Controlling cell migration is important in tissue engineering and medicine. Cell motility depends on factors such as nutrient concentration gradients and soluble factor signaling. In particular, cell-cell signaling can depend on cell-cell separation distance and can influence cellular arrangements in bulk cultures. Here, we seek a physical-based approach, which identifies a potential governed by cell-cell signaling that induces a directed cell-cell motion. A single-cell barcode chip (SCBC) was used to experimentally interrogate secreted proteins in hundreds of isolated glioblastoma brain cancer cell pairs and to monitor their relative motions over time. We used these trajectories to identify a range of cell-cell separation distances where the signaling was most stable. We then used a thermodynamics-motivated analysis of secreted protein levels to characterize free-energy changes for different cell-cell distances. We show that glioblastoma cell-cell movement can be described as Brownian motion biased by cell-cell potential. To demonstrate that the free-energy potential as determined by the signaling is the driver of motion, we inhibited two proteins most involved in maintaining the free-energy gradient. Following inhibition, cell pairs showed an essentially random Brownian motion, similar to the case for untreated, isolated single cells.

An Ultrafast electronic excitation of N-2 in the vacuum ultraviolet creates a nonstationary coherent linear superposition of interacting valence and Rydberg states resulting in a net oscillating dipole moment. There is therefore a linear response to an electrical field that can be queried by varying the time delay between the pump and a second optical probe pulse. Both the pump and probe pulses are included in our computation as part of the Hamiltonian, and the time dependent wave function for both electronic and nuclear dynamics is computed using a grid representation for the internuclear coordinate. Even on an ultrafast time scale there are several processes that can be discerned beyond the expected coherence oscillations. In particular, the coupling between the excited valence and Rydberg states of the same symmetry is very evident and can be directly probed by varying the delay between pulse and. probe. For quite a number of vibrations the nuclear motion does not dephase the electronic disequilibrium. However, the nuclear motion does modulate the dipolar response by taking the wave packet in and out of the Franck-Condon region and by its strong influence on the coupling of the Rydberg and valence states. A distinct isotope effect arises from the dependence of the interstate coupling on the nuclear mass.

The quantum wave packet dynamics following a coherent electronic excitation of LiH by an ultrashort, polarized, strong one cycle infrared optical pulse is computed on several electronic states using a grid method. The coupling to the strong field of the pump and the probe pulses is included in the Hamiltonian used to solve the time-dependent Schrodinger equation. The polarization of the pump pulse allows us to control the localization in time and in space of the nonequilibrium coherent electronic motion and the subsequent nuclear dynamics. We show that transient absorption, resulting from the interaction of the total molecular dipole with the electric fields of the pump and the probe, is a very versatile probe of the different time scales of the vibronic dynamics. It allows probing both the ultrashort, femtosecond time scale of the electronic coherences as well as the longer dozens of femtoseconds time scales of the nuclear motion on the excited electronic states. The ultrafast beatings of the electronic coherences in space and in time are shown to be modulated by the different periods of the nuclear motion.

We describe a thermodynamic-motivated, information theoretic analysis of proteomic data collected from a series of 8 glioblastoma multiforme (GBM) tumors. GBMs are considered here as prototypes of heterogeneous cancers. That heterogeneity is viewed here as manifesting in different unbalanced biological processes that are associated with thermodynamic-like constraints. The analysis yields a molecular description of a stable steady state that is common across all tumors. It also resolves molecular descriptions of unbalanced processes that are shared by several tumors, such as hyperactivated phosphoprotein signaling networks. Further, it resolves unbalanced processes that provide unique classifiers of tumor subgroups. The results of the theoretical interpretation are compared against those of statistical multivariate methods and are shown to provide a superior level of resolution for identifying unbalanced processes in GBM tumors. The identification of specific constraints for each GBM tumor suggests tumor-specific combination therapies that may reverse this imbalance.

