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arXiv2018

Application of the fluctuation theorem to motor proteins: from F1-ATPase to axonal cargo transport by kinesin and dynein

The fluctuation theorem is a representative theorem in non-equilibrium statistical physics actively studied in the 1990's. Relating to entropy production in non-equilibrium states, the theorem has been used to estimate the driving power of motor proteins from fluctuation in their motion. In this review, usage of the fluctuation theorem in experiments on motor proteins is illustrated for biologists, especially those who study mechanobiology, in which force measurement is a central issue. We first introduce the application of the fluctuation theorem in measuring the rotary torque of the rotary motor protein F1-ATPase. Next, as an extension of this application, a recent trial estimating the force generated during cargo transport in vivo by the microtubule motors kinesin and dynein is introduced. Elucidation of the physical mechanism of such transport is important, especially for neurons, in which deficits in cargo transport are deeply related to neuronal diseases. Finally, perspectives on the fluctuation theorem as a new technique in the field of neuroscience are discussed.

physics.bio-ph↗

arXiv2018

Non-associative learning in intra-cellular signaling networks

Nonlinear systems driven by recurrent signals are known to exhibit complex dynamical responses which, in the physiological context, can have important functional consequences. One of the simplest biological systems that is exposed to such repeated stimuli is the intra-cellular signaling network. In this paper we investigate the periodic activation of an evolutionarily conserved motif of this network, viz., the mitogen-activated protein kinase (MAPK) signaling cascade, with a train of pulses. The resulting response of the cascade, which shows integrative capability over several successive pulses, is characterized by complex adaptive behavior. These include aspects of non-associative learning, in particular, habituation and sensitization, which are observed in response to high- and low-frequency stimulation, respectively. In addition, the existence of a response threshold of the cascade, an apparent refractory behavior following stimulation with short inter-pulse interval, and an alternans-like response under certain conditions suggest an analogy with excitable media.

q-bio.SC↗

arXiv2018

Analytical and empirical measurement of fiber photometry signal volume in brain tissue

Fiber photometry permits monitoring fluorescent indicators of neural activity in behaving animals. Optical fibers are typically used to excite and collect fluorescence from genetically-encoded calcium indicators expressed by a subset of neurons in a circuit of interest. However, a quantitative understanding of the brain volumes from which signal is collected and how this depends on the properties of the optical fibers are lacking. Here we analytically model and experimentally measure the light emission and collection fields for optical fibers in solution and scattering tissue, providing a comprehensive characterization of fibers commonly employed for fiber photometry. Since photometry signals depend on both excitation and collection efficiency, a combined confocal/2-photon microscope was developed to evaluate these parameters independently. We find that the 80% of the effective signal arises from a 10^5-10^6 um3 volume extending ~200 um from the fiber face, and thus permitting a spatial interpretation of measurements made with fiber photometry.

physics.optics↗

arXiv2018

Microfluidic study of effects of flow velocity and nutrient concentration on biofilm accumulation and adhesive strength in a microchannel

Biofilm accumulation in the porous media can cause plugging and change many physical properties of porous media. Targeted bioplugging may have significant applications for industrial processes. A deeper understanding of the relative influences of hydrodynamic conditions including flow velocity and nutrient concentration, on biofilm growth and detachment is necessary to plan and analyze bioplugging experiments and field trials. The experimental results by means of microscopic imaging over a T-shape microchannel show that increase in fluid velocity could facilitate biofilm growth, but that above a velocity threshold, biofilm detachment and inhibition of biofilm formation due to high shear stress were observed. High nutrient concentration prompts the biofilm growth, but was accompanied by a relatively weak adhesive strength. This letter provides an overview of biofilm development in a hydrodynamic environment for better predicting and modelling the bioplugging associated with porous system in petroleum industry, hydrogeology, and water purification.

