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How can one measure group cohesion? From individual organisms to their interaction

Measuring atomic and molecular interactions was one of the main objectives of physics during the past century. It was an essential step not only in itself but because most macroscopic properties can be derived once one knows interaction strengths. At the present time, except for systems that can be described as discrete networks (like the Internet network) our knowledge of social and biological ties still remains very limited. An important step is to develop experimental means for measuring social and biological interactions. In this talk there are two parts. Firstly, we describe experimental evidence of inter-individual attraction in populations of insects. Secondly, we focus on a specific system, namely populations of Euglena gracilis, a green, swimming unicellular organism, for which we try to determine individual and interaction properties.

physics.bio-ph↗

Nanopore Sequencing of the phi X 174 genome

Nanopore sequencing of DNA is a single-molecule technique that may achieve long reads, low cost, and high speed with minimal sample preparation and instrumentation. Here, we build on recent progress with respect to nanopore resolution and DNA control to interpret the procession of ion current levels observed during the translocation of DNA through the pore MspA. As approximately four nucleotides affect the ion current of each level, we measured the ion current corresponding to all 256 four-nucleotide combinations (quadromers). This quadromer map is highly predictive of ion current levels of previously unmeasured sequences derived from the bacteriophage phi X 174 genome. Furthermore, we show nanopore sequencing reads of phi X 174 up to 4,500 bases in length that can be unambiguously aligned to the phi X 174 reference genome, and demonstrate proof-of-concept utility with respect to hybrid genome assembly and polymorphism detection. All methods and data are made fully available.

q-bio.GN↗

N-body Information Theory (NbIT) Analysis of Rigid-Body Dynamics in Intracellular Loop 2 of the 5-HT2A Receptor

Rigid-body motions of protein secondary structure are often implicated in mecha-nisms of protein function. In GPCRs, evidence suggests that intracellular loop 2 (IL2) contains a segment characterized as a helix when the activated receptor trig-gers downstream signaling. However, neither experimental nor computational methods are readily available to assess quantitatively the degree of collective mo-tions in such secondary structure motifs of proteins. Here we describe a new el-ement of our N-body Information Theory (NbIT) framework to address this problem. To this end we introduce total intercorrelation, a measure in infor-mation theory that can be used to describe n-body correlated dynamics between multivariate distributions, such as 3-dimensional atomic fluctuations in simula-tions of proteins. We also define two additional measures, the rigid-body fraction and correlation order, which can be determined from the decomposition of the configurational entropy. Using these measures, we analyze the dynamics of IL2 in microsecond Molecular Dynamics simulations of the 5-HT2A receptor to demonstrate the powerful features of the new analysis techniques in studying the collective motion dynamics of secondary structure motifs. The analysis reveals an intriguing difference in the extent of correlated motions in the helical segment of IL2 in the presence and absence of bound 5-HT, the endogenous agonist that ac-tivates the receptor and triggers downstream signaling, suggesting that IL2 rigid-body motions can display distinct behaviors that may discriminate functional mechanism of GPCRs.

q-bio.BM↗

Low-level laser irradiation-induced changes in bovine spermatozoa

Some biochemical and metabolic characteristics of bovine sperm cells irradiated with low-level laser were probed and correlated to the irradiation parameters. Bovine spermatozoa were exposed to spatially filtered light from a He-Ne laser (633 nm) with fluences from 150 to 600 mJ/cm2. General biochemical alterations were assessed by vibrational spectroscopy (micro-Fourier-Transform Infrared technique). The mitochondrial membrane potential was assessed by flow cytometry. Lipid peroxidation due to reactive oxygen species (ROS) production was assessed by thiobarbituric acid reactive substances (TBARS) assay. Sperm morphologic characteristics changes were probed by atomic force microscopy (AFM) technique. LLLI was able to induce, at different fluences, changes in lipid, DNA and protein contents. Moreover, LLLI also induced changes in TBARS production, suggesting an irradiation effect on lipid peroxidation. Acrosomal reaction induction evidences was found based on changes in protein structure (Amides I and II bands) and AFM characterization. The most interesting result, however, was the changes in methyl and DNA groups, which strongly suggests that LLLI can modify DNA methylation patterns, important for pregnancy establishment. The observed changes in the above-cited parameters have direct impact on sperm quality. The low-level laser irradiation has the potential to improve the fertilizing capacity of bovine sperm cells.

