Transient Response of the Acid-base Diode for Polarity Change

An application of the so-called acid-base diode would be the sensitive detection of nonhydrogen cations in an acidic medium based on salt-effects. For diode purposes different connecting elements between the acidic and aqueous reservoirs of the diode were developed, namely a polyvinyl alcohol (PVA) hydrogel cylinder, and a polyvinyl butyral (PVB) membrane. During the measurement of the voltage – current characteristic (VCC) of the diode, it was found, that in the case of PVA gel cylinder an overshoot (a local maximum followed by a local minimum) appeared in the time vs. current curve, while the diode was switched between modes (open or closed), that is the direction of the applied voltage was reversed. The overshoot did not appear in PVB membrane.The existence of overshoots was studied by numerical simulations. The time response of the diode with different hypothetic connecting elements was investigated, when the diode was switched between modes via changing the polarity of applied voltage. We found that larger diffusion coefficients of hydrogen and hydroxide ions explain the appearance of overshoots. By examining the concentration and potential profiles a qualitative explanation of this phenomenon was given

Adaptive moving mesh algorithm based on local reaction rate

An empirical mesh adaption algorithm is introduced for modeling one-dimensional reaction-diffusion systems with large moving gradients. Our new algorithm is based on the revelation, that in reaction-diffusion systems the high moving concentration gradients appear nearby to the region where the rate of reaction is maximal, thus the local reaction rate can be used to control the mesh adaption. We found, that the main advantage of such a method is its simplicity and easy implementation. As an example we study an acid-base diode, where large moving gradients appear. The mathematical model of the diode contains several parabolic PDEs, coupled with one elliptic PDE. An r-refinement technique is used and attached to the commercial finite element solver COMSOL. We investigated the time-dependent salt effects of the diode with our developed algorithm. Our mesh adaption method is advantageous for modeling of any reaction-diffusion systems with localized high concentration gradients

Molecular Dynamics Simulation

Condensed matter systems, ranging from simple fluids and solids to complex multicomponent materials and even biological matter, are governed by well understood laws of physics, within the formal theoretical framework of quantum theory and statistical mechanics. On the relevant scales of length and time, the appropriate ‘first-principles’ description needs only the Schroedinger equation together with Gibbs averaging over the relevant statistical ensemble. However, this program cannot be carried out straightforwardly—dealing with electron correlations is still a challenge for the methods of quantum chemistry. Similarly, standard statistical mechanics makes precise explicit statements only on the properties of systems for which the many-body problem can be effectively reduced to one of independent particles or quasi-particles. [...

Cell mechanics in flow: algorithms and applications

The computer simulations are pervasively used to improve the knowledge about biophysical phenomena and to quantify effects which are difficult to study experimentally. Generally, the numerical methods and models are desired to be as accurate as possible on the chosen length and time scales, but, at the same time, affordable in terms of computations. Until recently, the cell mechanics and blood flow phenomena on the sub-micron resolution could not be rigorously studied using computer simulations. However, within the last decade, advances in methods and hardware catalyzed the development of models for cells mechanics and blood flow modeling which, previously, were considered to be not feasible. In this context, a model should accurately describe a phenomenon, be computationally affordable, and be flexible to be applied to study different biophysical changes. This thesis focuses on the development of the new methods, models, and high-performance software implementation that expand the class of problems which can be studied numerically using particle-based methods. Microvascular networks have complex geometry, often without any symmetry, and to study them we need to tackle computational domains with several inlets and outlets. However, an absence of appropriate boundary conditions for particle- based methods hampers study of the blood flow in these domains. Another obstacle to model complex blood flow problems is the absence the highperformance software. This problem restricts the applicability of the of particlebased cell flow models to relatively small systems. Although there are several validated red blood cell models, to date, there are no models for suspended eukaryotic cells. The present thesis addresses these issues. We introduce new open boundary conditions for particle-based systems and apply them to study blood flow in a part of a microvascular network. We develop a software demonstrating outstanding performance on the largest supercomputers and used it to study blood flow in microfluidic devices. Finally, we present a new eukaryotic cell model which helps in quantifying the effect of sub-cellular components on the cell mechanics during deformations in microfluidic devices

Computational modeling of biological nanopores

Throughout our history, we, humans, have sought to better control and understand our environment. To this end, we have extended our natural senses with a host of sensors-tools that enable us to detect both the very large, such as the merging of two black holes at a distance of 1.3 billion light-years from Earth, and the very small, such as the identification of individual viral particles from a complex mixture. This dissertation is devoted to studying the physical mechanisms that govern a tiny, yet highly versatile sensor: the biological nanopore. Biological nanopores are protein molecules that form nanometer-sized apertures in lipid membranes. When an individual molecule passes through this aperture (i.e., "translocates"), the temporary disturbance of the ionic current caused by its passage reveals valuable information on its identity and properties. Despite this seemingly straightforward sensing principle, the complexity of the interactions between the nanopore and the translocating molecule implies that it is often very challenging to unambiguously link the changes in the ionic current with the precise physical phenomena that cause them. It is here that the computational methods employed in this dissertation have the potential to shine, as they are capable of modeling nearly all aspects of the sensing process with near atomistic precision. Beyond familiarizing the reader with the concepts and state-of-the-art of the nanopore field, the primary goals of this dissertation are fourfold: (1) Develop methodologies for accurate modeling of biological nanopores; (2) Investigate the equilibrium electrostatics of biological nanopores; (3) Elucidate the trapping behavior of a protein inside a biological nanopore; and (4) Mapping the transport properties of a biological nanopore. In the first results chapter of this thesis (Chapter 3), we used 3D equilibrium simulations [...]Comment: PhD thesis, 306 pages. Source code available at https://github.com/willemsk/phdthesis-tex

