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Angewandte Chemie (International Ed. in... Mar 2022Numerous key biological processes rely on the concept of multivalency, where ligands achieve stable binding only upon engaging multiple receptors. These processes, like... (Review)
Review
Numerous key biological processes rely on the concept of multivalency, where ligands achieve stable binding only upon engaging multiple receptors. These processes, like viral entry or immune synapse formation, occur on the diffusive cellular membrane. One crucial, yet underexplored aspect of multivalent binding is the mobility of coupled receptors. Here, we discuss the consequences of mobility in multivalent processes from four perspectives: (I) The facilitation of receptor recruitment by the multivalent ligand due to their diffusivity prior to binding. (II) The effects of receptor preassembly, which allows their local accumulation. (III) The consequences of changes in mobility upon the formation of receptor/ligand complex. (IV) The changes in the diffusivity of lipid environment surrounding engaged receptors. We demonstrate how understanding mobility is essential for fully unravelling the principles of multivalent membrane processes, leading to further development in studies on receptor interactions, and guide the design of new generations of multivalent ligands.
Topics: Cell Membrane; Diffusion; Ligands; Lipids
PubMed: 34982497
DOI: 10.1002/anie.202114167 -
Chemphyschem : a European Journal of... Jan 2009Diffusive transport of particles or, more generally, small objects, is a ubiquitous feature of physical and chemical reaction systems. In configurations containing... (Review)
Review
Diffusive transport of particles or, more generally, small objects, is a ubiquitous feature of physical and chemical reaction systems. In configurations containing confining walls or constrictions, transport is controlled both by the fluctuation statistics of the jittering objects and the phase space available to their dynamics. Consequently, the study of transport at the macro- and nanoscales must address both Brownian motion and entropic effects. Herein we report on recent advances in the theoretical and numerical investigation of stochastic transport occurring either in microsized geometries of varying cross sections or in narrow channels wherein the diffusing particles are hindered from passing each other (single-file diffusion). For particles undergoing biased diffusion in static suspension media enclosed by confining geometries, transport exhibits intriguing features such as 1) a decrease in nonlinear mobility with increasing temperature or also 2) a broad excess peak of the effective diffusion above the free diffusion limit. These paradoxical aspects can be understood in terms of entropic contributions resulting from the restricted dynamics in phase space. If, in addition, the suspension medium is subjected to external, time-dependent forcing, rectification or segregation of the diffusing Brownian particles becomes possible. Likewise, the diffusion in very narrow, spatially modulated channels is modified via contact particle-particle interactions, which induce anomalous sub-diffusion. The effective sub-diffusion constant for a driven single file also develops a resonance-like structure as a function of the confining coupling constant.
Topics: Algorithms; Diffusion; Ion Channels; Ion Transport; Models, Theoretical; Molecular Conformation
PubMed: 19025741
DOI: 10.1002/cphc.200800526 -
Science (New York, N.Y.) Feb 1964Fluorescein-sodium, a fluorescent tracer whose molecular weight is 376, diffuses rather freely from the interior of one cell to another in a gland epithelium...
Fluorescein-sodium, a fluorescent tracer whose molecular weight is 376, diffuses rather freely from the interior of one cell to another in a gland epithelium (Drosophila) but does not diffuse along the intercellular space to the exterior. The permeability of the junctional surfaces of the cell membranes appears to be high, in contrast to the nonjunctional surfaces and intercellular spaces which represent strong diffusion barriers.
Topics: Animals; Cell Biology; Cell Membrane; Diffusion; Drosophila; Epithelium; Fluoresceins; Research; Salivary Glands
PubMed: 14090146
DOI: 10.1126/science.143.3609.959 -
Journal of Biological Physics Sep 2023We present an analysis of an epidemic spreading process on an Apollonian network that can describe an epidemic spreading in a non-sedentary population. We studied the...