q-bio.TO↗

Scale-estimation of quantum coherent energy transport in multiple-minima systems

A generic and intuitive model for coherent energy transport in multiple minima systems coupled to a quantum mechanical bath is shown. Using a simple spin-boson system, we illustrate how a generic donor-acceptor system can be brought into resonance using a narrow band of vibrational modes, such that the transfer efficiency of an electron-hole pair (exciton) is made arbitrarily high. Coherent transport phenomena in nature are of renewed interest since the discovery that a photon captured by the light-harvesting complex (LHC) in photosynthetic organisms can be conveyed to a chemical reaction centre with near-perfect efficiency. Classical explanations of the transfer use stochastic diffusion to model the hopping motion of a photo-excited exciton. This accounts inadequately for the speed and efficiency of the energy transfer measured in a series of recent landmark experiments. Taking a quantum mechanical perspective can help capture the salient features of the efficient part of that transfer. To show the versatility of the model, we extend it to a multiple minima system comprising seven-sites, reminiscent of the widely studied Fenna-Matthews-Olson (FMO) light-harvesting complex. We show that an idealised transport model for multiple minima coupled to a narrow-band phonon can transport energy with arbitrarily high efficiency.

physics.bio-ph↗

From Intracellular Signaling to Population Oscillations: Bridging Scales in Collective Behavior

Collective behavior in cellular populations is coordinated by biochemical signaling networks within individual cells. Connecting the dynamics of these intracellular networks to the population phenomena they control poses a considerable challenge because of network complexity and our limited knowledge of kinetic parameters. However, from physical systems we know that behavioral changes in the individual constituents of a collectively-behaving system occur in a limited number of well-defined classes, and these can be described using simple models. Here we apply such an approach to the emergence of collective oscillations in cellular populations of the social amoeba Dictyostelium discoideum. Through direct tests of our model with quantitative in vivo measurements of single-cell and population signaling dynamics, we show how a simple model can effectively describe a complex molecular signaling network and its effects at multiple size and temporal scales. The model predicts novel noise-driven single-cell and population-level signaling phenomena that we then experimentally observe. Our results suggest that like physical systems, collective behavior in biology may be universal and described using simple mathematical models.

physics.bio-ph↗

Nanophotonics and DNA: New approaches

The aim of the present work is spectroscopic and thermodynamic study of DNA catalytic properties in the following processes: a) redox; b) formation of inter-strand cross-links; c) performing of photo-dynamic effects; d) nanoscale resonance radiationless electron excitation energy transfer. The most attention is paid to the latter, as truly nanoscale method in its origin. The nanoscale method of laser induced fluorescence resonance energy transfer (FRET) to donor (acridine orange) - acceptor (ethidium bromide) intercalator pair for quantitative and qualitative study of stability quality DNA double helix in solution in real time is offered. FRET method allows to estimate the concentration of double helix areas with high quality stability applicable for intercalation in DNA after it was subjected to stress effect. It gives the opportunity to compare various types of DNAs with 1) different origin; 2) various damage degrees; 3) being in various functional state. Alternative model and mechanisms of photodynamic effect on DNA in solutions are proposed. They are based on photoenergy degradation in solutions. The energy activates electrolytic dissociation of water molecules on H3O+ and OH- and acts as a catalyst for hydrolyse reactions of phosphordiester and glycoside linkages.

physics.bio-ph↗

Data Analysis for Time-Resolved QENS Experiments in Biophysics

To study the correlation between internal protein dynamics and protein functionality of bacteriorhodopsin, we have performed time-resolved quasielastic neutron scattering (QENS) experiments combined with in situ laser activation of protein function. A set of purple membrane samples with different lamellar lattice constants and, hence, different hydration levels has been examined at different time delays between the laser and neutron pulses. While the water content affected the lineshapes of QENS spectra, the laser-induced response remained constant within the accuracy of the method.

physics.bio-ph↗

Mechanical model of Golgi apparatus

The Golgi apparatus has intrigued researchers since its discovery and despite the advances, there are still many open questions in regards to its shape and function. Here, we propose a mechanical model of Golgi apparatus stack and explain its most elementary geometrical properties: the equilibrium number of cisternae, the stack size, and its general equilibrium shape. In order to gain comprehensive insight into the stack morphology, we combine both analytical and numerical methods. We successfully reconstruct the stack morphology using minimal assumptions, thus identifying the most dominant factors regulating the stack shape. We demonstrate that energy-wise the stack prefers an overall bent shape and show strong evidence that the adhesion strength determines the equilibrium number of cisternae per stack. We explore the morphological role of fenestrations and discuss their impact on the overall stack structure. We also comment on the effects of the membrane asymmetry on the shape of the cisternae and thus offer a broad steady-state study of the stack morphology and present a method that can be used also for other membrane-bound organelles.

