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Advances in Experimental Medicine and... 2020Diffusion within bacteria is often thought of as a "simple" random process by which molecules collide and interact with each other. New research however shows that this... (Review)
Review
Diffusion within bacteria is often thought of as a "simple" random process by which molecules collide and interact with each other. New research however shows that this is far from the truth. Here we shed light on the complexity and importance of diffusion in bacteria, illustrating the similarities and differences of diffusive behaviors of molecules within different compartments of bacterial cells. We first describe common methodologies used to probe diffusion and the associated models and analyses. We then discuss distinct diffusive behaviors of molecules within different bacterial cellular compartments, highlighting the influence of metabolism, size, crowding, charge, binding, and more. We also explicitly discuss where further research and a united understanding of what dictates diffusive behaviors across the different compartments of the cell are required, pointing out new research avenues to pursue.
Topics: Bacteria; Biophysical Phenomena; Diffusion
PubMed: 32894475
DOI: 10.1007/978-3-030-46886-6_2 -
Progress in Nuclear Magnetic Resonance... 2021Relaxation and diffusion NMR measurements offer an approach to studying rotational and translational motion of molecules non-invasively, and they also provide chemical... (Review)
Review
Relaxation and diffusion NMR measurements offer an approach to studying rotational and translational motion of molecules non-invasively, and they also provide chemical resolution complementary to NMR spectra. Multidimensional experiments enable the correlation of relaxation and diffusion parameters as well as the observation of molecular exchange phenomena through relaxation or diffusion contrast. This review describes how to accelerate multidimensional relaxation and diffusion measurements significantly through spatial encoding. This so-called ultrafast Laplace NMR approach shortens the experiment time to a fraction and makes even single-scan experiments possible. Single-scan experiments, in turn, significantly facilitate the use of nuclear spin hyperpolarization methods to boost sensitivity. The ultrafast Laplace NMR method is also applicable with low-field, mobile NMR instruments, and it can be exploited in many disciplines. For example, it has been used in studies of the dynamics of fluids in porous materials, identification of intra- and extracellular metabolites in cancer cells, and elucidation of aggregation phenomena in atmospheric surfactant solutions.
Topics: Diffusion; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Porosity
PubMed: 34852922
DOI: 10.1016/j.pnmrs.2021.07.001 -
Skin Pharmacology and Physiology 2022The process by which drugs leave the bloodstream to enter the skin compartments is important in determining appropriate routes of delivery and developing more... (Review)
Review
BACKGROUND
The process by which drugs leave the bloodstream to enter the skin compartments is important in determining appropriate routes of delivery and developing more efficacious medications. We conducted a general literature review on percutaneous egression mechanisms.
SUMMARY
Studies demonstrate that the stratum corneum (SC) is a compartment for systemically delivered drugs. Upon reviewing the available literature, it became apparent that there may be multiple mechanisms of percutaneous egression dependent upon drug physiochemical properties. These mechanisms include, but are not limited to, desquamation, sebum secretion, sweat transport, and passive diffusion. While drugs often utilize one major pathway, it is possible that all mechanisms may play a role to varying extents.
KEY MESSAGES
Available literature suggests that hydrophilic substances tended to travel from blood to the upper layers of the skin via sweat, whereas lipophilic substances utilized sebum secretion to reach the SC. Upon reaching the skin surface, the drugs spread laterally before penetrating back into the skin as if they were topically administered. More data are warranted to identify additional percutaneous egression mechanisms, precise drug action sites, and accelerate drug development.
