General Physical Mechanism Research Articles

A cooperative relaxation model with two physical parameters for investigating the temperature and cure dependence of relaxation mechanisms in resins

Modeling the relaxation properties of resin matrix during cure plays an important role in predicting process-induced residual stresses and final distortions of resin-based composites. This paper develops a physical characterization model, which explains the temperature and cure-degree dependence of relaxation behaviors in terms of the size of cooperatively rearranging region, and special emphasis is placed on investigating the general physical mechanism of cure degree affecting the relaxation properties. In this model, the relaxation time is governed by a modified Adam-Gibbs equation, which is extended here to include the cure dependence. In addition, the relaxation modulus is modeled in a chemo-rheologically simple manner (CSM) based on the free volume theory. Material characterization is carried out using experimental data of two typical resins. It is shown that two cure-dependent model parameters, i.e., the smallest size of the cooperatively rearranging region and the glass transition temperature, are sufficient in accounting for the effect of cure on the relaxation modulus, and could provide a physical explanation of the influence of cure on relaxation behaviors. Furthermore, the proposed model is numerically realized by incorporating ABAQUS with UMAT subroutine, and its validity in predicting the residual stresses and final distortion of composites is also numerically verified by comparing with the results available in literature.

Nonequilibrium steady state of trapped active particles.

We consider an overdamped particle with a general physical mechanism that creates noisy active movement (e.g., a run-and-tumble particle or active Brownian particle, etc.), that is confined by an external potential. Focusing on the limit in which the correlation time τ of the active noise is small, we find the nonequilibrium steady-state distribution P_{st}(X) of the particle's position X. While typical fluctuations of X follow a Boltzmann distribution with an effective temperature that is not difficult to find, the tails of P_{st}(X) deviate from a Boltzmann behavior: In the limit τ→0, they scale as P_{st}(X)∼e^{-s(X)/τ}. We calculate the large-deviation function s(X) exactly for arbitrary trapping potential and active noise in dimension d=1, by relating it to the rate function that describes large deviations of the position of the same active particle in absence of an external potential at long times. We then extend our results to d>1 assuming rotational symmetry.

A diffusiophoretic mechanism for ATP-driven transport without motor proteins

The healthy growth and maintenance of a biological system depends on the precise spatial organization of molecules within the cell through the dissipation of energy. Reaction–diffusion mechanisms can facilitate this organization, as can directional cargo transport orchestrated by motor proteins, by relying on specific protein interactions. However, transport of material through the cell can also be achieved by active processes based on non-specific, purely physical mechanisms, a phenomenon that remains poorly explored. Here, using a combined experimental and theoretical approach, we discover and describe a hidden function of the Escherichia coli MinDE protein system: in addition to forming dynamic patterns, this system accomplishes the directional active transport of functionally unrelated cargo on membranes. Remarkably, this mechanism enables the sorting of diffusive objects according to their effective size, as evidenced using modular DNA origami–streptavidin nanostructures. We show that the diffusive fluxes of MinDE and non-specific cargo couple via density-dependent friction. This non-specific process constitutes a diffusiophoretic mechanism, as yet unknown in a cell biology setting. This nonlinear coupling between diffusive fluxes could represent a generic physical mechanism for establishing intracellular organization.

Mechanism for Strong Chimeras.

Chimera states have attracted significant attention as symmetry-broken states exhibiting the unexpected coexistence of coherence and incoherence. Despite the valuable insights gained from analyzing specific systems, an understanding of the general physical mechanism underlying the emergence of chimeras is still lacking. Here, we show that many stable chimeras arise because coherence in part of the system is sustained by incoherence in the rest of the system. This mechanism may be regarded as a deterministic analog of noise-induced synchronization and is shown to underlie the emergence of strong chimeras. These are chimera states whose coherent domain is formed by identically synchronized oscillators. Recognizing this mechanism offers a new meaning to the interpretation that chimeras are a natural link between coherence and incoherence.

A multiple therapy hypothesis for treatment of COVID-19 patients

The coronavirus disease 2019 (COVID-19) pandemic, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has killed more than one million people as of October 1, 2020. Consequently, a search is on for a treatment that can bring the pandemic to an end. However, treatments (vaccine, antiviral, plasma) that are directed at specific viral proteins (RNA polymerase, spike proteins) may not work well against all strains of the virus. Therefore, it is hypothesized that a therapy based on multiple treatments is needed for COVID-19 patients and to bring the pandemic to an end. Here, it is proposed that a combination of cool air therapy (CAT) and purified air technology (PAT) in an oxygen species cool air respirator (OSCAR) could be used to reduce viral (SARS-CoV-2) load and severity of illness in COVID-19 patients through the individual dose–response relationship. In addition, the proposed therapy (CAT + PAT in OSCAR), which works by a more general physical and chemical mechanism, should work well with other treatments (vaccine, antiviral, plasma) that target specific viral proteins (RNA polymerase, spike proteins) to provide a safe and effective multiple therapy approach for ending the COVID-19 pandemic caused by SARS-CoV-2.

