-
Science Advances Sep 2022Designed and engineered protein and DNA nanopores can be used to sense and characterize single molecules and control transmembrane transport of molecular species....
Designed and engineered protein and DNA nanopores can be used to sense and characterize single molecules and control transmembrane transport of molecular species. However, designed biomolecular pores are less than 100 nm in length and are used primarily for transport across lipid membranes. Nanochannels that span longer distances could be used as conduits for molecules between nonadjacent compartments or cells. Here, we design micrometer-long, 7-nm-diameter DNA nanochannels that small molecules can traverse according to the laws of continuum diffusion. Binding DNA origami caps to channel ends eliminates transport and demonstrates that molecules diffuse from one channel end to the other rather than permeating through channel walls. These micrometer-length nanochannels can also grow, form interconnects, and interface with living cells. This work thus shows how to construct multifunctional, dynamic agents that control molecular transport, opening ways of studying intercellular signaling and modulating molecular transport between synthetic and living cells.
Topics: Biological Transport; DNA; Diffusion; Nanopores; Nanotechnology
PubMed: 36070388
DOI: 10.1126/sciadv.abq4834 -
Advances in Experimental Medicine and... 2020Oxygen delivery to tissue mitochondria relies on simple diffusion in the target cells and tissues. As such, intracellular availability of O in tissue depends on its... (Review)
Review
Oxygen delivery to tissue mitochondria relies on simple diffusion in the target cells and tissues. As such, intracellular availability of O in tissue depends on its solubility and diffusivity in complex and heterogeneous macromolecular environments. The path of oxygen diffusion is key to its rate of transfer, especially where pathways of differing favorability are present. Most commonly, aqueous media, such as interstitial fluid and cytoplasm, are assumed to provide the dominant diffusion path. Here, the 'hydrophobic channeling' hypothesis is revisited, and several lines of evidence pointing toward lipid-accelerated oxygen diffusion pathways are discussed. The implications of hydrophobic channeling are considered in light of extended membrane networks in cells and tissues.
Topics: Cells; Diffusion; Hydrophobic and Hydrophilic Interactions; Lipid Metabolism; Lipids; Mitochondria; Oxygen
PubMed: 31893409
DOI: 10.1007/978-3-030-34461-0_23 -
Environmental Science & Technology May 2024Molecular diffusion of chemical species in subsurface environments─rock formations, soil sediments, marine, river, and lake sediments─plays a critical role in a...
Molecular diffusion of chemical species in subsurface environments─rock formations, soil sediments, marine, river, and lake sediments─plays a critical role in a variety of dynamic processes, many of which affect water chemistry. We investigate and demonstrate the occurrence of anomalous (non-Fickian) diffusion behavior, distinct from classically assumed Fickian diffusion. We measured molecular diffusion through a series of five chalk and dolomite rock samples over a period of about two months. We demonstrate that in all cases, diffusion behavior is significantly different than Fickian. We then analyze the results using a continuous time random walk framework that can describe anomalous diffusion in heterogeneous porous materials such as rock. This methodology shows extreme long-time tailing of tracer advance as compared to conventional Fickian diffusion processes. The finding that distinct anomalous diffusion occurs ubiquitously implies that diffusion-driven processes in subsurface zones should be analyzed using tools that account for non-Fickian diffusion.
Topics: Diffusion; Porosity; Geologic Sediments
PubMed: 38736287
DOI: 10.1021/acs.est.4c01386 -
The Journal of Cell Biology May 2023Single-particle tracking microscopy is a powerful technique to investigate how proteins dynamically interact with their environment in live cells. However, the analysis...
Single-particle tracking microscopy is a powerful technique to investigate how proteins dynamically interact with their environment in live cells. However, the analysis of tracks is confounded by noisy molecule localization, short tracks, and rapid transitions between different motion states, notably between immobile and diffusive states. Here, we propose a probabilistic method termed ExTrack that uses the full spatio-temporal information of tracks to extract global model parameters, to calculate state probabilities at every time point, to reveal distributions of state durations, and to refine the positions of bound molecules. ExTrack works for a wide range of diffusion coefficients and transition rates, even if experimental data deviate from model assumptions. We demonstrate its capacity by applying it to slowly diffusing and rapidly transitioning bacterial envelope proteins. ExTrack greatly increases the regime of computationally analyzable noisy single-particle tracks. The ExTrack package is available in ImageJ and Python.
Topics: Bacterial Proteins; Diffusion; Kinetics; Microscopy
PubMed: 36880553
DOI: 10.1083/jcb.202208059 -
Medical Physics May 2022The goal of this work is to provide temperature and concentration calibration of water diffusivity in polyvinylpyrrolidone (PVP) solutions used in phantoms to assess...
