SEARCH · Searcharxiv

Results for “q-bio.SC”

Search indexed arXiv papers on artificial intelligence, large language models, computer vision and robotics. Read source abstracts and follow links to arXiv.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 793 records · Page 44Linked to original sources

arXiv2018

Sustainability of environment-assisted energy transfer in quantum photobiological complexes

It is shown that quantum sustainability is a universal phenomenon which emerges during environment-assisted electronic excitation energy transfer (EET) in photobiological complexes (PBCs), such as photosynthetic reaction centers and centers of melanogenesis. We demonstrate that quantum photobiological systems must be sustainable for them to simultaneously endure continuous energy transfer and keep their internal structure from destruction or critical instability. These quantum effects occur due to the interaction of PBCs with their environment which can be described by means of the reduced density operator and effective non-Hermitian Hamiltonian (NH). Sustainable NH models of EET predict the coherence beats, followed by the decrease of coherence down to a small, yet non-zero value. This indicates that in sustainable PBCs, quantum effects survive on a much larger time scale than the energy relaxation of an exciton. We show that sustainable evolution significantly lowers the entropy of PBCs and improves the speed and capacity of EET.

physics.bio-ph↗

arXiv2020

Amperometric Measurements and Dynamic Models Reveal a Mechanism for How Zinc Alters Neurotransmitter Release

Zinc, a suspected potentiator of learning and memory, is shown to affect exocytotic release and storage in neurotransmitter-containing vesicles. Structural and size analysis of the vesicular dense core and halo using transmission electron microscopy was combined with single-cell amperometry to study the vesicle size changes induced after zinc treatment and to compare these changes to theoretical predictions based on the concept of partial release as opposed to full quantal release. This powerful combined analytical approach establishes the existence of an unsuspected strong link between vesicle structure and exocytotic dynamics which can be used to explain the mechanism of regulation of synaptic plasticity by Zn 2+ through modulation of neurotransmitter release.

q-bio.NC↗

arXiv2026

Decoding the Hot-Mitochondrion Paradox

In a 2018 paper and a subsequent article published in 2023, researchers reported that mitochondria maintain temperatures 10oC-15oC higher than the surrounding cytoplasm-a finding that deviates by five to six orders of magnitude from theoretical predictions based on Fourier's law of heat conduction. In 2022, we proposed a solution to this apparent paradox. In the present perspective, we build upon that framework and introduce new ideas to further unravel how a biological membrane-whether of an organelle or a whole cell-can become significantly warmer than its environment. We propose that ion-translocating proteins embedded in the inner mitochondrial membrane (IMM) can be modeled as ratchet engines, introducing a novel, previously overlooked mode of heat transfer. This mechanism, coupled with localized heat release during the cyclical dehydration-translocation-hydration of ions through membrane proteins, may generate transient but substantial temperature spikes. The cumulative thermal occupancy of these microscopic events across the three-dimensional surface of the IMM can account for the elevated temperatures detected by molecular probes.

q-bio.SC↗

arXiv2010

Predictive Modeling of Non-Viral Gene Transfer

In non-viral gene delivery, the variance of transgenic expression stems from the low number of plasmids successfully transferred. Here, we experimentally determine Lipofectamine- and PEI-mediated exogenous gene expression distributions from single cell time-lapse analysis. Broad Poisson-like distributions of steady state expression are observed for both transfection agents, when used with synchronized cell lines. At the same time, co-transfection analysis with YFP- and CFP-coding plasmids shows that multiple plasmids are simultaneously expressed, suggesting that plasmids are delivered in correlated units (complexes). We present a mathematical model of transfection, where a stochastic, two-step process is assumed, with the first being the low-probability entry step of complexes into the nucleus, followed by the subsequent release and activation of a small number of plasmids from a delivered complex. This conceptually simple model consistently predicts the observed fraction of transfected cells, the cotransfection ratio and the expression level distribution. It yields the number of efficient plasmids per complex and elucidates the origin of the associated noise, consequently providing a platform for evaluating and improving non-viral vectors.

q-bio.QM↗

arXiv2012

Macro-scale Topology Optimization for Controlling Internal Shear Stress in a Porous Scaffold Bioreactor