q-bio.CB↗

arXiv2018

Receptor-ligand rebinding kinetics in confinement

Rebinding kinetics of molecular ligands plays a critical role in biomachinery, from regulatory networks to protein transcription, and is also a key factor for designing drugs and high-precision biosensors.In this study, we investigate initial release and rebinding of ligands to their binding sites grafted on a planar surface, a situation commonly observed in single molecule experiments and which occurs during exocytosis in vivo. Via scaling arguments and molecular dynamic simulations, we analyze the dependence of non-equilibrium rebinding kinetics on two intrinsic length scales: average separation distance between the binding sites and dimensions of diffusion volume (e.g., height of the experimental reservoir in which diffusion takes place or average distance between receptor-bearing surfaces). We obtain time-dependent scaling laws for on rates and for the cumulative number of rebinding events for various regimes. Our analyses reveal that, for diffusion-limited cases, the on rate decreases via multiple power law regimes prior to the terminal steady-state regime, in which the on rate becomes constant. At intermediate times, at which particle density has not yet become uniform throughout the reservoir, the number of rebindings exhibits a distinct plateau regime due to the three dimensional escape process of ligands from their binding sites. The duration of this regime depends on the average separation distance between binding sites. Following the three-dimensional diffusive escape process, a one-dimensional diffusive regime describes on rates. In the reaction-limited scenario, ligands with higher affinity to their binding sites delay the power laws. Our results can be useful for extracting hidden time scales in experiments where kinetic rates for ligand-receptor interactions are measured in microchannels, as well as for cell signaling via diffusing molecules.

physics.bio-ph↗

arXiv2018

Ionic-heterogeneity-induced spiral- and scroll-wave turbulence in mathematical models of cardiac tissue

Spatial variations in the electrical properties of cardiac tissue can occur because of cardiac diseases. We introduce such gradients into mathematical models for cardiac tissue and then study, by extensive numerical simulations, their effects on reentrant electrical waves and their stability in both two and three dimensions. We explain the mechanism of spiral- and scroll-wave instability, which entails anisotropic thinning in the wavelength of the waves because of anisotropic variation in its electrical properties.

physics.bio-ph↗

arXiv2018

Disentangling co-occurrence patterns in n-partite ecosystems

The need to harmonise apparently irreconcilable arrangements in an ecosystem --nestedness and segregation-- has triggered so far different strategies. Methodological refinements, or the inclusion of behavioural preferences to the network dynamics offer a limited approach to the problem, since one remains constrained within a 2-dimensional view of an ecosystem, i.e. a presence-absence matrix. Here we question this partial-view paradigm, and show that nestedness and segregation may coexist across a varied range of scenarios. To do so, we rely on an upscaled representation of an ecological community as an $n$-partite hypergraph, inspired by Hutchinson's high-dimensional niche concept and the latest trends on ecological multilayer networks. This yields an inclusive description of an ecological system, for which we develop a natural extension of the definition of nestedness to larger dimensional spaces, revealing how competitive exclusion may operate regardless of a highly nested bipartite system.

physics.soc-ph↗

arXiv2021

Small-misorientation toughness in biominerals evolved convergently

The hardest materials in living organisms are biologically grown crystalline minerals, or biominerals, which are also incredibly fracture-tough. Biomineral mesostructure includes size, shape, spatial arrangement, and crystal orientation of crystallites, observable at the mesoscale (10 nanometer - 10 micron). Here we show that diverse biominerals, including nacre and prisms from mollusk shells, coral skeletons, and tunicate spicules have different mesostructures, but they converged to similar, small (<30 degrees) misorientations of adjacent crystals at the mesoscale. We show that such small misorientations are an effective toughening mechanism. Combining Polarization-dependent Imaging Contrast (PIC) mapping of mesostructures and Molecular Dynamics (MD) simulations of misoriented bicrystals, we reveal here that small misorientations toughen bicrystals, thus explaining why they evolved independently but convergently: preventing fracture is a clear evolutionary advantage for diverse organisms.

physics.bio-ph↗

arXiv2022

Effect of Cu(II), Pb(II), Mg(II) ions on gamma-irradiated Spirulina platensis

Influence of metal ions Cu(II), Pb(II), Mg(II) on Spirulina platensis cells were studied after three times Cs137 gamma irradiation discrete dose (in each case 20 kGy irradiation dose) and recultivation using UV-VIS spectrometry. It was shown, that metal ions Mg(II), Pb(II), Cu(II) differ from each other in terms of interaction efficiency. In particular, Mg(II) ions act as a stimulant to increase content for Spirulina platensis components after several times with discrete doses of radiation and cultivation . For Pb (II) ions, the change in absorption intensity at low concentrations slowly decreases, and then with an increase in the Pb (II) concentration, the absorption intensity increases for C-phycocyanin, Ch1a, which implies an increase in the quantity content of Spirulina platensis constituents. Such effect for Cu(II) not observed.

physics.bio-ph↗

arXiv2022

Cr (VI) biosorption at different Na (I) concentrations after Zn(II) uptake during Arthrobacter species growth