Polymer Modelling Predicts Chromosome Reorganisation in Senescence

Lamina-associated domains (LADs) cover a large part of the human genome and are thought to play a major role in shaping the nuclear architectural landscape. Here, we perform polymer simulations, microscopy and mass spectrometry to dissect the roles played by heterochromatin- and lamina-mediated interactions in nuclear organisation. Our model explains the conventional organisation of heterochromatin and euchromatin in growing cells and the pathological organisation found in oncogene-induced senescence and progeria. We show that the experimentally observed changes in the locality of contacts in senescent and progeroid cells can be explained as arising due to phase transitions in the system. Within our simulations LADs are highly stochastic, as in experiments. Our model suggests that, once established, the senescent phenotype should be metastable even if lamina-mediated interactions were reinstated. Overall, our simulations uncover a generic physical mechanism that can regulate heterochromatin segregation and LAD formation in a wide range of mammalian nuclei.

Giant Conductance Enhancement of Intramolecular Circuits through Interchannel Gating

Summary For neutral intramolecular circuits with two constitutionally identical branches, a maximum 4-fold increase in total conductance can be obtained according to constructive quantum interference (CQI). For charged intramolecular circuits, however, the strong electrostatic interactions entangle the quantum states of these two parallel pathways, thus introducing complicated transport behavior that warrants experimental investigation of the intramolecular circuit rules. Here, we report that a tetracationic cyclophane with parallel channels exhibits a 50-fold conductance enhancement compared with that of a single-channel control, an observation that supplements intramolecular circuit law in systems with strong Coulombic interactions. Flicker noise measurements and theoretical calculations show that strong electrostatic interactions between charged parallel channels—serving as the chemical gate to promote the effective conductance of each channel—and CQI boosts the total conductance of the two-channel circuit. The molecular design presented herein constitutes a proof-of-principle approach to charged intramolecular circuits that are desirable for quantum circuits and devices.

Changes in ESCRT-III filament geometry drive membrane remodelling and fission in silico

BackgroundESCRT-III is a membrane remodelling filament with the unique ability to cut membranes from the inside of the membrane neck. It is essential for the final stage of cell division, the formation of vesicles, the release of viruses, and membrane repair. Distinct from other cytoskeletal filaments, ESCRT-III filaments do not consume energy themselves, but work in conjunction with another ATP-consuming complex. Despite rapid progress in describing the cell biology of ESCRT-III, we lack an understanding of the physical mechanisms behind its force production and membrane remodelling.ResultsHere we present a minimal coarse-grained model that captures all the experimentally reported cases of ESCRT-III driven membrane sculpting, including the formation of downward and upward cones and tubules. This model suggests that a change in the geometry of membrane bound ESCRT-III filaments—from a flat spiral to a 3D helix—drives membrane deformation. We then show that such repetitive filament geometry transitions can induce the fission of cargo-containing vesicles.ConclusionsOur model provides a general physical mechanism that explains the full range of ESCRT-III-dependent membrane remodelling and scission events observed in cells. This mechanism for filament force production is distinct from the mechanisms described for other cytoskeletal elements discovered so far. The mechanistic principles revealed here suggest new ways of manipulating ESCRT-III-driven processes in cells and could be used to guide the engineering of synthetic membrane-sculpting systems.

Polymer Modeling Predicts Chromosome Reorganization in Senescence

SummaryLamina-associated domains (LADs) cover a large part of the human genome and are thought to play a major role in shaping the nuclear architectural landscape. Here, we perform polymer simulations, microscopy, and mass spectrometry to dissect the roles played by heterochromatin- and lamina-mediated interactions in nuclear organization. Our model explains the conventional organization of heterochromatin and euchromatin in growing cells and the pathological organization found in oncogene-induced senescence and progeria. We show that the experimentally observed changes in the locality of contacts in senescent and progeroid cells can be explained as arising due to phase transitions in the system. Within our simulations, LADs are highly stochastic, as in experiments. Our model suggests that, once established, the senescent phenotype should be metastable even if lamina-mediated interactions were reinstated. Overall, our simulations uncover a generic physical mechanism that can regulate heterochromatin segregation and LAD formation in a wide range of mammalian nuclei.