A single electron dynamic memory is designed based on the non-equilibrium dynamics of charge states in electrostatically defined metallic quantum dots. Using the orthodox theory for computing the transfer rates and a master equation, we model the dynamical response of devices consisting of a charge sensor coupled to either a single and or a double quantum dot subjected to a pulsed gate voltage. We show that transition rates between charge states in metallic quantum dots are characterized by an asymmetry that can be controlled by the gate voltage. This effect is more pronounced when the switching between charge states corresponds to a Markovian process involving electron transport through a chain of several quantum dots. By simulating the dynamics of electron transport we demonstrate that the quantum box operates as a finite-state machine that can be addressed by choosing suitable shapes and switching rates of the gate pulses. We further show that writing times in the ns range and retention memory times six orders of magnitude longer, in the ms range, can be achieved on the double quantum dot system using experimentally feasible parameters, thereby demonstrating that the device can operate as a dynamic single electron memory. Published by AIP Publishing.

Strong laser fields can be used to trigger an ultrafast molecular response that involves electronic excitation and ionization dynamics. Here, we report on the experimental control of the spatial localization of the electronic excitation in the C-60 fullerene exerted by an intense few-cycle (4 fs) pulse at 720 nm. The control is achieved by tailoring the carrier-envelope phase and the polarization of the laser pulse. We find that the maxima and minima of the photoemission-asymmetry parameter along the laser-polarization axis are synchronized with the localization of the coherent electronic wave packet at around the time of ionization.

Non-Boolean computations implementing operations on multi-valued variables beyond base 2 allow enhanced computational complexity. We introduce DNA as a functional material for ternary computing, and in particular demonstrate the use of three-valued oligonucleotide inputs to construct a 3 x 3 multiplication table. The system consists of two three-valued inputs of -1; 0; + 1 and a fluorophore/quencher functional hairpin acting as computational and reporter module. The interaction of the computational hairpin module with the different values of the inputs yields a 3 x 3 multiplication matrix consisting of nine nanostructures that are read out by three distinct fluorescence intensities. By combining three different hairpin computational modules, each modified with a different fluorophore/quencher pair, and using different sets of inputs, the parallel operation of three multiplication tables is demonstrated.

We propose that information processing can be implemented by measuring the directional components of the macroscopic polarization of an ensemble of molecules subject to a sequence of laser pulses. We describe the logic operation theoretically and demonstrate it by simulations. The measurement of integrated stimulated emission in different phase matching spatial directions provides a logic decomposition of a function that is the discrete analog of an integral transform. The logic operation is reversible and all the possible outputs are computed in parallel for all sets of possible multivalued inputs. The number of logic variables of the function is the number of laser pulses used in sequence. The logic function that is computed depends on the chosen chromophoric molecular complex and on its interactions with the solvent and on the two time intervals between the three pulses and the pulse strengths and polarizations. The outputs are the homodyne detected values of the polarization components that are measured in the allowed phase matching macroscopic directions, k(l), k(l) = Sigma(i) l(i) k(i) where k(i) is the propagation direction of the ith pulse and \l(i)\ is a set of integers that encodes the multivalued inputs. Parallelism is inherently implemented because all the partial polarizations that define the outputs are processed simultaneously. The outputs, which are read directly on the macroscopic level, can be multivalued because the high dynamical range of partial polarization measurements by nonlinear coherent spectroscopy allows for fine binning of the signals. The outputs are uniquely related to the inputs so that the logic is reversible. (C) 2015 AIP Publishing LLC.