physics.bio-ph↗

3D Object Imaging through Scattering Media

Human ability to visualize an image is usually hindered by optical scattering. Recent extensive studies have promoted imaging technique through turbid materials to a reality where color image can be restored behind scattering media in real time. The big challenge now is to recover a 3D object in a large field of view with depth resolving ability. Here, we reveal a new physical relationship between speckles generated from objects at different planes. With a single given point spread function, 3D imaging through scattering media is achieved even beyond the depth of field (DOF). Experimental testing of standard scattering media shows that the original DOF can be extended up to 5 times and the physical mechanism is depicted. This extended 3D imaging is expected to have important applications in science, technology, bio-medical, security and defense.

physics.optics↗

Detection Limit for Optically Sensing Specific Protein Interactions in Free-solution

Optical molecular sensing techniques are often limited by the refractive index change associated with the probed interactions. In this work, we present a closed form analytical model to estimate the magnitude of optical refractive index change arising from protein-protein interactions. The model, based on the Maxwell Garnett effective medium theory and first order chemical kinetics serves as a general framework for estimating the detection limits of optical sensing of molecular interactions. The model is applicable to situations where one interacting species is immobilized to a surface, as commonly done, or to emerging techniques such as Back-Scattering Interferometry (BSI) where both interacting species are un-tethered. Our findings from this model point to the strong role of as yet unidentified factors in the origin of the BSI signal resulting in significant deviation from linear optical response.

physics.app-ph↗

Functional optimality of the sulcus pattern of the human brain

We develop a mathematical model of information transmission across the biological neural network of the human brain. The overall function of the brain consists of the emergent processes resulting from the spread of information through the neural network. The capacity of the brain is therefore related to the rate at which it can transmit information through the neural network. The particular transmission model under consideration allows for information to be transmitted along multiple paths between points of the cortex. The resulting transmission rates are governed by potential theory. According to this theory, the brain has preferred and quantized transmission modes that correspond to eigenfunctions of the classical Steklov eigenvalue problem, with the reciprocal eigenvalues quantifying the corresponding transmission rates. We take the model as a basis for testing the hypothesis that the sulcus pattern of the human brain has evolved to maximize the rate of transmission of information between points in the cerebral cortex. We show that the introduction of sulci, or cuts, in an otherwise smooth domain indeed increases the overall transmission rate. We demonstrate this result by means of numerical experiments concerned with a spherical domain with a varying number of slits on its surface.

physics.bio-ph↗

Scanning Microwave Microscopy of Vital Mitochondria in Respiration Buffer

We demonstrate imaging using scanning microwave microscopy (SMM) of vital mitochondria in respiration buffer. The mitochondria are isolated from cultured HeLa cells and tethered to a solid graphene support. The mitochondria are kept vital (alive) using a respiration buffer, which provides nutrients to sustain the Krebs cycle. We verify that the mitochondria are "alive" by measuring the membrane potential using a voltage sensitive fluorescent dye (TMRE). The organelles are measured capacitively at 7 GHz. Several technical advances are demonstrated which enable this work: 1) The SMM operates in an electrophysiologically relevant liquid (hence conducting) environment; 2) The SMM operates in tapping mode, averaging the microwave reflection measurement over many tapping periods; 3) A tuned reflectometer enables increased sensitivity; 4) Variable frequencies up to 18 GHz are used; 5) In contrast with traditional matching/resonant methods that exhibit high quality factor that fail in the presence of liquids, interferometric/tuned reflectometer gives the possibility to adjust the quality factor or sensitivity even in the presence of the liquid.

physics.bio-ph↗

A generative model of realistic brain cells with application to numerical simulation of diffusion-weighted MR signal

In this work, we introduce a novel computational framework that we developed to use numerical simulations to investigate the complexity of brain tissue at a microscopic level with a detail never realised before. Directly inspired by the advances in computational neuroscience for modelling brain cells, we propose a generative model that enables us to simulate molecular diffusion within realistic digitalised brain cells, such as neurons and glia, in a completely controlled and flexible fashion. We validate our new approach by showing an excellent match between the morphology and simulated DW-MR signal of the generated digital model of brain cells and those of digital reconstruction of real brain cells from available open-access databases. We demonstrate the versatility and potentiality of the framework by showing a select set of examples of relevance for the DW-MR community. Further development is ongoing, which will support even more realistic conditions like dense packing of numerous 3D complex cell structures and varying cell surface permeability.