Core mechanisms of drag enhancement on bodies settling in a stratified fluid

Stratification due to salt or heat gradients greatly affects the distribution of inert particles and living organisms in the ocean and the lower atmosphere. Laboratory studies considering the settling of a sphere in a linearly stratified fluid confirmed that stratification may dramatically enhance the drag on the body, but failed to identify the generic physical mechanism responsible for this increase. We present a rigorous splitting scheme of the various contributions to the drag on a settling body, which allows them to be properly disentangled whatever the relative magnitude of inertial, viscous, diffusive and buoyancy effects. We apply this splitting procedure to data obtained via direct numerical simulation of the flow past a settling sphere over a range of parameters covering a variety of situations of laboratory and geophysical interest. Contrary to widespread belief, we show that, in the parameter range covered by the simulations, the drag enhancement is generally not primarily due to the extra buoyancy force resulting from the dragging of light fluid by the body, but rather to the specific structure of the vorticity field set in by buoyancy effects. Simulations also reveal how the different buoyancy-induced contributions to the drag vary with the flow parameters. To unravel the origin of these variations, we analyse the different possible leading-order balances in the governing equations. Thanks to this procedure, we identify several distinct regimes which differ by the relative magnitude of length scales associated with stratification, viscosity and diffusivity. We derive the scaling laws of the buoyancy-induced drag contributions in each of these regimes. Considering tangible examples, we show how these scaling laws combined with numerical results may be used to obtain reliable predictions beyond the range of parameters covered by the simulations.

Quantum tunneling of Davydov solitons through massive barriers

Protein clamps provide the cell with effective mechanisms for sensing of environmental changes and triggering adaptations that maintain homeostasis. The general physical mechanism behind protein clamping action, however, is poorly understood. Here, we explore the Davydov model for quantum transport of amide I energy, which is self-trapped in soliton states that propagate along the protein {\alpha}-helix spines and preserve their shape upon reflection from the {\alpha}-helix ends. We study computationally whether the Davydov solitons are able to reflect from massive barriers that model the presence of external protein clamps acting on a portion of the {\alpha}-helix, and characterize the range of barrier conditions for which the Davydov solitons are capable of tunneling through the barrier. The simulations showed that the variability of amino acid masses in proteins has a negligible effect on Davydov soliton dynamics, but a massive barrier that is a hundred times the mass of a single amino acid presents an obstacle for the soliton propagation. The greater width of Davydov solitons stabilizes the soliton upon reflection from such a massive barrier and increases the probability of tunneling through it, whereas the greater isotropy of the exciton-lattice coupling suppresses the tunneling efficiency by increasing the interaction time between the Davydov soliton and the barrier, thereby prolonging the tunneling time through the barrier and enhancing the probability for reflection from the latter. The results as presented, demonstrate the feasibility of Davydov solitons reflecting from or tunneling through massive barriers, and suggest a general physical mechanism underlying the action of protein clamps through local enhancement of an effective protein {\alpha}-helix mass.

Substrate-rigidity dependent migration of an idealized twitching bacterium.

Mechanical properties of the extracellular matrix are important determinants of cellular migration in diverse processes, such as immune response, wound healing, and cancer metastasis. Moreover, recent studies indicate that even bacterial surface colonization can depend on the mechanics of the substrate. Here, we focus on physical mechanisms that can give rise to substrate-rigidity dependent migration. We study a "twitcher", a cell driven by extension-retraction cycles, to idealize bacteria and perhaps eukaryotic cells that employ a slip-stick mode of motion. The twitcher is asymmetric and always pulls itself forward at its front. Analytical calculations show that the migration speed of a twitcher depends non-linearly on substrate rigidity. For soft substrates, deformations do not lead to build-up of significant force and the migration speed is therefore determined by stochastic adhesion unbinding. For rigid substrates, forced adhesion rupture determines the migration speed. Depending on the force-sensitivity of front and rear adhesions, forced bond rupture implies an increase or a decrease of the migration speed. A requirement for the occurrence of rigidity-dependent stick-slip migration is a "sticky" substrate, with binding rates being an order of magnitude larger than unbinding rates in absence of force. Computer simulations show that small stall forces of the driving machinery lead to a reduced movement on high rigidities, regardless of force-sensitivities of bonds. The simulations also confirm the occurrence of rigidity-dependent migration speed in a generic model for slip-stick migration of cells on a sticky substrate.

