical organization, and is the critical factor that determines success of any scientific investigation. Specifically, the scale at which a question is posed plays a crucial role in influencing the type of experiments and apparatuses needed. Single cell and single molecule experiments came to the fore of experiment science due to its capability at addressing a fundamental problem in biology and physical science: does the same behavior in cells and molecules transcend different length and population scales? Thus far, single cell experiments could be achieved with trapping of single cell using optical tweezer traps and microfluidic channels. The same, however, is not true for single molecule studies, which remains in the realm of theoretical and simulation studies. Specifically, single molecule experiment remains at the hundreds to thousands of molecules level, where possible skew in the population of molecules sampled could provide a false depiction of molecular reality of a larger population. But, what do scientists learn from single cell and single molecule studies? Is it the uncovering of mysteries of the probabilistic behavior at the single entity level, guided by perhaps quantum mechanics? The answer is no for single cell studies, given that cellular decision making require the input of tens to hundreds of molecular sensors and effectors within a cell. Hence, single cell behavior is not random, but directed at a nutrient or concentration gradient or signaling source. On the other hand, enzymatic catalysis of a single molecule substrate with the active site involves a quantum mechanical crosstalk. Thus, reaction between the substrate molecule and the active site proceeds if suitable energy levels (i.e., quantum mechanical states) are found for both parties. Given that distribution of quantum mechanical states is probabilistic, stochasticity rules single molecule interaction such as a covalent bond formation reaction between reactant A and B. Thus, single cell and single molecule studies do hold relevance in biological and physical sciences research if the correct experiment tool is used for a pertinent question at an appropriate length and population scale. For example, while tremendous amount of basic understanding could be derived from single cell experiments, single cell perspective is not relevant to questions examining the interactions between two large subpopulations of cells. Single molecule experiments, on the other hand, remains in the theoretical and simulation realm for highlighting the effect of quantum mechanics in guiding the behavior of molecules at the nanoscale.

2017 ◽  
Author(s):  
Wenfa Ng

Scale transcends multiple levels of biological and physical organization, and is the critical factor that determines success of any scientific investigation. Specifically, the scale at which a question is posed plays a crucial role in influencing the type of experiments and apparatuses needed. Single cell and single molecule experiments came to the fore of experiment science due to its capability at addressing a fundamental problem in biology and physical science: does the same behavior in cells and molecules transcend different length and population scales? Thus far, single cell experiments could be achieved with trapping of single cell using optical tweezer traps and microfluidic channels. The same, however, is not true for single molecule studies, which remains in the realm of theoretical and simulation studies. Specifically, single molecule experiment remains at the hundreds to thousands of molecules level, where possible skew in the population of molecules sampled could provide a false depiction of molecular reality of a larger population. But, what do scientists learn from single cell and single molecule studies? Is it the uncovering of mysteries of the probabilistic behavior at the single entity level, guided by perhaps quantum mechanics? The answer is no for single cell studies, given that cellular decision making require the input of tens to hundreds of molecular sensors and effectors within a cell. Hence, single cell behavior is not random, but directed at a nutrient or concentration gradient or signaling source. On the other hand, enzymatic catalysis of a single molecule substrate with the active site involves a quantum mechanical crosstalk. Thus, reaction between the substrate molecule and the active site proceeds if suitable energy levels (i.e., quantum mechanical states) are found for both parties. Given that distribution of quantum mechanical states is probabilistic, stochasticity rules single molecule interaction such as a covalent bond formation reaction between reactant A and B. Thus, single cell and single molecule studies do hold relevance in biological and physical sciences research if the correct experiment tool is used for a pertinent question at an appropriate length and population scale. For example, while tremendous amount of basic understanding could be derived from single cell experiments, single cell perspective is not relevant to questions examining the interactions between two large subpopulations of cells. Single molecule experiments, on the other hand, remains in the theoretical and simulation realm for highlighting the effect of quantum mechanics in guiding the behavior of molecules at the nanoscale.


Author(s):  
John von Neumann

This chapter returns to the analysis of quantum mechanical theories. In the previous chapter, how quantum mechanics makes possible the determination of all possible values of one particular physical quantity—energy—was only discussed. These values are the eigenvalues of the energy operator (i.e., the numbers of its spectrum). On the other hand, no mention was made about the values of other quantities, as well as regarding the causal or statistical relations among the values of several quantities. The statements of the theory relative to this problem are thus considered in this chapter. It takes as a basis the wave mechanical method of description since the equivalence of the two theories has already been established.