Topics: Diffusion; Epidermis
PubMed: 35325893
DOI: 10.1159/000523795 -
Annual Review of Biophysics May 2022Embryonic development hinges on effective coordination of molecular events across space and time. Waves have recently emerged as constituting an ubiquitous mechanism... (Review)
Review
Embryonic development hinges on effective coordination of molecular events across space and time. Waves have recently emerged as constituting an ubiquitous mechanism that ensures rapid spreading of regulatory signals across embryos, as well as reliable control of their patterning, namely, for the emergence of body plan structures. In this article, we review a selection of recent quantitative work on signaling waves and present an overview of the theory of waves. Our aim is to provide a succinct yet comprehensive guiding reference for the theoretical frameworks by which signaling waves can arise in embryos. We start, then, from reaction-diffusion systems, both static and time dependent; move to excitable dynamics; and conclude with systems of coupled oscillators. We link these theoretical models to molecular mechanisms recently elucidated for the control of mitotic waves in early embryos, patterning of the vertebrate body axis, micropattern cultures, and bone regeneration. Our goal is to inspire experimental work that will advance theory in development and connect its predictions to quantitative biological observations.
Topics: Body Patterning; Diffusion; Embryonic Development; Signal Transduction
PubMed: 35119944
DOI: 10.1146/annurev-biophys-111521-102500 -
Current Opinion in Structural Biology Dec 2021High-resolution technologies have clarified some of the principles underlying cellular actions. However, understanding how cells receive, communicate, and respond to... (Review)
Review
High-resolution technologies have clarified some of the principles underlying cellular actions. However, understanding how cells receive, communicate, and respond to signals is still challenging. Questions include how efficient regulation of assemblies, which execute cell actions at the nanoscales, transmits productively at micrometer scales, especially considering the crowded environment, and how the cell organization makes it happen. Here, we describe how cells can navigate long-range diffusion-controlled signaling via association/dissociation of spatially proximal entities. Dynamic clusters can span the cell, engaging in most signaling steps. Effective local concentration, allostery, scaffolding, affinities, and the chemical and mechanical properties of the macromolecules and the environment play key roles. Signaling strength and duration matter, for example, deciding if a mutation promotes cancer or developmental syndromes.
Topics: Diffusion; Signal Transduction
PubMed: 34218161
DOI: 10.1016/j.sbi.2021.05.009 -
Biophysical Journal Apr 2022Biochemical specificity is critical in enzyme function, evolution, and engineering. Here we employ an established kinetic model to dissect the effects of reactant...
Biochemical specificity is critical in enzyme function, evolution, and engineering. Here we employ an established kinetic model to dissect the effects of reactant geometry and diffusion on product formation speed and accuracy in the presence of cognate (correct) and near-cognate (incorrect) substrates. Using this steady-state model for spherical geometries, we find that, for distinct kinetic regimes, the speed and accuracy of the reactions are optimized on different regions of the geometric landscape. From this model we deduce that accuracy can be strongly dependent on reactant geometric properties even for chemically limited reactions. Notably, substrates with a specific geometry and reactivity can be discriminated by the enzyme with higher efficacy than others through purely diffusive effects. For similar cognate and near-cognate substrate geometries (as is the case for polymerases or the ribosome), we observe that speed and accuracy are maximized in opposing regions of the geometric landscape. We also show that, in relevant environments, diffusive effects on accuracy can be substantial even far from extreme kinetic conditions. Finally, we find how reactant chemical discrimination and diffusion can be related to simultaneously optimize steady-state flux and accuracy. These results highlight how diffusion and geometry can be employed to enhance reaction speed and discrimination, and similarly how they impose fundamental restraints on these quantities.
Topics: Diffusion; Kinetics; Ribosomes
PubMed: 35278424
DOI: 10.1016/j.bpj.2022.03.005 -
Biophysical Journal Oct 2021Biophysical modeling of development started with Alan Turing. His two-morphogen reaction-diffusion model was a radical but powerful simplification. Despite its apparent... (Review)
Review
Biophysical modeling of development started with Alan Turing. His two-morphogen reaction-diffusion model was a radical but powerful simplification. Despite its apparent limitations, the model captured real developmental processes that only recently have been validated at the molecular level in many systems. The precision and robustness of reaction-diffusion patterning, despite boundary condition-dependence, remain active areas of investigation in developmental biology.