Onset of orbital motion in a trailing vortex from an oscillating wing

The onset and development of orbital motion of a trailing vortex from a wing undergoing small amplitude heaving motion is investigated using stereo particle image velocimetry in conjunction with three-dimensional reconstruction techniques. The effect of Strouhal number is examined via space–time representations of axial and azimuthal vorticity, axial velocity deficit and swirl ratio. At low Strouhal number, the undulation of the vortex remains unidirectional with no amplification in the streamwise direction. In contrast, at high Strouhal number, the amplitude of vortex undulation can increase by up to a factor of ten in the streamwise direction. These large amplitudes occur during orbital motion of the vortex. Irrespective of the value of either the Strouhal number of excitation or the streamwise location along the undulating vortex, generic physical mechanisms occur. Changes in curvature along the vortex are closely related to changes in the axial velocity deficit, extreme values of axial vorticity and swirl ratio and the onset and attenuation of pronounced azimuthal vorticity.

A fluid-to-solid jamming transition underlies vertebrate body axis elongation.

Just as in clay molding or glass blowing, sculpting biological structures requires the constituent material to locally flow like a fluid while maintaining overall mechanical integrity like a solid. Disordered soft materials, such as foams, emulsions and colloidal suspensions, switch from fluid-like to solid-like behaviors at a jamming transition1–4. Similarly, cell collectives have been shown to display glassy dynamics in 2D and 3D5,6 and jamming in cultured epithelial monolayers7,8, behaviors recently predicted theoretically9–11 and proposed to influence asthma pathobiology8 and tumor progression12. However, it is unknown if these seemingly universal behaviors occur in vivo and, specifically, if they play any functional role during embryonic morphogenesis. By combining direct in vivo measurements of tissue mechanics with analysis of cellular dynamics, we show that during vertebrate body axis elongation, posterior tissues undergo a jamming transition from a fluid-like behavior at the extending end, the mesodermal progenitor zone (MPZ), to a solid-like behavior in the presomitic mesoderm (PSM). We uncover an anteroposterior, N-cadherin-dependent gradient in yield stress that provides increasing mechanical integrity to the PSM, consistent with the tissue transiting from a wetter to a dryer foam-like architecture. Our results show that cell-scale stresses fluctuate rapidly (~1 min), enabling cell rearrangements and effectively ‘melting’ the tissue at the growing end. Persistent (>0.5 h) stresses at supracellular scales, rather than cell-scale stresses, guide morphogenetic flows in fluid-like tissue regions. Unidirectional axis extension is sustained by the reported PSM rigidification, which mechanically supports posterior, fluid-like tissues during remodeling prior to their maturation. The spatiotemporal control of fluid-like and solid-like tissue states may represent a generic physical mechanism of embryonic morphogenesis.

A physical mechanism of magnetoreception: Extension and analysis.

Proposed is a general physical mechanism of magnetoreception of weak magnetic fields (MFs). The mechanism is based on classical precessional dynamics of a magnetic moment in a thermally disturbed environment and includes a minimum of necessary parameters-the gyromagnetic ratio, thermal relaxation time, and rate of downstream events generated by changes in the state of the magnetic moment. The mechanism imposes general restrictions on the probability of initial biophysical magnetic transduction event before the involvement of specific biophysical and biochemical mechanisms-i.e., regardless of the nature of an MF target and the subsequent cascade of events. It is shown that biological effects of weak MFs have, in certain cases, nonlinear and frequency selective properties. The observation of these characteristics provides information not only on the target's gyromagnetic ratio, but also on the parameters of its interaction with the immediate environment. This enables one to develop experimental strategies for identifying the biophysical mechanisms of magnetoreception including the specific case of effects of a near-zero MF exposure. The mechanism is universally applicable to magnetic moments of different nature, in particular, of electron and proton orbital motion and of spins. Experimental exposure conditions are derived which would lead to validation of the proposed mechanism. Bioelectromagnetics. 38:41-52, 2017. © 2016 Wiley Periodicals, Inc.

Modeling magnetosensitive ion channels in the viscoelastic environment of living cells.