OBJECTIVE
The goal of this work is to provide temperature and concentration calibration of water diffusivity in polyvinylpyrrolidone (PVP) solutions used in phantoms to assess system bias and linearity in apparent diffusion coefficient (ADC) measurements.
METHOD
ADC measurements were performed for 40 kDa (K40) PVP of six concentrations (0%, 10%, 20%, 30%, 40%, and 50% by weight) at three temperatures (19.5°C, 22.5°C, and 26.4°C), with internal phantom temperature monitored by optical thermometer (±0.2°C). To achieve ADC measurement and fit accuracy of better than 0.5%, three orthogonal diffusion gradients were calibrated using known water diffusivity at 0°C and system gradient nonlinearity maps. Noise-floor fit bias was also controlled by limiting the maximum b-value used for ADC calculation of each sample. The ADC temperature dependence was modeled by Arrhenius functions of each PVP concentration. The concentration dependence was modeled by quadratic function for ADC normalized by the theoretical water diffusion values. Calibration coefficients were obtained from linear regression model fits.
RESULTS
Measured phantom ADC values increased with temperature and decreasing PVP concentration, [PVP]. The derived Arrhenius model parameters for [PVP] between 0% and 50%, are reported and can be used for K40 ADC temperature calibration with absolute ADC error within ±0.016 μm /ms. Arrhenius model fit parameters normalized to water value scaled with [PVP] between 10% and 40%, and proportional change in activation energy increased faster than collision frequency. ADC normalization by water diffusivity, D , from the Speedy-Angell relation accounted for the bulk of temperature dependence (±0.035 μm /ms) and yielded quadratic calibration for ADC /D = (12.5 ± 0.7) ·10 ·[PVP] - (23.2 ± 0.3)·10 ·[PVP]+1, nearly independent of PVP molecular weight and temperature.
CONCLUSION
The study provides ground-truth ADC values for K40 PVP solutions commonly used in diffusion phantoms for scanning at ambient room temperature. The described procedures and the reported calibration can be used for quality control and standardization of measured ADC values of PVP at different concentrations and temperatures.
Topics: Diffusion; Diffusion Magnetic Resonance Imaging; Phantoms, Imaging; Povidone; Temperature; Water
PubMed: 35184316
DOI: 10.1002/mp.15556 -
Nature Communications Feb 2018Reptation theory has been highly successful in explaining the unusual material properties of entangled polymer solutions. It reduces the complex many-body dynamics to a...
Reptation theory has been highly successful in explaining the unusual material properties of entangled polymer solutions. It reduces the complex many-body dynamics to a single-polymer description, where each polymer is envisaged to be confined to a tube through which it moves in a snake-like fashion. For flexible polymers, reptation theory has been amply confirmed by both experiments and simulations. In contrast, for semiflexible polymers, experimental and numerical tests are either limited to the onset of reptation, or were performed for tracer polymers in a fixed, static matrix. Here, we report Brownian dynamics simulations of entangled solutions of semiflexible polymers, which show that curvilinear motion along a tube (reptation) is no longer the dominant mode of dynamics. Instead, we find that polymers disentangle due to correlated constraint release, which leads to equilibration of internal bending modes before polymers diffuse the full tube length. The physical mechanism underlying terminal stress relaxation is rotational diffusion mediated by disentanglement rather than curvilinear motion along a tube.
Topics: Biopolymers; Computer Simulation; Diffusion; Models, Chemical; Molecular Dynamics Simulation; Motion; Nonlinear Dynamics; Solutions
PubMed: 29402889
DOI: 10.1038/s41467-018-02837-5 -
Journal of the Royal Society, Interface Mar 2022Patterns in nature are fascinating both aesthetically and scientifically. Alan Turing's celebrated reaction-diffusion model of pattern formation from the 1950s has been...
Patterns in nature are fascinating both aesthetically and scientifically. Alan Turing's celebrated reaction-diffusion model of pattern formation from the 1950s has been extended to an astounding diversity of applications: from cancer medicine, via nanoparticle fabrication, to computer architecture. Recently, several authors have studied pattern formation in underlying networks, but thus far, controlling a reaction-diffusion system in a network to obtain a particular pattern has remained elusive. We present a solution to this problem in the form of an analytical framework and numerical algorithm for optimal control of Turing patterns in networks. We demonstrate our method's effectiveness and discuss factors that affect its performance. We also pave the way for multidisciplinary applications of our framework beyond reaction-diffusion models.