The biosorption of Cr(VI) Arthrobacter species (Arthrobacter globiformis 151B and Arthrobacter oxides 61B) after growth in the presence of Zn (II) ions at different Na (I) concentrations was studied application using dialysis and atomic absorption analysis. It was shown that after absorption of Zn(II) during growth of types of Arthrobacter the biosorption of Cr (VI) with types Arthrobacter (Arthrobacter globiformis 151B, Arthrobacter oxidas 61B) increases at various concentration of Na (I) comparative without Zn(II), at identical concentration of Na (I). It is seen, that zinc(II) ions promote for Cr(VI) part of the active centers of Arthrobacter species and Na(I) ions already has relatively little effect on them. However, this change is more pronounced for Cr (VI) _Arthrobacter globiformis 151B + Zn (II) than for Cr (VI) _Arthrobacter oxides of 61B + Zn (II).

physics.bio-ph↗

arXiv2022

Tissue fluidization by cell-shape-controlled active stresses

Biological cells can actively tune their intracellular architecture according to their overall shape. Here we explore the rheological implication of such coupling in a minimal model of a dense cellular material where each cell exerts an active mechanical stress along its axis of elongation. Increasing the active stress amplitude leads to several transitions. An initially hexagonal crystal motif is first destabilized into a solid with anisotropic cells. Increasing activity further, we find a re-entrant transition to a regime with finite hexatic order and finite shear modulus, in which cells arrange according to a rhombile pattern with periodically arranged rosette structures. The shear modulus vanishes again at a third threshold beyond which spontaneous tissue flows arise. In this last regime, we observe the emergence of cell shape patterns called topological defects, with flow and stress fields around defects agreeing with those observed in epithelial tissue experiments. We further provide a testable prediction of cell-cell rearrangement hotspots near topological defects. Overall, our work connects seemingly distinct features - e.g. rosettes and topological defects - observed across various types of epithelial tissues.

cond-mat.soft↗

arXiv2024

Spatio-Temporal Instabilities of Blood Flow in a Model Capillary Network

We present experimental evidence of multiple blood flow configurations in a relatively simple microfluidic network under constant inlet conditions. We provide evidence of multistability and unsteady dynamics and find good agreement with a theoretical {one-dimensional advection} model for blood flow in microvascular networks{ that relies on the widely used laws for rheology and phase separation}. We discuss the ramifications for microfluidic experiments and measurements using blood and implications for in vivo microcirculation. Our findings suggest that further modeling in microvascular networks should discard the usual assumption of unique, steady-state flow solutions, with crucial consequences regarding gas, nutrient, and waste transport.

physics.flu-dyn↗

arXiv2026

An interdimensional funnel enhances topologically protected oscillations in high-dimensional stochastic systems

Biochemical systems such as protein complexes often occupy configuration spaces whose dimensionality grows with the number of molecular components. Although usually viewed as an obstacle to coherent dynamics, here we show that high dimensionality can enhance topologically protected oscillations. In the topological regime, a stochastic system with a $D$-dimensional configuration space develops a steady-state current confined to a one-dimensional edge cycle. The intervening boundary faces between the $D$-dimensional bulk and the one-dimensional cycle form an interdimensional funnel, sequentially pushing the system towards lower dimensional faces, down to the one-dimensional cycle. As a consequence, increasing $D$ enhances the funnel, leading to improved one-dimensional localization and oscillatory coherence. A quantized biorthogonal Zak phase identifies the transition to the topological regime, which additionally exhibits a highly structured non-Hermitian skin effect. In contrast with previous realizations of topological states in stochastic systems, the phenomena we uncover have no counterpart in quantum condensed matter or active matter systems.

cond-mat.soft↗

arXiv2013

Metabolizable Bi2Se3 Nanoplates: Biodistribution, Toxicity, and Uses for Cancer Radiation Therapy and Imaging

Bi, a high atom number element, has a high photoelectric absorption coefficient, and Se element has anticancer activity. Hence, their compound chalcogenide (Bi2Se3) deserves a thorough investigation for biomedical applications. This study reveals that Bi2Se3 nanoplates (54 nm wide) protected with poly(vinylpyrollidone) (PVP) are biocompatible and have low toxicity even at a high dose of 20 mg/kg in mice. This conclusion was made through the studies on the biodistribution and 90-day long term in vivo clearance of the nanoplates. Liver and spleen were dominant organs for the nanoplates accumulation which was mainly due to RES absorption, but 93 % the nanoplates were cleared after 90 days treatment. Concentrations of Bi and Se in tumor tissue continuously increased until 72 h after intraperitoneal injection into mice. Such selective accumulation of Bi was utilized to enhance the contrast of X-ray CT images. The Bi elements concentrated in a tumor led to damage on the tumor cells when exposed to gamma radiation. Growth of the tumor significantly delayed and stopped after 16 days after the tumor was treated with the Bi2Se3 nanoplates and radiation. This work clearly shows that the Bi2Se3 nanoplates may be used for cancer radiation therapy and CT imaging. They deserve further studies for biological and medical applications.