physics.med-ph↗

Sub-20 nm Nanopores Sculptured by a Single Nanosecond Laser Pulse

Single-molecule based 3rd generation DNA sequencing technologies have been explored with tremendous effort, among which nanopore sequencing is considered as one of the most promising to achieve the goal of $1,000 genome project towards personalized medicine. Solid state nanopore is consented to be complementary to protein nanopore and subjected to extensive investigations in the past decade. However, the prevailing solid-state nanopore preparation still relies on focused ion or electron beams, which are expensive and time consuming. Here we demonstrate the fabrication of nanopores down to 19 nm with a single nanosecond laser pulse. The laser drilling process is understood based upon a 2D axisymmetric transient heat transfer model, which predicts the laser fluence-dependent pore size distribution and shape with excellent agreement to electron microscopy and tomography analysis. As-drilled nanopore devices (26 nm) exhibit adequate sensitivity to detect single DNA molecule translocations and discriminate unfolded or folded events. Sub-10 nm nanopores can be readily achieved upon a thin layer of alumina deposition by atomic layer deposition, which further improves the DNA translocation signal to noise ratio considerably. Our work provides a solution for fast, low-cost and efficient large-scale fabrication of solid state nanopore devices for the 3rd generation nanopore sequencing.

physics.bio-ph↗

Electro-Neutral Models for dynamic Poisson-Nernst-Planck System: 2D Case

The Poisson-Nernst-Planck (PNP) system is a standard model for describing ion transport. In many applications, e.g., ions in biological tissues, the presence of thin boundary layers poses both modelling and computational challenges. In a previous paper, we derived simplified electro-neutral (EN) models in one dimensional space where the thin boundary layers are replaced by effective boundary conditions. In this paper, we extend our analysis to the two dimensional case where the EN model enjoys even greater advantages. First of all, it is much cheaper to solve the EN models numerically. Secondly, EN models are easier to deal with compared with the original PNP system, therefore it is also easier to derive macroscopic models for cellular structures using EN models. The multi-ion case with general boundary is considered, for a variety of boundary conditions including either Dirichlet or flux boundary conditions. Using systematic asymptotic analysis, we derive a variety of effective boundary conditions directly applicable to the EN system for the bulk region. To validate the EN models, numerical computations are carried out for both the EN and original PNP system, including the propagation of action potential for both myelinated and unmyelinated axons. Our results show that solving the EN models is much more efficient than the original PNP system.

physics.bio-ph↗

Coagulation model for ion channels in the lipid membranes

A two-dimensional (2D) model is developed to describe the growth of spotty patterns (domains) in the lipid membranes which result from the coagulation of ion channels. It is assumed that the ion channels can coagulate when activated, e.g. the neurotransmitter may act as the surface-active substance for some ion channels in the lipid matrix or the activation may result in increase of polarity of the ion channels that give rise to their coagulation process due to the Brownian diffusive motion. The results show that the domain radius rD of the ion channels scales with time as rD~time^0.4.The slowing and subsequent saturation of the domain radius at longer time periods are in qualitative agreement with experiments.

physics.bio-ph↗

It sounds like an action potential: unification of electrical, chemical and mechanical aspects of acoustic pulses in lipids

In an ongoing debate on the physical nature of the action potential, one group adheres to the electrical model of Hodgkin and Huxley, while the other describes the action potential as a non-linear acoustic pulse propagating within an interface near a transition. However, despite remarkable similarities, acoustics remains a non-intuitive mechanism for action potentials for the following reason. While acoustic pulses are typically associated with the propagation of density, pressure and temperature variation, action potentials are most commonly measured electrically. Here, we show that this discrepancy is lifted upon considering the electrical and chemical aspects of the interface, in addition to its mechanical properties. Specifically, we demonstrate how electrical and pH aspects of acoustic pulses emerge from an idealized description of the lipid interface, which is based on classical physical principles and contains no fit parameters. The pulses that emerge from the model show striking similarities to action potentials not only in qualitative shape and scales (time, velocity and voltage), but also demonstrate saturation of amplitude and annihilation upon collision.

physics.bio-ph↗