Poissonian Cellular Potts Models Reveal Nonequilibrium Kinetics of Cell Sorting.

Cellular Potts models are broadly applied across developmental biology and cancer research. We overcome limitations of the traditional approach, which reinterprets a modified Metropolis sampling as ad hoc dynamics, by introducing a physical timescale through Poissonian kinetics and by applying principles of stochastic thermodynamics to separate thermal and relaxation effects from athermal noise and nonconservative forces. Our method accurately describes cell-sorting dynamics in mouse-embryo development and identifies the distinct contributions of nonequilibrium processes, e.g., cell growth and active fluctuations.

Modeling Active Non-Markovian Oscillations.

Modeling noisy oscillations of active systems is one of the current challenges in physics and biology. Because the physical mechanisms of such processes are often difficult to identify, we propose a linear stochastic model driven by a non-Markovian bistable noise that is capable of generating self-sustained periodic oscillation. We derive analytical predictions for most relevant dynamical and thermodynamic properties of the model. This minimal model turns out to describe accurately bistablelike oscillatory motion of hair bundles in bullfrog sacculus, extracted from experimental data. Based on and in agreement with these data, we estimate the power required to sustain such active oscillations to be of the order of 100 k_{B}T per oscillation cycle.

[Proton transfer via the external proton channel of bacteriorhodopsin].

The process of proton transfer across the membrane via the external proton channel in bacteriorhodopsin is considered. A possible amino acid composition of the channel is suggested and the step-by-step mechanism of proton transfer is proposed which agrees with the experimental data. The rate of proton transfer between fixed centers at several chains of the channel was estimated for which the spectroscopic data are available.

A theoretical model for electron and proton coupling at quinone-binding site of photosystem II of higher plants.

In this work we consider the coupling of electron and proton transfer near Q(B) in the reaction center (RC) of photosystem II (PS2). We have carried out the calculations of the energy levels and proton density in the system Q(B)(-) Histidine L190. It is shown that the proton of the histidine forms the H-bond with twice-reduced Q(B)(2-). Based on these calculations, we propose a new explanation of the coupling between the electron and proton transfer.

[The submolecular mechanism of the initial stage of the electron coupling in the water oxidizing center of higher plants]. / Submolekuliarnyi mekhanizm nachal'nogo étapa sopriazheniia élektronnogo transporta v komplekse razlozheniia vody vysshikh rastenii.

The results of quantum chemistry calculations of the total energy and proton position in tyrosine-histidine system in a water-oxidizing complex are presented. On the basis of these calculations, the submolecular mechanism of the initial stage of the electron coupling was proposed.

[Initial stage of coupling electron and proton transport in the vicinity of the secondary quinone in photosynthesis of bacteria and plants]. / Nachal'nyi étap sopriazheniia élektronnogo i protonnogo transporta okolo vtorichnogo khinona v bakterial'nom i rastitel'nom fotosinteze.

The coupling of electron and proton transport in the vicinity of the secondary quinone QB in the reaction center of bacteria and photosystem II of higher plants was investigated. The energy levels and wave functions of the proton in the system QB--histidine L 190 were calculated. It was shown that the proton of histidine forms a hydrogen bond with the doubly reduced quinone QB2-. A new scheme of proton transport through histidine L 190 and its coupling with electron transport was proposed.

Vimentin is a novel AKT1 target mediating motility and invasion.

The PI3K/AKT signaling pathway is aberrant in a wide variety of cancers. Downstream effectors of AKT are involved in survival, growth and metabolic-related pathways. In contrast, contradictory data relating to AKT effects on cell motility and invasion, crucial prometastatic processes, have been reported pointing to a potential cell type and isoform type-specific AKT-driven function. By implication, study of AKT signaling should optimally be conducted in an appropriate intracellular environment. Prognosis in soft-tissue sarcoma (STS), the aggressive malignancies of mesenchymal origin, is poor, reflecting our modest ability to control metastasis, an effort hampered by lack of insight into molecular mechanisms driving STS progression and dissemination. We examined the impact of the cancer progression-relevant AKT pathway on the mesenchymal tumor cell internal milieu. We demonstrate that AKT1 activation induces STS cell motility and invasiveness at least partially through a novel interaction with the intermediate filament vimentin (Vim). The binding of AKT (tail region) to Vim (head region) results in Vim Ser39 phosphorylation enhancing the ability of Vim to induce motility and invasion while protecting Vim from caspase-induced proteolysis. Moreover, vimentin phosphorylation was shown to enhance tumor and metastasis growth in vivo. Insights into this mesenchymal-related molecular mechanism may facilitate the development of critically lacking therapeutic options for these devastating malignancies.