Cell motility as an entangled quantum coherence.

Cell motility underlying muscle contraction is imputed to a macroscopic quantum mechanical coherence actualized locally in the body of a biological organism. Actin-activated myosin ATPase activity functions as a heat sink operating effectively at an extremely low temperature. Extraction of heat energy from the actin filament can help condensing the atomic degrees of freedom constituting the filament into a macroscopic quantum state carrying a nonvanishing linear momentum. Sliding movement of an actin filament on myosin molecules while hydrolyzing ATP molecules is a consequence of the quantum mechanical coherence due to an extremely slow release of energy stored in an ATP molecule.     

Epigenetic regulation of glycosylation is the quantum mechanics of biology

Background

Most proteins are glycosylated, with glycans being integral structural and functional components of a glycoprotein. In contrast to polypeptides, which are fully encoded by the corresponding gene, glycans result from a dynamic interaction between the environment and a network of hundreds of genes.

Scope of review

Recent developments in glycomics, genomics and epigenomics are discussed in the context of an evolutionary advantage for higher eukaryotes over microorganisms, conferred by the complexity and adaptability which glycosylation adds to their proteome.

Major conclusions

Inter-individual variation of glycome composition in human population is large; glycome composition is affected by both genes and environment; epigenetic regulation of “glyco-genes” has been demonstrated; and several mechanisms for transgenerational inheritance of epigenetic marks have been documented.

General significance

Epigenetic recording of acquired characteristics and their transgenerational inheritance could be important mechanisms used by higher organisms to compete or collaborate with microorganisms.     

Chemical genetics: tailoring tools for cell biology

Chemical genetics is a research approach that uses small molecules as probes to study protein functions in cells or whole organisms. Here, I review the parallels between classical genetic and chemical-genetic approaches and discuss the merits of small molecules to dissect dynamic cellular processes. I then consider the pros and cons of different screening approaches and specify strategies aimed at identifying and validating cellular target proteins. Finally, I highlight the impact of chemical genetics on our current understanding of cell biology and its potential for the future.     

Forming and maintaining a heat engine for quantum biology

Chemical reactions upholding biological functions and structures are the process of measurement taking place among the participating chemical reactants. Chemical reactions occurring in thermal environments are either endothermic or exothermic. In particular, exothermic reactions that can live with temperature gradients of exogenous origin could potentially be competent enough to synthesize a robust quantum as a heat engine. Molecular organizations leading to the origin of the phenomenon of life might have been associated with the emergence of a quantum coherence embodied in a robust heat engine feeding on quantum decoherence. Evolutionary maintenance of a robust quantum heat engine, once appeared, can further be empowered by the build-up of temperature gradients of endogenous origin. Biology enriches the repertoire of quantum mechanics so as to include a robust heat engine as a legitimate member of a quantum in addition to the already established member of a quantum including an atom, molecule, and macromolecule.     

A note concerning quantum mechanics and medicine

The rapid growth of quantum mechanics in the twentieth century has in no small part been due to the advanced state of classical mechanics. The introduction of new mathematical concepts to biology and medicine, on the other hand, is difficult because of the absence of a strong mathematical foundation. As a result, in many instances, new theoretical approaches to biological material have depended upon the use of mechanical and electrical analogues. As this paper shows, from a solution to a mechanical problem by means of quantum mechanics comes a potentially useful approach to a common medical problem.     

Cell kinetics and radiation biology

The cell cycle, the growth fraction and cell loss influence the response of cells to radiation in many ways. The variation in radiosensitivity around the cell cycle, and the extent of radiation-induced delay in cell cycle progression have both been clearly demonstrated in vitro. This translates into a variable time of expression of radiation injury in different normal tissues, ranging from a few days in intestine to weeks, months or even years in slowly proliferating tissues like lung, kidney, bladder and spinal cord. The radiosensitivity of tumours, to single doses, is dominated by hypoxic cells which arise from the imbalance between tumour cell production and the proliferation and branching of the blood vessels needed to bring oxygen and other nutrients to each cell. The response to fractionated radiation schedules is also influenced by the cell kinetic parameters of the cells comprising each tissue or tumour. This is described in terms of repair, redistribution, reoxygenation and repopulation. Slowly cycling cells show much more curved underlying cell survival curves, leading to more dramatic changes with fractionation, dose rate or l.e.t. Rapidly cycling cells redistribute around the cell cycle when the cells in sensitive phases have been killed, and experience less mitotic delay than slowly proliferating cells. Reoxygenation seems more effective in tumours with rapidly cycling cells and high natural cell loss rates. Compensatory repopulation within a treatment schedule may spare skin and mucosa but does not spare slowly proliferating tissues. Furthermore, tumour cell proliferation during fractionated radiotherapy may be an important factor limiting the overall success of treatment.     