1987 ◽  
Vol 52 (9) ◽  
pp. 2194-2203
Author(s):  
Miloslav Kučera ◽  
Dušan Kimmer ◽  
Karla Majerová ◽  
Josef Majer

In the reaction of dianions with poly(methyl methacrylate), only an insignificant amount of insoluble crosslinked product is obtained. If, however, the concentration of grafting dianions approaches that of ester groups, the amount of poly(methyl methacrylate) which may thus be crosslinked becomes quite significant. Dications, too, can bring about crosslinking of only an insignificant number of poly(methyl methacrylate) chains. Carboxylic groups in poly(acrylic acid) react with dianions and dications in an anhydrous medium similarly to ester groups. On the other hand, in the presence of a cocatalytic amount of water dications are more readily bound to carboxylic groups, forming a covalent bond. The relatively highest efficiency was observed in the bond formation between dication and the poly[styrene-alt-(maleic anhydride)], both in an anhydrous medium and in the presence of H2O.


2020 ◽  
Vol 21 (18) ◽  
pp. 6510
Author(s):  
Alexandre A. de Castro ◽  
Daniel A. Polisel ◽  
Bruna T. L. Pereira ◽  
Elaine F. F. da Cunha ◽  
Kamil Kuca ◽  
...  

Organophosphorus (OP) compounds are used as both chemical weapons and pesticides. However, these agents are very dangerous and toxic to humans, animals, and the environment. Thus, investigations with reactivators have been deeply developed in order to design new antidotes with better efficiency, as well as a greater spectrum of action in the acetylcholinesterase (AChE) reactivation process. With that in mind, in this work, we investigated the behavior of trimedoxime toward the Mus musculus acetylcholinesterase (MmAChE) inhibited by a range of nerve agents, such as chemical weapons. From experimental assays, reactivation percentages were obtained for the reactivation of different AChE–OP complexes. On the other hand, theoretical calculations were performed to assess the differences in interaction modes and the reactivity of trimedoxime within the AChE active site. Comparing theoretical and experimental data, it is possible to notice that the oxime, in most cases, showed better reactivation percentages at higher concentrations, with the best result for the reactivation of the AChE–VX adduct. From this work, it was revealed that the mechanistic process contributes most to the oxime efficiency than the interaction in the site. In this way, this study is important to better understand the reactivation process through trimedoxime, contributing to the proposal of novel antidotes.


Molecules ◽  
2019 ◽  
Vol 24 (16) ◽  
pp. 2933 ◽  
Author(s):  
Ranajit Saha ◽  
Gourhari Jana ◽  
Sudip Pan ◽  
Gabriel Merino ◽  
Pratim Kumar Chattaraj

Noble gases (Ngs) are the least reactive elements in the periodic table towards chemical bond formation when compared with other elements because of their completely filled valence electronic configuration. Very often, extreme conditions like low temperatures, high pressures and very reactive reagents are required for them to form meaningful chemical bonds with other elements. In this personal account, we summarize our works to date on Ng complexes where we attempted to theoretically predict viable Ng complexes having strong bonding to synthesize them under close to ambient conditions. Our works cover three different types of Ng complexes, viz., non-insertion of NgXY type, insertion of XNgY type and Ng encapsulated cage complexes where X and Y can represent any atom or group of atoms. While the first category of Ng complexes can be thermochemically stable at a certain temperature depending on the strength of the Ng-X bond, the latter two categories are kinetically stable, and therefore, their viability and the corresponding conditions depend on the size of the activation barrier associated with the release of Ng atom(s). Our major focus was devoted to understand the bonding situation in these complexes by employing the available state-of-the-art theoretic tools like natural bond orbital, electron density, and energy decomposition analyses in combination with the natural orbital for chemical valence theory. Intriguingly, these three types of complexes represent three different types of bonding scenarios. In NgXY, the strength of the donor-acceptor Ng→XY interaction depends on the polarizing power of binding the X center to draw the rather rigid electron density of Ng towards itself, and sometimes involvement of such orbitals becomes large enough, particularly for heavier Ng elements, to consider them as covalent bonds. On the other hand, in most of the XNgY cases, Ng forms an electron-shared covalent bond with X while interacting electrostatically with Y representing itself as [XNg]+Y−. Nevertheless, in some of the rare cases like NCNgNSi, both the C-Ng and Ng-N bonds can be represented as electron-shared covalent bonds. On the other hand, a cage host is an excellent moiety to examine the limits that can be pushed to attain bonding between two Ng atoms (even for He) at high pressure. The confinement effect by a small cage-like B12N12 can even induce some covalent interaction within two He atoms in the He2@B12N12 complex.


2004 ◽  
Vol 32 (1) ◽  
pp. 41-45 ◽  
Author(s):  
S.A. McKinney ◽  
E. Tan ◽  
T.J. Wilson ◽  
M.K. Nahas ◽  
A.-C. Déclais ◽  
...  