Biomass composition of Chlamydomonas reinhardtii was studied during two consecutive cycles of 12 h light/12 h dark. As in our experimental conditions the two synchronized divisions were separated by 20 h, it was possible to show that accumulation of dry weight, proteins, chlorophyll and fatty acids mainly depends on cell division, whereas starch accumulation depends on a circadian rhythm as reported previously. Our metabolomics analyses also revealed that accumulation of five (Ser, Val, Leu, Ile and Thr) of the nine free amino acids detected displayed rhythmicity, depending on cell division while Glu was 20-50 times more abundant than the other ones probably because this free amino acid serves not only for protein synthesis but also for biosynthesis of nitrogen compounds. In addition, we performed a thermodynamic-motivated theoretical approach known as `surprisal analysis'. The results from this analysis showed that cells were close to a steady state all along the 48 h of the experiment. In addition, calculation of free energy of cellular metabolites showed that the transition point, i.e. the state which immediately precedes cell division, corresponds to the most unstable stage of the cell cycle and that division is identified as the greatest drop in the free energy of metabolites. (C) 2015 Elsevier B.V. All rights reserved.

Implementing parallel and multivalued logic operations at the molecular scale has the potential to improve the miniaturization and efficiency of a new generation of nanoscale computing devices. Two-dimensional photon-echo spectroscopy is capable of resolving dynamical pathways on electronic and vibrational molecular states. We experimentally demonstrate the implementation of molecular decision trees, logic operations where all possible values of inputs are processed in parallel and the outputs are read simultaneously, by probing the laser induced dynamics of populations and coherences in a rhodamine dye mounted on a short DNA duplex. The inputs are provided by the bilinear interactions between the molecule and the laser pulses, and the output values are read from the two-dimensional molecular response at specific frequencies. Our results highlights how ultrafast dynamics between multiple molecular states induced by light-matter interactions can be used as an advantage for performing complex logic operations in parallel, operations that are faster than electrical switching.

Experimental biology is providing the distribution of numerous different biological molecules inside cells and in body fluids of patients. Statistical methods of analysis have very successfully examined these rather large databases. We seek to use a thermodynamic analysis to provide a physical understanding and quantitative characterization of human cancers and other pathologies within a molecule-centered approach. The key technical development is the introduction of a Lagrangian. By imposing constraints the minimal value of the Lagrangian defines a thermodynamically stable state of the cellular system. The minimization also allows using experimental data measured at a number of different conditions to evaluate the steady-state distribution of biomolecules such as messenger RNAs. Thereby the number of effectively accessible quantum states of biomolecules is determined from the experimentally measured expression levels. With the increased resolution provided by the minimization of the Lagrangian one can differentiate between normal and diseased patients and further between disease subtypes. Each such refinement corresponds to imposing an additional constraint of biological origin. The constraints are the unbalanced ongoing biological processes in the system. MicroRNA expression level data for control and diseased lung cancer patients are analyzed as an example.

A dynamical simulation via a coupled-equation scheme that includes the ionization continua and field-induced effects describes a pump-probe experiment that monitors ultrafast electronic dynamics in LiH. The ionizing XUV attosecond pulse train that is included in the simulation is used as a frequency filter. By tuning the time interval between the attosecond pulses of the train to a beating frequency of the wave packet induced by the IR pump pulse we characterize the changing spatial localization from one end of the molecule to the other, reflecting the interferences of the nonstationary electronic density.

Scaffolding proteins play a central role in many regulatory cellular networks, where signalling proteins trigger different, and even orthogonal biological pathways. Such biological regulatory networks can be duplicated by multiplexer/demultiplexer logic operations. We present the use of libraries of Mg2+-dependent DNAzyme subunits as computational moduli for the construction of 2:1 and 4:1 multiplexers and a 1:2 demultiplexer. In the presence of the appropriate inputs, and the presence or absence of selector units, the guided assembly of the DNAzyme subunits to form active Mg2+-dependent DNAzyme proceeds. The formation of the active DNAzyme nanostructures is controlled by the energetics associated with the resulting duplexes between the inputs/selectors and the DNAzyme subunits. The library subunits are designed in such a way that, in the presence of the appropriate inputs/selectors, the inputs are knocked-down or triggered-on to yield the respective multiplexer/demultiplexer operations. Fluorescence is used as the readout for the outputs of the logic operations. The DNAzyme-based multiplexer/demultiplexer systems present biomolecular assemblies for data compression and decompression.

