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Robert Eisenberg

Publications and source records attributed to Robert Eisenberg.

14 recordsLinked to original sources

AQP4 Regulates Gap-Dominated Glymphatic Clearance through Dynamic Gliovascular Coupling

Aquaporin-4 (AQP4) is enriched at perivascular astrocytic endfeet, and impaired AQP4 function or localization is associated with reduced glymphatic transport. However, mechanical models suggest that pressure-driven exchange across the gliovascular interface occurs predominantly through inter-endfoot gaps rather than directly through the AQP4-rich membrane. How AQP4 regulates clearance in such a gap-dominated system remains unclear. We develop a reduced arterial PVS-ECS-venous PVS model coupling vascular deformation, AQP4-mediated endfoot water exchange, dynamic inter-endfoot gap regulation, and tracer transport. Cardiac-like oscillations generate strong bidirectional exchange but weak net clearance, whereas asymmetric vasodilation enhances directional transport by suppressing recovery-phase backflow. Dynamic gap regulation provides additional hydraulic rectification. Although gap-mediated flux is much larger than direct AQP4-mediated flux, PVS-facing AQP4 substantially affects clearance by altering the pressure--volume balance and hence the driving force for the dominant gap pathway. Reducing PVS-facing AQP4 permeability, or redistributing AQP4 away from the PVS-facing membrane at fixed total conductance, reduces cumulative venous output by about 40\%. Aging-like changes in vascular motion, PVS mechanical coupling, and perivascular AQP4 enrichment further compound this impairment. These results suggest that AQP4 regulates gap-dominated glymphatic clearance through dynamic hydraulic coupling at the gliovascular interface.

physics.med-ph↗

A novel multiscale modelling for the hemodynamics in retinal microcirculation with an analytic solution for the capillary-tissue coupled system

Mathematical modelling of the microcirculatory hemodynamics in the retina is an essential tool for understanding various diseases of the retina, yet remains challenging due to the multiscale nature of the retinal vasculature and its coupling to surrounding tissue. To address this, we develop a multiscale model that couples retinal vasculature across scales with interstitial tissue. Our model combines the one-dimensional (1D) model for arterioles and venules with the coupled Darcy equations for capillaries and tissue. The model uses an analytic solution for capillary-tissue coupled system that provides a simple interpretation of the results along with much faster computation. The analytic solution implies a dynamic coupling condition that links the capillary bed with upstream arteriolar and downstream venular flows. The model is mathematically robust, demonstrated through analysis of the solution's truncation error and convergence. Its predictive accuracy is validated against experimental data and other models, making it useful in interpreting experimental results. Finally, the role of various parameters in controlling retinal hemodynamics is explored.

physics.bio-ph↗

Kirchhoff`s Forgotten Contributions to Electromagnetism: Continuity Equation versus Displacement Currents

In 1857, Kirchhoff published two seminal papers on the motion of electricity in wires. In that work, he was the first to derive what we now call the telegrapher`s equations, which describes the propagation of electromagnetic signals along a cable at the speed of light, in some conditions. How was Kirchhoff able to describe electromagnetic propagation as early as 1857, when the notion of displacement current which is believed to be the essential ingredient for the propagation of electric and magnetic fields was not introduced by Maxwell until 1861 and fully explained later in 1865? In this paper, we show that Kirchhoff was the first, in his 1857 paper, to introduce the continuity equation when discussing electromagnetic propagation. We argue that the continuity equation used by Kirchhoff is a more fundamental concept now as it was in 1865 than displacement current. In our view, the dynamics of charged particles can be formulated without invoking fields, but the dynamics of fields cannot be formulated without a continuity equation describing the properties of matter.

physics.hist-ph↗

Glymphatic Clearance in the Optic Nerve: A Multidomain Electro-osmostic Model

Effective metabolic waste clearance and maintaining ionic homeostasis are essential for the health and normal function of the central nervous system. To understand its mechanism and the role of fluid flow, we develop a multidomain electro-osmotic model of optic-nerve microcirculation that couples hydrostatic and osmotic fluid transport with electro-diffusive solute movement across axons, glia, the extracellular space, and arterial/venous/capillary perivascular spaces. Cerebrospinal fluid enters the optic nerve via the arterial parivascular space, passes both the glial and ECS before exiting through the venous parivascular space. Exchanges across astrocytic endfeet are essential and they occur in two distinct and coupled paths: through AQP4 on glial membranes and gaps between glial endfeet, thus establishing a mechanistic substrate for two modes of glymphatic transport, at rest and during stimulus-evoked perturbations. Parameter sweeps show that lowering AQP4-mediated fluid permeability or PVS permeability elevates pressure, suppresses radial exchange and slows clearance, effects most pronounced for solutes reliant on PVS V export. The model reproduces baseline and stimulus-evoked flow and demonstrates that PVS-mediated export is the primary clearance route for both small and moderate solutes. Small molecules clear faster because rapid ECS diffusion broadens their distribution and enhances ECS PVS exchange, whereas moderate species have low ECS diffusivity, depend on transendfoot transfer, and clear more slowly via PVS V convection. Our framework can also be used to explain the sleep-wake effect mechanistically: enlarging ECS volume or permeability increases transinterface flux and accelerates waste removal.