physics.bio-ph↗

arXiv2013

Enhanced Tumor Accumulation of Sub-2 nm Gold Nanoclusters for Cancer Radiation Therapy

A new type of metabolizable and efficient radiosensitizer for cancer radiotherapy is presented in this study by combining ultrasmall Au nanoclusters (NCs, <2 nm) with biocompatible coating ligands (glutathione, GSH). The new nano-construct (GSH-coated Au25 NCs) inherits attractive features of both the Au core (strong radiosensitizing effect) and GSH shell (good biocompatibility). It can preferentially accumulate in tumor via the improved EPR effect, which leads to strong enhancement for cancer radiotherapy. After the treatment, the small-sized GSH-Au25 NCs can be efficiently cleared by the kidney, minimizing any potential side effects due to the accumulation of Au25 NCs in the body.

physics.bio-ph↗

arXiv2013

The Fluctuations of Blocked Ionic Current Reveal the Instantaneous Statuses of DNA in Graphene Nanopore

Extracting the sequence information of DNA from the blocked ionic current is the crucial step of the ionic current-based nanopore sequencing approaches. The thinnest graphene nanopore, which contained only one layer of carbon atoms, potentially has ultra-high DNA sequencing sensitivity. However, the dynamical translocation information of DNA contained in the blocked ionic current has not been well understood to date. In this letter, an assessment to the sensitivity of ionic current-based graphene nanopore DNA sensing approach was carried out using molecular dynamics simulations. By filtering the molecular thermal motion induced noise of ionic current, we found that the instantaneous conformational variations of DNA in graphene nanopore could be revealed from the fluctuations of the denoised ionic current. However, the blockage of ionic current which induced by the proximity of the DNA base-pairs to the nanopore (within 1.5 nm) was also observed. Although the expected single-base resolution of graphene nanopore should be enhanced by further studies, our findings indicated that the ionic current-based graphene nanopore sensing approach has high sensitivity to the instantaneous translocation status of DNA.

physics.bio-ph↗

arXiv2011

Exact and efficient calculation of Lagrange multipliers in constrained biological polymers: Proteins and nucleic acids as example cases

In order to accelerate molecular dynamics simulations, it is very common to impose holonomic constraints on their hardest degrees of freedom. In this way, the time step used to integrate the equations of motion can be increased, thus allowing, in principle, to reach longer total simulation times. The imposition of such constraints results in an aditional set of Nc equations (the equations of constraint) and unknowns (their associated Lagrange multipliers), that must be solved in one way or another at each time step of the dynamics. In this work it is shown that, due to the essentially linear structure of typical biological polymers, such as nucleic acids or proteins, the algebraic equations that need to be solved involve a matrix which is banded if the constraints are indexed in a clever way. This allows to obtain the Lagrange multipliers through a non-iterative procedure, which can be considered exact up to machine precision, and which takes O(Nc) operations, instead of the usual O(Nc3) for generic molecular systems. We develop the formalism, and describe the appropriate indexing for a number of model molecules and also for alkanes, proteins and DNA. Finally, we provide a numerical example of the technique in a series of polyalanine peptides of different lengths using the AMBER molecular dynamics package.

physics.bio-ph↗

arXiv2013

Imaging material properties of biological samples with a Force Feedback Microscope

Mechanical properties of biological samples have been imaged with a \textit{Force Feedback Microscope}. Force, force gradient and dissipation are measured simultaneously and quantitatively, merely knowing the AFM cantilever spring constant. Our first results demonstrate that this robust method provides quantitative high resolution force measurements of the interaction The little oscillation imposed to the cantilever and the small value of its stiffness result in a vibrational energy much smaller than the thermal energy, reducing the interaction with the sample to a minimum. We show that the observed mechanical properties of the sample depend on the force applied by the tip and consequently on the sample indentation. Moreover, the frequency of the excitation imposed to the cantilever can be chosen arbitrarily, opening the way to frequency-dependent studies in biomechanics, sort of spectroscopic AFM investigations.

physics.bio-ph↗