We present an analysis of an epidemic spreading process on an Apollonian network that can describe an epidemic spreading in a non-sedentary population. We studied the modified diffusive epidemic process using the Monte Carlo method by computational analysis. Our model may be helpful for modeling systems closer to reality consisting of two classes of individuals: susceptible (A) and infected (B). The individuals can diffuse in a network according to constant diffusion rates [Formula: see text] and [Formula: see text], for the classes A and B, respectively, and obeying three diffusive regimes, i.e., [Formula: see text], [Formula: see text], and [Formula: see text]. Into the same site i, the reaction occurs according to the dynamical rule based on Gillespie's algorithm. Finite-size scaling analysis has shown that our model exhibits continuous phase transition to an absorbing state with a set of critical exponents given by [Formula: see text], [Formula: see text], and [Formula: see text] familiar to every investigated regime. In summary, the continuous phase transition, characterized by this set of critical exponents, does not have the same exponents of the mean-field universality class in both regular lattices and complex networks.
Topics: Humans; Computer Simulation; Algorithms; Epidemics; Models, Biological; Diffusion
PubMed: 37118345
DOI: 10.1007/s10867-023-09634-2 -
Physical Review Letters Nov 2022We investigate the dynamics of a single chiral active particle subject to an external torque due to the presence of a gravitational field. Our computer simulations...
We investigate the dynamics of a single chiral active particle subject to an external torque due to the presence of a gravitational field. Our computer simulations reveal an arbitrarily strong increase of the long-time diffusivity of the gravitactic agent when the external torque approaches the intrinsic angular drift. We provide analytic expressions for the mean-square displacement in terms of eigenfunctions and eigenvalues of the noisy-driven-pendulum problem. The pronounced maximum in the diffusivity is then rationalized by the vanishing of the lowest eigenvalues of the Fokker-Planck equation for the angular motion as the rotational diffusion decreases and the underlying classical bifurcation is approached. A simple harmonic-oscillator picture for the barrier-dominated motion provides a quantitative description for the onset of the resonance while its range of validity is determined by the crossover to a critical-fluctuation-dominated regime.
Topics: Diffusion; Computer Simulation; Motion
PubMed: 36493425
DOI: 10.1103/PhysRevLett.129.228003 -
Physical Review Letters Jun 2023Noninterferometric experiments have been successfully employed to constrain models of spontaneous wave function collapse, which predict a violation of the quantum...
Noninterferometric experiments have been successfully employed to constrain models of spontaneous wave function collapse, which predict a violation of the quantum superposition principle for large systems. These experiments are grounded on the fact that, according to these models, the dynamics is driven by noise that, besides collapsing the wave function in space, generates a diffusive motion with characteristic signatures, which, though small, can be tested. The noninterferometric approach might seem applicable only to those models that implement the collapse through noisy dynamics, not to any model, that collapses the wave function in space. Here, we show that this is not the case: under reasonable assumptions, any collapse dynamics (in space) is diffusive. Specifically, we prove that any space-translation covariant dynamics that complies with the no-signaling constraint, if collapsing the wave function in space, must change the average momentum of the system and/or its spread.
Topics: Motion; Diffusion
PubMed: 37354406
DOI: 10.1103/PhysRevLett.130.230202 -
ACS Nano Nov 2020Collective decision making by living cells is facilitated by exchange of diffusible signals where sender cells release a chemical signal that is interpreted by receiver...
Collective decision making by living cells is facilitated by exchange of diffusible signals where sender cells release a chemical signal that is interpreted by receiver cells. A variety of nonliving artificial cell models have been developed in recent years that mimic various aspects of diffusion-based intercellular communication. However, localized secretion of diffusive signals from individual protocells, which is critical for mimicking biological sender-receiver systems, has remained challenging to control precisely. Here, we engineer light-responsive, DNA-encoded sender-receiver architectures, where protein-polymer microcapsules act as cell mimics and molecular communication occurs through diffusive DNA signals. We prepare spatial distributions of sender and receiver protocells using a microfluidic trapping array and set up a signaling gradient from a single sender cell using light, which activates surrounding receivers through DNA strand displacement. Our systematic analysis reveals how the effective signal range of a single sender is determined by various factors including the density and permeability of receivers, extracellular signal degradation, signal consumption, and catalytic regeneration. In addition, we construct a three-population configuration where two sender cells are embedded in a dense array of receivers that implement Boolean logic and investigate spatial integration of nonidentical input cues. The results offer a means for studying diffusion-based sender-receiver topologies and present a strategy to achieve the congruence of reaction-diffusion and positional information in chemical communication systems that have the potential to reconstitute collective cellular patterns.