To understand how pairwise cellular interactions influence cellular architectures, we measured the levels of functional proteins associated with EGF receptor (EGFR) signaling in pairs of U87EGFR variant III oncogene receptor cells (U87EGFRvIII) at varying cell separations. Using a thermodynamics-derived approach we analyzed the cell-separation dependence of the signaling stability, and identified that the stable steady state of EGFR signaling exists when two U87EGFRvIII cells are separated by 80-100 mu m. This distance range was verified as the characteristic intercellular separation within bulk cell cultures. EGFR protein network signaling coordination for the U87EGFRvIII system was lowest at the stable state and most similar to isolated cell signaling. Measurements of cultures of less tumorigenic U87PTEN cells were then used to correctly predict that stable EGFR signaling occurs for those cells at smaller cell-cell separations. The intimate relationship between functional protein levels and cellular architectures explains the scattered nature of U87EGFRvIII cells relative to U87PTEN cells in glioblastoma multiforme tumors.

Quantum mechanical wavepacket dynamics simulation that includes the nuclear motion exhibit a prompt, few fs, dissociation of electronically attosecond excited N-2 in addition to the slow dissociation evident from spectral line broadening in well resolved spectra. The simulations show that nuclear motion can probe early times electron dynamics. The separation of time scales is mimicked by a model study fashioned like chemical kinetics of unimolecular dissociation. The physical origin of the separation into prompt and delayed decay is argued to be the same in the vibrational and the present case, namely that there are more bound than dissociative channels. (C) 2014 Published by Elsevier B.V.

A full dynamical simulation shows that the charge transfer between the amine and the phenyl moieties of the cation of the bifunctional molecule 2-phenylethyl-N,N-dimethylamine can be induced and subsequently probed by two ultrashort photoionizations. The first ionization of the pump-probe scheme is by a 1.5 fs UV or 6 fs IR pulse that ionizes the neutral. The pump pulse can be tailored to produce a coherent superposition of the electronic states of the cation that differ in their energy and spatial localization of their electron density. The time-dependent amplitudes of the states of the superposition means that the state of the cation is not stationary and we show that it is beating between the two ends of the molecule. This beating is next probed by a second attosecond XUV pulse. The ultrafast photoionization of the cation to the dication probes the spatial charge reorganization in the cation. We use the computed time-dependent molecular frame photoelectron angular distributions as a quantitative measure of the charge migration. The computation of the dynamics are carried out by a coupled equation scheme that includes an electronic manifold for the three charge states: neutral, cation and dication, the coupling to the ionization continua of the cation and the dication and the dynamics induced by the pump and the probe pulses.

Surprisal analysis is increasingly being applied for the examination of transcription levels in cellular processes, towards revealing inner network structures and predicting response. But to achieve its full potential, surprisal analysis should be integrated into a wider range computational tool. The purposes of this paper are to combine surprisal analysis with other important computation procedures, such as easy manipulation of the analysis results - e.g. to choose desirable result subsets for further inspection -, retrieval and comparison with relevant datasets from public databases, and flexible graphical displays for heuristic thinking. The whole set of computation procedures integrated into a single practical tool is what we call Computational Surprisal Analysis. This combined kind of analysis should facilitate significantly quantitative understanding of different cellular processes for researchers, including applications in proteomics and metabolomics. Beyond that, our vision is that Computational Surprisal Analysis has the potential to reach the status of a routine method of analysis for practitioners. The resolving power of Computational Surprisal Analysis is here demonstrated by its application to a variety of cellular cancer process transcription datasets, ours and from the literature. The results provide a compact biological picture of the thermodynamic significance of the leading gene expression phenotypes in every stage of the disease. For each transcript we characterize both its inherent steady state weight, its correlation with the other transcripts and its variation due to the disease. We present a dedicated website to facilitate the analysis for researchers and practitioners.