Topics: Computational Biology; Diffusion; Models, Biological
PubMed: 34480925
DOI: 10.1016/j.bpj.2021.08.041 -
The Journal of Physical Chemistry. B Nov 2022Living systems are characterized by their spatially highly inhomogeneous nature which is susceptible to modify fundamentally the behavior of biomolecular species,...
Living systems are characterized by their spatially highly inhomogeneous nature which is susceptible to modify fundamentally the behavior of biomolecular species, including the proteins that underpin biological functionality in cells. Spatial gradients in chemical potential are known to lead to strong transport effects for colloidal particles, but their effect on molecular scale species such as proteins has remained largely unexplored. Here, we improve on existing diffusiophoresis microfluidic technique to measure protein diffusiophoresis in real space. The measurement of proteins is made possible by two ameliorations. First, a label-free microscope is used to suppress label interference. Second, improvements in numerical methods are developed to meet the particular challenges posed by small molecules. We demonstrate that individual proteins can undergo strong diffusiophoretic motion in salt gradients in a manner which is sufficient to overcome diffusion and which leads to dramatic changes in their spatial organization on the scale of a cell. Moreover, we demonstrate that this phenomenon can be used to control the motion of proteins in microfluidic devices. These results open up a path towards a physical understanding of the role of gradients in living systems in the spatial organization of macromolecules and highlight novel routes towards protein sorting applications on device.
Topics: Diffusion; Motion; Macromolecular Substances; Sodium Chloride
PubMed: 36306420
DOI: 10.1021/acs.jpcb.2c04029 -
Journal of Neuroscience Methods Oct 2020The biophysical modeling efforts in diffusion MRI have grown considerably over the past 25 years. In this review, we dwell on the various challenges along the journey of... (Review)
Review
The biophysical modeling efforts in diffusion MRI have grown considerably over the past 25 years. In this review, we dwell on the various challenges along the journey of bringing a biophysical model from initial design to clinical implementation, identifying both hurdles that have been already overcome and outstanding issues. First, we describe the critical initial task of selecting which features of tissue microstructure can be estimated using a model and which acquisition protocol needs to be implemented to make the estimation possible. The model performance should necessarily be tested in realistic numerical simulations and in experimental data - adapting the fitting strategy accordingly, and parameter estimates should be validated against complementary techniques, when/if available. Secondly, the model performance and validity should be explored in pathological conditions, and, if appropriate, dedicated models for pathology should be developed. We build on examples from tumors, ischemia and demyelinating diseases. We then discuss the challenges associated with clinical translation and added value. Finally, we single out four major unresolved challenges that are related to: the availability of a microstructural ground truth, the validation of model parameters which cannot be accessed with complementary techniques, the development of a generalized standard model for any brain region and pathology, and the seamless communication between different parties involved in the development and application of biophysical models of diffusion.
Topics: Biophysics; Brain; Diffusion; Diffusion Magnetic Resonance Imaging
PubMed: 32692999
DOI: 10.1016/j.jneumeth.2020.108861 -
Current Opinion in Structural Biology Oct 2021Microfluidic systems under laminar flow conditions provide in-solution information about species size and binding affinities at very modest sample costs. Flow-induced... (Review)
Review
Microfluidic systems under laminar flow conditions provide in-solution information about species size and binding affinities at very modest sample costs. Flow-induced dispersion analysis directly measures the spread of the analyte profile using Taylor dispersion analysis, whereas microfluidic diffusional sizing quantifies the transfer of analyte from one phase to another. Species of sizes between 0.5 and 1000 nm can be analyzed, and different populations resolved. Both techniques also allow analysis in complex media and medium throughput analysis. These properties make them valuable complements to existing approaches to measure biomolecular interactions.
Topics: Diffusion; Microfluidics
PubMed: 33831785
DOI: 10.1016/j.sbi.2021.02.006