Topics: Artificial Cells; Cell Communication; DNA; Diffusion; Signal Transduction
PubMed: 33078948
DOI: 10.1021/acsnano.0c07537 -
Annual Review of Physical Chemistry 2001We outline recent developments in biological single-molecule fluorescence detection with particular emphasis on observations by ratiometric fluorescence resonance energy... (Review)
Review
We outline recent developments in biological single-molecule fluorescence detection with particular emphasis on observations by ratiometric fluorescence resonance energy transfer (FRET) of biomolecules freely diffusing in solution. Single-molecule-diffusion methodologies were developed to minimize perturbations introduced by interactions between molecules and surfaces. Confocal microscopy is used in combination with sensitive detectors to observe bursts of photons from fluorescently labeled biomolecules as they diffuse through the focal volume. These bursts are analyzed to extract ratiometric observables such as FRET efficiency and polarization anisotropy. We describe the development of single-molecule FRET methodology and its application to the observation of the Förster distance dependence and the study of protein folding and polymer physics problems. Finally, we discuss future advances in data acquisition and analysis techniques that can provide a more complete picture of the accessible molecular information.
Topics: Biopolymers; Diffusion; Energy Transfer; Fluorescence; Protein Folding; Proteins; Radiometry
PubMed: 11326065
DOI: 10.1146/annurev.physchem.52.1.233 -
Biophysical Journal May 2019Rebinding kinetics of molecular ligands plays a key role in the operation of biomachinery, from regulatory networks to protein transcription, and is also a key factor in...
Rebinding kinetics of molecular ligands plays a key role in the operation of biomachinery, from regulatory networks to protein transcription, and is also a key factor in design of 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 that occurs in vivo, e.g., during exocytosis. Via scaling arguments and molecular dynamic simulations, we analyze the dependence of nonequilibrium rebinding kinetics on two intrinsic length scales: the average separation distance between the binding sites and the total diffusible volume (i.e., 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 diffusion-limited binding, the (rebinding) on rate decreases with time via multiple power-law regimes before the terminal steady-state (constant on-rate) regime. At intermediate times, when particle density has not yet become uniform throughout the diffusible volume, the cumulative number of rebindings exhibits a novel, to our knowledge, plateau behavior because of the three-dimensional escape process of ligands from binding sites. The duration of the plateau regime depends on the average separation distance between binding sites. After 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 (e.g., longer residence times) delay entry to the power-law regimes. Our results will be useful for extracting hidden timescales in experiments such as kinetic rate measurements for ligand-receptor interactions in microchannels, as well as for cell signaling via diffusing molecules.
Topics: Binding Sites; Diffusion; Kinetics; Ligands; Molecular Dynamics Simulation; Protein Binding; Protein Conformation; Proteins
PubMed: 31029377
DOI: 10.1016/j.bpj.2019.02.033 -
Biomaterials Oct 2023Flourished in the past two decades, fluorescent probe technology provides researchers with accurate and efficient tools for in situ imaging of biomarkers in living cells... (Review)
Review
Flourished in the past two decades, fluorescent probe technology provides researchers with accurate and efficient tools for in situ imaging of biomarkers in living cells and tissues and may play a significant role in clinical diagnosis and treatment such as biomarker detection, fluorescence imaging-guided surgery, and photothermal/photodynamic therapy. In situ imaging of biomarkers depends on the spatial resolution of molecular probes. Nevertheless, the majority of currently available molecular fluorescent probes suffer from the drawback of diffusing from the target region. This leads to a rapid attenuation of the fluorescent signal over time and a reduction in spatial resolution. Consequently, the diffused fluorescent signal cannot accurately reflect the in situ information of the target. Self-immobilizing and self-precipitating molecular fluorescent probes can be used to overcome this problem. These probes ensure that the fluorescent signal remains at the location where the signal is generated for a long time. In this review, we introduce the development history of the two types of probes and classify them in detail according to different design strategies. In addition, we compare their advantages and disadvantages, summarize some representative studies conducted in recent years, and propose prospects for this field.
Topics: Fluorescent Dyes; Molecular Probes; Diagnostic Imaging; Diffusion; Photothermal Therapy
PubMed: 37643487
DOI: 10.1016/j.biomaterials.2023.122281