Topics: Algorithms; Diffusion; Models, Biological
PubMed: 35259961
DOI: 10.1098/rsif.2021.0739 -
Journal of Molecular Biology Oct 2018DNA mismatch repair (MMR) corrects DNA base-pairing errors that occur during DNA replication. MMR catalyzes strand-specific DNA degradation and resynthesis by dynamic... (Review)
Review
DNA mismatch repair (MMR) corrects DNA base-pairing errors that occur during DNA replication. MMR catalyzes strand-specific DNA degradation and resynthesis by dynamic molecular coordination of sequential downstream pathways. The temporal and mechanistic order of molecular events is essential to insure interactions in MMR that occur over long distances on the DNA. Biophysical real-time studies of highly conserved components on mismatched DNA have shed light on the mechanics of MMR. Single-molecule imaging has visualized stochastically coordinated MMR interactions that are based on thermal fluctuation-driven motions. In this review, we describe the role of diffusivity and stochasticity in MMR beginning with mismatch recognition through strand-specific excision. We conclude with a perspective of the possible research directions that should solve the remaining questions in MMR.
Topics: Animals; Biophysical Phenomena; DNA; DNA Mismatch Repair; Diffusion; Humans; Multiprotein Complexes; Stochastic Processes; Thermodynamics
PubMed: 29792877
DOI: 10.1016/j.jmb.2018.05.032 -
Proceedings of the National Academy of... Sep 2022Understanding the physical principle that governs the stimuli-induced swelling and shrinking kinetics of hydrogels is indispensable for their applications. Here, we show...
Understanding the physical principle that governs the stimuli-induced swelling and shrinking kinetics of hydrogels is indispensable for their applications. Here, we show that the shrinking and swelling kinetics of self-healing hydrogels could be intrinsically asymmetric. The structure frustration, formed by the large difference in the heat and solvent diffusions, remarkably slows down the shrinking kinetics. The plateau modulus of viscoelastic gels is found to be a key parameter governing the formation of structure frustration and, in turn, the asymmetric swelling and shrinking kinetics. This work provides fundamental understandings on the temperature-triggered transient structure formation in self-healing hydrogels. Our findings will find broad use in diverse applications of self-healing hydrogels, where cooperative diffusion of water and gel network is involved. Our findings should also give insight into the molecular diffusion in biological systems that possess macromolecular crowding environments similar to self-healing hydrogels.
Topics: Diffusion; Hydrogels; Kinetics; Temperature; Water
PubMed: 36037384
DOI: 10.1073/pnas.2207422119 -
Journal of Bacteriology Sep 2019OmpA-like proteins are involved in the stabilization of the outer membrane, resistance to osmotic stress, and pathogenesis. In , OmpA2 forms a physiologically relevant...
OmpA-like proteins are involved in the stabilization of the outer membrane, resistance to osmotic stress, and pathogenesis. In , OmpA2 forms a physiologically relevant concentration gradient that forms by an uncharacterized mechanism, in which the gradient orientation depends on the position of the gene locus. This suggests that OmpA2 is synthesized and translocated to the periplasm close to the position of the gene and that the gradient forms by diffusion of the protein from this point. To further understand how the OmpA2 gradient is established, we determined the localization and mobility of the full protein and of its two structural domains. We show that OmpA2 does not diffuse and that both domains are required for gradient formation. The C-terminal domain binds tightly to the cell wall and the immobility of the full protein depends on the binding of this domain to the peptidoglycan; in contrast, the N-terminal membrane β-barrel diffuses slowly. Our results support a model in which once OmpA2 is translocated to the periplasm, the N-terminal membrane β-barrel is required for an initial fast restriction of diffusion until the position of the protein is stabilized by the binding of the C-terminal domain to the cell wall. The implications of these results on outer membrane protein diffusion and organization are discussed. Protein concentration gradients play a relevant role in the organization of the bacterial cell. The protein OmpA2 forms an outer membrane polar concentration gradient. To understand the molecular mechanism that determines the formation of this gradient, we characterized the mobility and localization of the full protein and of its two structural domains an integral outer membrane β-barrel and a periplasmic peptidoglycan binding domain. Each domain has a different role in the formation of the OmpA2 gradient, which occurs in two steps. We also show that the OmpA2 outer membrane β-barrel can diffuse, which is in contrast to what has been reported previously for several integral outer membrane proteins in , suggesting a different organization of the outer membrane proteins.
Topics: Bacterial Outer Membrane; Bacterial Outer Membrane Proteins; Caulobacter crescentus; Diffusion; Gene Expression Regulation, Bacterial; Protein Folding
PubMed: 31209077
DOI: 10.1128/JB.00177-19