Branched helical junctions are common in nucleic acids. In DNA, the four-way junction (Holliday junction) is an essential intermediate in homologous recombination and is a highly dynamic structure, capable of stacking conformer transitions and branch migration. Our single-molecule fluorescence studies provide unique insight into the energy landscape of Holliday junctions by visualizing these processes directly. In the hairpin ribozyme, an RNA four-way junction is an important structural element that enhances active-site formation by several orders of magnitude. Our single-molecule studies suggest a plausible mechanism for how the junction achieves this remarkable feat; the structural dynamics of the four-way junction bring about frequent contacts between the loops that are needed to form the active site. The most definitive evidence for this is the observation of three-state folding in single-hairpin ribozymes, the intermediate state of which is populated due to the intrinsic properties of the junction.


Quanta ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 68-87 ◽  
Author(s):  
Andrea Oldofredi ◽  
Michael Esfeld

Paul Dirac has been undoubtedly one of the central figures of the last century physics, contributing in several and remarkable ways to the development of quantum mechanics; he was also at the centre of an active community of physicists, with whom he had extensive interactions and correspondence. In particular, Dirac was in close contact with Bohr, Heisenberg and Pauli. For this reason, among others, Dirac is generally considered a supporter of the Copenhagen interpretation of quantum mechanics. Similarly, he was considered a physicist sympathetic with the positivistic attitude which shaped the development of quantum theory in the 1920s. Against this background, the aim of the present essay is twofold: on the one hand, we will argue that, analyzing specific examples taken from Dirac's published works, he can neither be considered a positivist nor a physicist methodologically guided by the observability doctrine. On the other hand, we will try to disentangle Dirac's figure from the mentioned Copenhagen interpretation, since in his long career he employed remarkably different—and often contradicting—methodological principles and philosophical perspectives with respect to those followed by the supporters of that interpretation.Quanta 2019; 8: 68–87.


2007 ◽  
Vol 05 (01n02) ◽  
pp. 157-167 ◽  
Author(s):  
THOMAS KESSEMEIER ◽  
THOMAS KRÜGER

Within the framework of a statistical interpretation of quantum mechanics, entanglement (in a mathematical sense) manifests itself in the non-separability of the statistical operator ρ representing the ensemble in question. In experiments, on the other hand, entanglement can be detected, in the form of non-locality, by the violation of Bell's inequality Δ ≤ 2. How can these different viewpoints be reconciled? We first show that (non-)separability follows different laws to (non-)locality, and, moreover, it is much more difficult to characterize as long as the mostly employed operational rather than an ontic definition of separability is used. In consequence, (i) "entanglement" has two different meanings which may or may not be realized simultaneously on one and the same ensemble, and (ii) we have to disadvise the use of the common separability definition which is still employed by the majority of the physical community.


2012 ◽  
Vol 27 (19) ◽  
pp. 1250102 ◽  
Author(s):  
TOSHIAKI TANAKA

We formulate [Formula: see text]-fold supersymmetry in quantum mechanical systems with reflection operators. As in the cases of other systems, they possess the two significant characters of [Formula: see text]-fold supersymmetry, namely, almost isospectrality and weak quasi-solvability. We construct explicitly the most general one- and two-fold supersymmetric quantum mechanical systems with reflections. In the case of [Formula: see text], we find that there are seven inequivalent such systems, three of which are characterized by three arbitrary functions having definite parity while the other four characterized by two arbitrary functions. In addition, four of the seven inequivalent systems do not reduce to ordinary quantum systems without reflections. Furthermore, in certain particular cases, they are essentially equivalent to the most general two-by-two Hermitian matrix two-fold supersymmetric quantum systems obtained previously by us.


1948 ◽  
Vol 135 (881) ◽  
pp. 430-446 ◽  
Author(s):  
Vincent Brian Wigglesworth

Insects live and feed, move, grow and multiply like other animals; but they are so varied in form, so rich in species, and adapted to such diverse conditions of life that they afford unrivalled opportunities for physiological study. The general problems of physiology are much the same in all groups of animals; and this lecture, which represents, in effect, an apology for the study of insect physi­ology, is an attempt to show that among the insects may be found material well suited for the solution of many of these problems. By human standards most insects are small in size, and this brings with it certain features which dominate their physiology. There is the same degree of functional specialization in their organs as there is in mammals; but they are made up of cells of the same dimensions as those in other animals—often, indeed, of cells which are larger than most. Each organ therefore contains far fewer cells, and the organization of their bodies must of necessity appear more simple. It is, however, a deceptive simplicity; for the range of physiological activities of which the single cell is capable is no less and may indeed be greater than it is in larger animals. On the other hand, their small size enables the insects to dispense with many of the physiological elaborations that are needed by mammals. Air-containing tracheae run direct to the tissues; and the high rates of metabolism which active insects develop can be met by the diffusion of gases along these tubes, supplemented in the most active forms by mechanical ventilation of the larger trunks or of the air sacs into which they are dilated.


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