q-bio.CB↗

Multidomain Model for Optic Nerve Potassium Clearance: Roles of Glial Cells and Perivascular Spaces

The accumulation of potassium in the extracellular space surrounding nerve cells is a fundamental aspect of biophysics that has garnered significant attention in recent research. This phenomenon holds implications for various neurological conditions, including spreading depression, migraine, certain types of epilepsy, and potentially, learning processes. A quantitative analysis is essential for understanding the dynamics of potassium clearance following a series of action potentials. This clearance process involves multiple structures along the nerve, including glia, the extracellular space, axons, and the perivascular space, necessitating a spatially distributed systems approach akin to the cable equations of nerve physiology. In this study, we propose a multi-domain model for the optic nerve to investigate potassium accumulation and clearance dynamics. The model accounts for the convection, diffusion, and electrical migration of fluid and ions, revealing the significant roles of glia and the perivascular space in potassium buffering. Specifically, our findings suggest that potassium clearance primarily occurs through convective flow within the syncytia of glia, driven by osmotic pressure differences. Additionally, the perivascular space serves as a crucial pathway for potassium buffering and fluid circulation, further contributing to the overall clearance process. Importantly, our model's adaptability allows for its application to diverse structures with distinct channel and transporter distributions across the six compartments, extending its utility beyond the optic nerve.

physics.bio-ph↗

Displacement Current in Classical and Quantum Systems

It is certain that electrical properties-whether slow (sec) or fast (nsec), even optical (fsec)-are described by Maxwell's equations, and there are terms that depend on the rate of change of the electric and magnetic fields. In particular, Maxwell's equation for the curl of the magnetic field contains both the steady current and a term depending upon the temporal derivative of the electric displacement field. The latter is referred to as displacement current, and is generally believed to have been included originally by Maxwell himself, although there is evidence it was earlier considered by Kirchhoff. Maxwell's equations and Kirchoff's circuit laws both are important over the wide range of frequencies with which electronics traditionally deals. And, displacement current is an important contribution to these in both classical and quantum mechanics. Here, the development of displacement current, its importance in both classical and quantum mechanics, and some applications are provided to illustrate the fundamental role that it plays in the dynamics of a wide range of systems.

physics.class-ph↗

A multi-domain model for microcirculation in optic nerve: blood flow and oxygen transport

Microcirculation of blood and oxygen transport play important roles in biological function of optic nerve and are directly affected by damages or pathologies. This work develops a multi-domain model for optic nerve, that includes important biological structures and various physical mechanisms in blood flow and oxygen delivery. The two sets of vasculature network are treated as five domains in the same geometric region, with various exchanges among them (such as Darcy's law for fluid flow) and with the tissue domain (such as water leak, diffusion). The numerical results of the coupled model for a uniform case of vasculature distribution show mechanisms and scales consistent with literature and intuition. The effects of various important model parameters (relevant to pathological conditions) are investigated to provide insights into the possible implications. The vasculature distribution (resting volume fractions here) has significant impacts on the blood circulation and could lead to insufficient blood supply in certain local region and in turn affect the oxygen delivery. The water leak across the capillary wall will have nontrivial effects after the leak coefficients pass a threshold. The periodic arterial pressure conditions lead to expected periodic patterns and stable spatial profiles, and the uniform case is almost the averaged version of periodic case. The effects of viscosity, the stiffness of blood vessel wall, oxygen demand, etc. have also been analyzed. The framework can be extended to include ionic transport or to study the retina when more biological structural information is available.

physics.bio-ph↗

Coupled Chemical Reactions: Effects of Electric Field, Diffusion and Boundary Control

Chemical reactions involve the movement of charges, and this work presents a mathematical model for describing chemical reactions in electrolytes. The model is developed using an energy variational method that aligns with classical thermodynamics principles. It encompasses both electrostatics and chemical reactions within consistently defined energetic and dissipative functionals. Furthermore, the energy variation method is extended to account for open systems that involve the input and output of charge and mass. Such open systems have the capability to convert one form of input energy into another form of output energy. In particular, a two-domain model is developed to study a reaction system with self-regulation and internal switching, which plays a vital role in the electron transport chain of mitochondria responsible for ATP generation crucial process for sustaining life. Simulations are conducted to explore the influence of electric potential on reaction rates and switching dynamics within the two-domain system. It shows that the electric potential inhibits the oxidation reaction while accelerating the reduction reaction.

physics.chem-ph↗

H-bonds in Crambin: Coherence in an alpha helix

We applied coherence analysis to molecular dynamics simulations of the plant protein crambin, a thionin storage protein found in Abyssinian cabbage. Coherence analysis was developed by engineers to identify linear interactions, without statistical assumptions. Coherence is greater than 0.9 between the displacement of oxygen and nitrogen atoms of H bonds in alpha helices for frequencies between 0.391 GHz and 5.08 GHz (corresponding reciprocally to times of 2.56 ns and 0.197 ns). These H bonds act much like a linear system. Unrelated atoms have uncorrelated motions and much smaller coherence, say 0.02. Groups of atoms (that form a layer of an alpha helix) were averaged and the coherence function of two groups was evaluated. Layers of the alpha helix form a linear system, suggesting that the harmonic analysis of classical molecular dynamics can successfully describe the allosteric interactions of the layers of an alpha helix.