We propose and study a model of hypothetical magnetosensitive ionic channels which are long thought to be a possible candidate to explain the influence of weak magnetic fields on living organisms ranging from magnetotactic bacteria to fishes, birds, rats, bats, and other mammals including humans. The core of the model is provided by a short chain of magnetosomes serving as a sensor, which is coupled by elastic linkers to the gating elements of ion channels forming a small cluster in the cell membrane. The magnetic sensor is fixed by one end on cytoskeleton elements attached to the membrane and is exposed to viscoelastic cytosol. Its free end can reorient stochastically and subdiffusively in viscoelastic cytosol responding to external magnetic field changes and can open the gates of coupled ion channels. The sensor dynamics is generally bistable due to bistability of the gates which can be in two states with probabilities which depend on the sensor orientation. For realistic parameters, it is shown that this model channel can operate in the magnetic field of Earth for a small number (five to seven) of single-domain magnetosomes constituting the sensor rod, each of which has a typical size found in magnetotactic bacteria and other organisms or even just one sufficiently large nanoparticle of a characteristic size also found in nature. It is shown that, due to the viscoelasticity of the medium, the bistable gating dynamics generally exhibits power law and stretched exponential distributions of the residence times of the channels in their open and closed states. This provides a generic physical mechanism for the explanation of the origin of such anomalous kinetics for other ionic channels whose sensors move in a viscoelastic environment provided by either cytosol or biological membrane, in a quite general context, beyond the fascinating hypothesis of magnetosensitive ionic channels we explore.

Long-Range Correlated Dynamics in Intrinsically Disordered Proteins

Intrinsically disordered proteins (IDPs) are involved in a wide variety of physiological and pathological processes and are best described by ensembles of rapidly interconverting conformers. Using fast field cycling relaxation measurements we here show that the IDP α-synuclein as well as a variety of other IDPs undergoes slow reorientations at time scales comparable to folded proteins. The slow motions are not perturbed by mutations in α-synuclein, which are related to genetic forms of Parkinson's disease, and do not depend on secondary and tertiary structural propensities. Ensemble-based hydrodynamic calculations suggest that the time scale of the underlying correlated motion is largely determined by hydrodynamic coupling between locally rigid segments. Our study indicates that long-range correlated dynamics are an intrinsic property of IDPs and offers a general physical mechanism of correlated motions in highly flexible biomolecular systems.

Hydrodynamic instabilities provide a generic route to spontaneous biomimetic oscillations in chemomechanically active filaments

Non-equilibrium processes which convert chemical energy into mechanical motion enable the motility of organisms. Bundles of inextensible filaments driven by energy transduction of molecular motors form essential components of micron-scale motility engines like cilia and flagella. The mimicry of cilia-like motion in recent experiments on synthetic active filaments supports the idea that generic physical mechanisms may be sufficient to generate such motion. Here we show, theoretically, that the competition between the destabilising effect of hydrodynamic interactions induced by force-free and torque-free chemomechanically active flows, and the stabilising effect of nonlinear elasticity, provides a generic route to spontaneous oscillations in active filaments. These oscillations, reminiscent of prokaryotic and eukaryotic flagellar motion, are obtained without having to invoke structural complexity or biochemical regulation. This minimality implies that biomimetic oscillations, previously observed only in complex bundles of active filaments, can be replicated in simple chains of generic chemomechanically active beads.

Superconductor-insulator transition controlled by annealing in Ga implanted Si

Heavily Ga implanted Si nanolayers covered with a thin SiO2 layer exhibit a superconductor-insulator transition in dependence on annealing conditions. The transition characteristics resemble those of ultrathin quench-condensed metal films although the implanted layer differs clearly in composition, width, and nanostructure. This implies a general physical mechanism for the superconductor-insulator transition in thin, disordered layers which is supposed to be a quantum phase transition between dual states—the superconducting and the superinsulating one. There is a resistance criterion for the phase transition closely associated with a critical hole concentration.

Mesoderm layer formation in Xenopus and Drosophila gastrulation

During gastrulation, the mesoderm spreads out between ectoderm and endoderm to form a mesenchymal cell layer. Surprisingly the underlying principles of mesoderm layer formation are very similar in evolutionarily distant species like the fruit fly, Drosophila melanogaster, and the frog, Xenopus laevis, in which the molecular and the cellular basis of mesoderm layer formation have been extensively studied. Complementary expression of growth factors in the ectoderm and their receptors in the mesoderm act to orient cellular protrusive activities and direct cell movement, leading to radial cell intercalation and the spreading of the mesoderm layer. This mechanism is contrasted with generic physical mechanisms of tissue spreading that consider the adhesive and physical properties of the cells and tissues. Both mechanisms need to be integrated to orchestrate mesenchymal morphogenesis.