Shear stress is an important physical factor that regulates proliferation, migration and morphogenesis. In particular, the homeostasis of blood vessels is dependent on shear stress. To mimic this process ex vivo, efforts have been made to seed scaffolds with vascular and other cell types in the presence of growth factors and under pulsatile flow conditions. However, the resulting bioreactors lack information on shear stress and flow distributions within the scaffold. Consequently, it is difficult to interpret the effects of shear stress on cell function. Such knowledge would enable researchers to improve upon cell culture protocols. Recent work has focused on optimizing the microstructural parameters of the scaffold to fine tune the shear stress. In this study, we have adopted a different approach whereby flows are redirected throughout the bioreactor along channels patterned in the porous scaffold to yield shear stress distributions that are optimized for uniformity centered on a target value. A topology optimization algorithm coupled to computational fluid dynamics simulations was devised to this end. The channel topology in the porous scaffold was varied using a combination of genetic algorithm and fuzzy logic. The method is validated by experiments using magnetic resonance imaging (MRI) readouts of the flow field.

cond-mat.soft↗

arXiv2020

Analyzing ribosome remodeling in health and disease

regulation largely unexplored, in part due to methodological limitations. Indeed, we review evidence demonstrating that commonly used methods, such as transcriptomics, are inadequate because the variability in mRNAs coding for ribosomal proteins (RP) does not necessarily correspond to RP variability. Thus protein remodeling of ribosomes should be investigated by methods that allow direct quantification of RPs, ideally of isolated ribosomes. We review such methods, focusing on mass spectrometry and emphasizing method-specific biases and approaches to control these biases. We argue that using multiple complementary methods can help reduce the danger of interpreting reproducible systematic biases as evidence for ribosome remodeling.

q-bio.QM↗

arXiv2015

Dynamic Modeling of the Interaction Between Autophagy and Apoptosis in Mammalian Cells

Autophagy is a conserved biological stress response in mammalian cells that is responsible for clearing damaged proteins and organelles from the cytoplasm and recycling their contents via the lysosomal pathway. In cases of mild stress, autophagy acts as a survival mechanism, while in cases of severe stress cells may switch to programmed cell death. Understanding the decision process that moves a cell from autophagy to apoptosis is important since abnormal regulation of autophagy occurs in many diseases, including cancer. To integrate existing knowledge about this decision process into a rigorous, analytical framework, we built a mathematical model of cell fate decisions mediated by autophagy. Our dynamical model is consistent with existing quantitative measurements of autophagy and apoptosis in rat kidney proximal tubular cells responding to cisplatin-induced stress.

q-bio.MN↗

arXiv2011

Cytoskeleton and Cell Motility

The present article is an invited contribution to the Encyclopedia of Complexity and System Science, Robert A. Meyers Ed., Springer New York (2009). It is a review of the biophysical mechanisms that underly cell motility. It mainly focuses on the eukaryotic cytoskeleton and cell-motility mechanisms. Bacterial motility as well as the composition of the prokaryotic cytoskeleton is only briefly mentioned. The article is organized as follows. In Section III, I first present an overview of the diversity of cellular motility mechanisms, which might at first glance be categorized into two different types of behaviors, namely "swimming" and "crawling". Intracellular transport, mitosis - or cell division - as well as other extensions of cell motility that rely on the same essential machinery are briefly sketched. In Section IV, I introduce the molecular machinery that underlies cell motility - the cytoskeleton - as well as its interactions with the external environment of the cell and its main regulatory pathways. Sections IV D to IV F are more detailed in their biochemical presentations; readers primarily interested in the theoretical modeling of cell motility might want to skip these sections in a first reading. I then describe the motility mechanisms that rely essentially on polymerization-depolymerization dynamics of cytoskeleton filaments in Section V, and the ones that rely essentially on the activity of motor proteins in Section VI. Finally, Section VII is devoted to the description of the integrated approaches that have been developed recently to try to understand the cooperative phenomena that underly self-organization of the cell cytoskeleton as a whole.

physics.bio-ph↗

arXiv2010

Geometric and Electromagnetic Aspects of Fusion Pore Making

For regulated exocytosis, we model the morphology and dynamics of the making of the fusion pore or porosome as a cup-shaped lipoprotein structure (a dimple or pit) on the cytosol side of the plasma membrane. We describe the forming of the dimple by a free boundary problem. We discuss the various forces acting and analyze the magnetic character of the wandering electromagnetic field wave produced by intracellular spatially distributed pulsating (and well observed) release and binding of calcium ions anteceding the bilayer membrane vesicle fusion of exocytosis. Our approach explains the energy efficiency of the observed dimple forming prior to hemifusion and fusion pore, and the observed flickering in secretion. It provides a frame to relate characteristic time length of exocytosis to the frequency, amplitude and direction of propagation of the underlying electromagnetic field wave.