A stochastic model for leukocyte random motility and chemotaxis based on receptor binding fluctuations

Two central features of polymorphonuclear leukocyte chemosensory movement behavior demand fundamental theoretical understanding. In uniform concentrations of chemoattractant, these cells exhibit a persistent random walk, with a characteristic "persistence time" between significant changes in direction. In chemoattractant concentration gradients, they demonstrate a biased random walk, with an "orientation bias" characterizing the fraction of cells moving up the gradient. A coherent picture of cell movement responses to chemoattractant requires that both the persistence time and the orientation bias be explained within a unifying framework. In this paper, we offer the possibility that "noise" in the cellular signal perception/response mechanism can simultaneously account for these two key phenomena. In particular, we develop a stochastic mathematical model for cell locomotion based on kinetic fluctuations in chemoattractant/receptor binding. This model can simulate cell paths similar to those observed experimentally, under conditions of uniform chemoattractant concentrations as well as chemoattractant concentration gradients. Furthermore, this model can quantitatively predict both cell persistence time and dependence of orientation bias on gradient size. Thus, the concept of signal "noise" can quantitatively unify the major characteristics of leukocyte random motility and chemotaxis. The same level of noise large enough to account for the observed frequency of turning in uniform environments is simultaneously small enough to allow for the observed degree of directional bias in gradients.     

Combined quantum and molecular mechanics calculations on metalloproteins

The combination of quantum mechanics and molecular mechanics (QM/MM) methods is one of the most promising approaches to study the structure, function and properties of proteins. The number of QM/MM applications on metalloproteins is steadily increasing, especially studies with density functional methods on redox-active metal centres. Recent developments include new parameterised methods to treat covalent bonds between the quantum and classical systems, methods to obtain free energy from QM/MM results, and the combination of quantum chemistry and protein crystallography.     

Cell motility and the formation of lamellipodia

A report on work presented at the 39th Annual Meeting of the American Society for Cell Bilogy, Washington DC, December 11-15, 1999     

Cell signalling and motility in Entamoeba histolytica

Entamoeba histolytica crawls as a polarized cell following external stimuli, with the translocation of signals modifying extracellular matrix interactions and the amoeba cytoskeleton. Nancy Guillén here describes how the gliding of E. histolytica cells requires the activity of the actomyosin complex, and how actomyosin functions related to motility are necessary for pathogenesis and for amoebal escape from the host immune response.     

The thermodynamic principles of ligand binding in chromatography and biology

In chromatography, macromolecules do not adsorb in the traditional sense of the word but bind to ligands that are covalently bonded to the surface of the porous bead. Therefore, the adsorption must be modelled as a process where protein molecules bind to the immobilised ligands. The paper discusses the general thermodynamic principles of ligand binding. Models of the multi-component adsorption in ion-exchange and hydrophobic chromatography, HIC and RPLC, are developed. The parameters in the models have a well-defined physical significance. The models are compared to the Langmuir model. In the traditional adsorption models, the standard state Gibbs energy change of adsorption does not depend level of occupancy, but when it depends on the level of occupancy it gives rise to an adsorptive behaviour known as cooperativity. The binding of oxygen to haemoglobin is a well-known example from biology but it is also observed in chromatography due to protein-protein interactions. Retention measurements on beta-lactoglobulin A demonstrate this. A discussion of salt effects on hydrophobic interactions in precipitation and chromatography of proteins concludes the paper.     

Cell motility and local viscoelasticity of fibroblasts

Viscoelastic changes of the lamellipodial actin cytoskeleton are a fundamental element of cell motility. Thus, the correlation between the local viscoelastic properties of the lamellipodium (including the transitional region to the cell body) and the speed of lamellipodial extension is studied for normal and malignantly transformed fibroblasts. Using our atomic force microscopy-based microrheology technique, we found different mechanical properties between the lamellipodia of malignantly transformed fibroblasts (H-ras transformed and SV-T2 fibroblasts) and normal fibroblasts (BALB 3T3 fibroblasts). The average elastic constants, K, in the leading edge of SV-T2 fibroblasts (0.48 +/- 0.51 kPa) and of H-ras transformed fibroblasts (0.42 +/- 0.35 kPa) are significantly lower than that of BALB 3T3 fibroblasts (1.01 +/- 0.40 kPa). The analysis of time-lapse phase contrast images shows that the decrease in the elastic constant, K, for malignantly transformed fibroblasts is correlated with the enhanced motility of the lamellipodium. The measured mean speeds are 6.1 +/- 4.5 microm/h for BALB 3T3 fibroblasts, 13.1 +/- 5.2 microm/h for SV-T2 fibroblasts, and 26.2 +/- 11.5 microm/h for H-ras fibroblasts. Furthermore, the elastic constant, K, increases toward the cell body in many instances which coincide with an increase in actin filament density toward the cell body. The correlation between the enhanced motility and the decrease in viscoelastic moduli supports the Elastic Brownian Ratchet model for driving lamellipodia extension.