Modeling and Simulation of Lipid Membranes

Cell membranes are complex structures able to contain the main elements of the cell and to protect them from the external surroundings, becoming the most fundamental interface in Biology. The main subject of this book is the study of the structure and characteristics of lipid membranes in a wide variety of environments, ranging from simple phospholipid membranes to complex systems including proteins, peptides, or oncogenes as well as the analysis of the interactions of the membrane components with small molecules and drugs. The scope of this book is to provide recent developments on membrane structure, composition and function by means of theoretical and experimental techniques, some of them combining computer simulations with available data obtained at the laboratory.This Special Issue aims to report brand new key contributions to the field and also to give an overview about the connection between experiments and computer simulations, addressing fundamental aspects and applied research in biological membranes, with particular attention paid to the applications of computer modeling and simulation to medicine

The Mechanisms And Roles Of Feedback Loops For Visual Processing

Signal flow in the brain is not unidirectional; feedback represents a key element in neural signal processing. To address the question on how do neural feedback loops work in terms of synapses, microcircuitry, and systems dynamics, we developed a chick midbrain slice preparation to study and characterize one important feedback loop within the avian visual system: isthmotectal feedbackloop. The isthmotectal feedback loop consists of the optic tectum: OT) and three nucleus isthmi: Imc, Ipc and SLu. The tectal layer 10 neurons project to ipsilateral Imc, Ipc and SLu in a topographic way. In turn Ipc and SLu send back topographical: local) cholinergic terminals to the OT, whereas Imc sends non-topographical: global) GABAergic projections to the OT, and also to the Ipc and the SLu. We first study the cellular properties of Ipc neurons and found that almost all Ipc cells exhibited spontaneous activity characterized with a barrage of EPSPs and occasional spikes. Further experiments reveal the involvement of GABA in mediating the spontaneous synaptic inputs to the Ipc neurons. Next we investigate the mechanisms of oscillatory bursting in Ipc, which is observed in vivo, by building a model network based on the in vitro experimental results. Our simulation results conclude that strong feedforward excitation and spike-rate adaptation can generate oscillatory bursting in Ipc neuron in response to a constant input. Then we consider the effect of distributed synaptic delays measured within the isthmotectal feedback loop and elucidate that distributed delays can stabilize the system and lead to an increased range of parameters for which the system converges to a stable fixed point. Next we explore the functional features of GABAergic projection from Imc to Ipc and find that Imc has a regulatory role on actions of Ipc neurons in that stimulating Imc can evoke action potentials in Ipc neurons while it also can suppress the firing in Ipc neurons which is generated by somatic current injection. The mechanism of regulatory action is further studied by a two-compartment neuron model. Last, we lay out several open questions in this area which may worth further investigation

Transient intra- and extra-cellular thermometry as probes of thermogenesis

Temperature is a fundamental thermodynamic property affecting every biochemical reaction in cellular milieu. Thermometry in tissues has proven useful in understanding thermoregulatory neuronal circuits and cancer metabolism. In contrast, intracellular temperature changes are relatively less explored. Theoretical temperature changes in intracellular organelles are widely debated, due to lack of understanding of intracellular thermal resistances. There is thus a need for thermometry techniques that can probe within a cell. Such intracellular thermometry can inform theory, and more importantly, provide insight into the role of temperature as a physiological parameter in intracellular studies. In this work, we describe an intracellular thermometry technique developed using silicon-based microelectromechanical techniques. We fabricated a 5 μm wide micro-thermocouple probe that has a calibration accuracy of 1% and a time constant of 32 μs. Through this probe, we measured transient temperature changes during stimulated mitochondrial proton uncoupling in neurons of Aplysia californica. We find that a transient proton motive force dissipation is more dominant than steady-state substrate oxidation in stimulated thermogenesis. Our measurements demonstrate the utility of transient intracellular thermometry in better understanding the thermochemistry of stimulated mitochondrial metabolism. Using insights from intracellular thermometry, we theoretically examine the validity of thermal conductivity approximation and find that the thermal interfacial resistances might dominate in the sub-cellular region. We develop a generalized thermal resistance network model to analyze cellular-level temperature changes. We find that intracellular temperature changes could be useful to probe stimulated transient biochemical reactions that can produce higher intracellular temperatures, which may not occur endogenously. On the other hand, to probe endogenously thermogenic reactions, we find extracellular thermometry to be better suited, especially at length-scales > 1 cm, such as tissues or organs. To this end, we develop a wireless temperature measurement technique using magnetostriction based sensors that can potentially measure temperatures at tissues length-scales remotely. We identify material properties that influence temperature sensitivity and demonstrate a 5-fold improvement through optimal selection. We further develop techniques that reduce instrument complexity and discuss ways to miniaturize wireless sensors. Overall, this work advances intra- and extra-cellular thermometry techniques that potentially provide unprecedented insight into thermogenesis in cells