math.AP↗

arXiv2018

Formation of autophagosomes coincides with relaxation of membrane curvature

Autophagy is an intracellular degradation process that employs complex membrane dynamics to isolate and break down cellular components. However, many unanswered questions remain concerning remodeling of autophagic membranes. Here, we focus on the advantages of theoretical modelling to study the formation of autophagosomes and to understand the origin of autophagosomal membranes. Starting from the well-defined geometry of final autophagosomes we ask the question of how these organelles can be formed by combining various preautophagosomal membranes such as vesicles, membrane tubules or sheets. We analyse the geometric constraints of autophagosome formation by taking the area of the precursor membranes and their internal volume into account. Our results suggest that vesicle fusion contributes little to the formation of autophagosomes. In the second part we quantify the curvature of the precursors and report that the formation of autophagosomes is associated with a strong relaxation of membrane curvature energy. This effect we find for a wide range of membrane asymmetries. It is especially strong for small distances between both autophagosomal membranes, as observed in vivo. We quantify the membrane bending energies of all precursors by considering membrane asymmetries. We propose that the generation and supply of pre-autophagosomal membranes is one limiting step for autophagosome formation.

q-bio.SC↗

arXiv2025

Using mathematical models of heart cells to assess the safety of new pharmaceutical drugs

Many drugs have been withdrawn from the market worldwide, at a cost of billions of dollars, because of patient fatalities due to them unexpectedly disturbing heart rhythm. Even drugs for ailments as mild as hay fever have been withdrawn due to an unacceptable increase in risk of these heart rhythm disturbances. Consequently, the whole pharmaceutical industry expends a huge effort in checking all new drugs for any unwanted side effects on the heart. The predominant root cause has been identified as drug molecules blocking ionic current flows in the heart. Block of individual types of ionic currents can now be measured experimentally at an early stage of drug development, and this is the standard screening approach for a number of ion currents in many large pharmaceutical companies. However, clinical risk is a complex function of the degree of block of many different types of cardiac ion currents, and this is difficult to understand by looking at results of these screens independently. By using ordinary differential equation models for the electrical activity of heart cells (electrophysiology models) we can integrate information from different types of currents, to predict the effect on whole heart cells and subsequent risk of side effects. The resulting simulations can provide a more accurate summary of the risk of a drug earlier in development and hence more cheaply than the pre-existing approaches.

q-bio.CB↗

arXiv2023

Modeling ionic flow between small targets: insights from diffusion and electro-diffusion theory

The flow of ions through permeable channels causes voltage drop in physiological nanodomains such as synapses, dendrites and dendritic spines, and other protrusions. How the voltage changes around channels in these nanodomains has remained poorly studied. We focus this book chapter on summarizing recent efforts in computing the steady-state current, voltage and ionic concentration distributions based on the Poisson-Nernst-Planck equations as a model of electro-diffusion. We first consider the spatial distribution of an uncharged particle density and derive asymptotic formulas for the concentration difference by solving the Laplace's equation with mixed boundary conditions. We study a constant particles injection rate modeled by a Neumann flux condition at a channel represented by a small boundary target, while the injected particles can exit at one or several narrow patches. We then discuss the case of two species (positive and negative charges) and take into account motions due to both concentration and electrochemical gradients. The voltage resulting from charge interactions is calculated by solving the Poisson's equation. We show how deep an influx diffusion propagates inside a nanodomain, for populations of both uncharged and charged particles. We estimate the concentration and voltage changes in relations with geometrical parameters and quantify the impact of membrane curvature.

cond-mat.soft↗

arXiv2014

Stochastic modeling of cargo transport by teams of molecular motors

Many different types of cellular cargos are transported bidirectionally along microtubules by teams of molecular motors. The motion of this cargo-motors system has been experimentally characterized in vivo as processive with rather persistent directionality. Different theoretical approaches have been suggested in order to explore the origin of this kind of motion. An effective theoretical approach, introduced by Müller et al., describes the cargo dynamics as a tug-of-war between different kinds of motors. An alternative approach has been suggested recently by Kunwar et al., who considered the coupling between motor and cargo in more detail. Based on this framework we introduce a model considering single motor positions which we propagate in continuous time. Furthermore, we analyze the possible influence of the discrete time update schemes used in previous publications on the system's dynamic.