q-bio.BM↗

Kirchhoff's Current Law with Displacement Current

Kirchhoff's Current Law is an essential tool in the design of circuits that operate very quickly, faster than nanoseconds. But Kirchhoff's current is often identified as the flow of particles. The continuity equation or the Maxwell-Ampere law shows that the sum of displacement current $\textbf{plus}$ particle current is conserved by Maxwell's equations and Kirchhoff's law. Kirchoff included the displacement current in the current of his law, from early on. This Kirchhoff current (including the displacement current) does not vary with spatial location in the ionic channels of biology. Electronic circuits switching in nanoseconds are analyzed using the Bohm representation of quantum mechanics including particle and displacement current.

physics.class-ph↗

Mathematical Model for Chemical Reactions in Electrolyte Applied to Cytochrome $c$ Oxidase: an Electro-osmotic Approach

A mathematical model for chemical reactions in electrolytes is developed using an Energy variational method consistent with classical thermodynamics. Electrostatics and chemical reactions are included in properly defined energetic and dissipative functionals. The energy variation method is generalized to deal with open systems with inputs of charge, mass, and energy. The open systems can transform input energy of one type into output energy of another type. The generalized method is used to analyze the conversion of electrical current into proton flow by cytochrome c oxidase, an important enzyme in mitochondria that helps generate the 'energetic currency of life' ATP. The structure of the oxidase guides flows of current and mass that interact according to the energetic and dissipative functionals of the generalized theory. Kirchhoff's current law provides important coupling when the enzyme is in its natural setting in the mitochondrial membrane. The natural function of the enzyme is the result. Electron flows are converted into proton flows and gradients.

physics.chem-ph↗

A Bubble Model for the Gating of Kv Channels

Voltage-gated Kv channels play fundamental roles in many biological processes, such as the generation of the action potential. The gating mechanism of Kv channels is characterized experimentally by single-channel recordings and ensemble properties of the channel currents. In this work, we propose a bubble model coupled with a Poisson-Nernst-Planck (PNP) system to capture the key characteristics, particularly the delay in the opening of channels. The coupled PNP system is solved numerically by a finite-difference method and the solution is compared with an analytical approximation. We hypothesize that the stochastic behaviour of the gating phenomenon is due to randomness of the bubble and channel sizes. The predicted ensemble average of the currents under various applied voltages across the channels is consistent with experimental observations, and the Cole-Moore delay is captured by varying the holding potential.

physics.bio-ph↗

Dielectric Dilemma

A dielectric dilemma faces scientists because Maxwell's equations are poor approximations as usually written, with a single dielectric constant. Maxwell's equations are then not accurate enough to be useful in many applications involving ionic solutions and even solids. The dilemma can be partially resolved by a rederivation of conservation of current, where current is defined now to include the 'polarization of the vacuum' $ε_0 \frac{\partial E}{\partial t}$. Conserveration of current becomes Kirchoff's current law with this definition, in the one dimensional circuits of our electronic technology. With this definition, Kirchoff's laws are valid whenever Maxwell's equations are valid, explaining why those laws are able to describe circuits that switch in nanoseconds.

physics.class-ph↗

Electrical Structure of Biological Cells and Tissues: impedance spectroscopy, stereology, and singular perturbation theory

Impedance Spectroscopy resolves electrical properties into uncorrelated variables, as a function of frequency, with exquisite resolution. Separation is robust and most useful when the system is linear. Impedance spectroscopy combined with appropriate structural knowledge provides insight into pathways for current flow, with more success than other methods. Biological applications of impedance spectroscopy are often not useful since so much of biology is strongly nonlinear in its essential features, and impedance spectroscopy is fundamentally a linear analysis. All cells and tissues have cell membranes and its capacitance is both linear and important to cell function. Measurements proved straightforward in skeletal muscle, cardiac muscle, and lens of the eye. In skeletal muscle, measurements provided the best estimates of the predominant (cell) membrane system that dominates electrical properties. In cardiac muscle, measurements showed definitively that classical microelectrode voltage clamp could not control the potential of the predominant membranes, that were in the tubular system separated from the extracellular space by substantial distributed resistance. In the lens of the eye, impedance spectroscopy changed the basis of all recording and interpretation of electrical measurements and laid the basis for Rae and Mathias extensive later experimental work. Many tissues are riddled with extracellular space as clefts and tubules, for example, cardiac muscle, the lens of the eye, most epithelia, and of course frog muscle. These tissues are best analyzed with a bidomain theory that arose from the work on electrical structure described here. There has been a great deal of work since then on the bi-domain and this represents the most important contribution to biology of the analysis of electrical structure in my view.

q-bio.QM↗