physics.bio-ph↗

arXiv2018

Synthesis for Vesicle Traffic Systems

Vesicle Traffic Systems (VTSs) are the material transport mechanisms among the compartments inside the biological cells. The compartments are viewed as nodes that are labeled with the containing chemicals and the transport channels are similarly viewed as labeled edges between the nodes. Understanding VTSs is an ongoing area of research and for many cells they are partially known. For example, there may be undiscovered edges, nodes, or their labels in a VTS of a cell. It has been speculated that there are properties that the VTSs must satisfy. For example, stability, i.e., every chemical that is leaving a compartment comes back. Many synthesis questions may arise in this scenario, where we want to complete a partially known VTS under a given property. In the paper, we present novel encodings of the above questions into the QBF (quantified Boolean formula) satisfiability problems. We have implemented the encodings in a highly configurable tool and applied to a couple of found-in-nature VTSs and several synthetic graphs. Our results demonstrate that our method can scale up to the graphs of interest.

q-bio.SC↗

arXiv2005

Traffic of Molecular Motors

Molecular motors perform active movements along cytoskeletal filaments and drive the traffic of organelles and other cargo particles in cells. In contrast to the macroscopic traffic of cars, however, the traffic of molecular motors is characterized by a finite walking distance (or run length) after which a motor unbinds from the filament along which it moves. Unbound motors perform Brownian motion in the surrounding aqueous solution until they rebind to a filament. We use variants of driven lattice gas models to describe the interplay of their active movements, the unbound diffusion, and the binding/unbinding dynamics. If the motor concentration is large, motor-motor interactions become important and lead to a variety of cooperative traffic phenomena such as traffic jams on the filaments, boundary-induced phase transitions, and spontaneous symmetry breaking in systems with two species of motors. If the filament is surrounded by a large reservoir of motors, the jam length, i.e., the extension of the traffic jams is of the order of the walking distance. Much longer jams can be found in confined geometries such as tube-like compartments.

cond-mat.stat-mech↗

arXiv2005

Transitions in Microtubule C-termini conformations as a possible Dendritic signaling phenomenon

We model the dynamical states of the C-termini of tubulin dimers that comprise neuronal microtubules. We use molecular dynamics and other computational tools to explore the time-dependent behavior of conformational states of a C-terminus of tubulin within a microtubule and assume that each C-terminus interacts via screened Coulomb forces with the surface of a tubulin dimer, with neighboring C-termini and also with any adjacent microtubule-associated protein 2 (MAP2). Each C-terminus can either bind to the tubulin surface via one of several positively charged regions or can be allowed to explore the space available in the solution surrounding the dimer. We find that the preferential orientation of each C-terminus is away from the tubulin surface but binding to the surface may also take place, albeit at a lower probability. The results of our model suggest that perturbations generated by the C-termini interactions with counter-ions surrounding a MAP2 may propagate over distances greater than those between adjacent microtubules. Thus, the MAP2 structure is able to act as a kind of biological wire (or a cable) transmitting local electrostatic perturbations resulting in ionic concentration gradients from one microtubule to another. We briefly discuss implications the current dynamic modeling may have on synaptic activation and potentiation.

q-bio.SC↗

arXiv2013

Metastable behavior in Markov processes with internal states

A perturbation framework is developed to analyze metastable behavior in stochastic processes with random internal and external states. The process is assumed to be under weak noise conditions, and the case where the deterministic limit is bistable is considered. A general analytical approximation is derived for the stationary probability density and the mean switching time between metastable states, which includes the pre exponential factor. The results are illustrated with a model of gene expression that displays bistable switching. In this model, the external state represents the number of protein molecules produced by a hypothetical gene. Once produced, a protein is eventually degraded. The internal state represents the activated or unactivated state of the gene; in the activated state the gene produces protein more rapidly than the unactivated state. The gene is activated by a dimer of the protein it produces so that the activation rate depends on the current protein level. This is a well studied model, and several model reductions and diffusion approximation methods are available to analyze its behavior. However, it is unclear if these methods accurately approximate long-time metastable behavior (i.e., mean switching time between metastable states of the bistable system). Diffusion approximations are generally known to fail in this regard.

math.AP↗

arXiv2021

Operon Dynamics with State Dependent Transcription and/or Translation Delays

Transcription and translation retrieve and operationalize gene encoded information in cells. These processes are not instantaneous and incur significant delays. In this paper we study Goodwin models of both inducible and repressible operons with state-dependent delays. The paper provides justification and derivation of the model, detailed analysis of the appropriate setting of the corresponding dynamical system, and extensive numerical analysis of its dynamics. Comparison with constant delay models shows significant differences in dynamics that include existence of stable periodic orbits in inducible systems and multistability in repressible systems. A combination of parameter space exploration, numerics, analysis of steady state linearization and bifurcation theory indicates the likely presence of Shilnikov-type homoclinic bifurcations in the repressible operon model.

math.DS↗