Biology subjects

Marucho, M.

Publications and source records attributed to Marucho, M..

5 recordsLinked to original sources

bioRxiv2022

Theory for weakly polydisperse cytoskeleton filaments

Cytoskeleton filaments have the extraordinary ability to change conformations dynamically in response to alterations of the number density of actins/tubulin, number density and type of binding agents, and electrolyte concentration. This property is crucial for eukaryotic cells to achieve specific biological functions in different cellular compartments. Conventional approaches on biopolymers solution break down for cytoskeleton filaments because they entail several approximations to treat their polyelectrolyte and mechanical properties. In this article, we introduce a novel density functional theory for polydisperse, semiflexible cytoskeleton filaments. The approach accounts for the equilibrium polymerization kinetics, length and orientation filament distributions, as well as the electrostatic interaction between filaments and the electrolyte. This is essential for cytoskeleton polymerization in different cell compartments generating filaments of different lengths, sometimes long enough to become semiflexible. We characterized the thermodynamics properties of actin filaments in electrolyte aqueous solutions. We calculated the free energy, pressure, chemical potential and second virial coefficient for each filament conformation. We also calculated the phase diagram of actin filaments solution and compared with the corresponding results in in-vitro experiments.

neuroscience↗

bioRxiv2022

Hydrodynamic and Polyelectrolyte Properties of Actin Filaments: Theory and Experiments

Actin filaments polyelectrolyte and hydrodynamic properties, their interactions with the biological environment, and external force fields play an essential role in their biological activities in eukaryotic cellular processes. In this article, we introduce a unique approach that combines dynamics and electrophoresis light scattering experiments, an extended semiflexible worm-like chain model, and an asymmetric polymer length distribution theory to characterize the polyelectrolyte and hydrodynamic properties of actin filaments in aqueous electrolyte solutions. A fitting approach was used to optimize the theories and filament models for hydrodynamic conditions. We used the same sample and experimental conditions and considered several g-actin and polymerization buffers to elucidate the impact of their chemical composition, reducing agents, pH values, and ionic strengths on the filament translational diffusion coefficient, electrophoretic mobility, structure factor, asymmetric length distribution, effective filament diameter, electric charge, zeta potential, and semiflexibility. Compared to those values obtained from molecular structure models, our results revealed a lower value of the effective G-actin charge and a more significant value of the effective filament diameter due to the formation of the double layer of the electrolyte surrounding the filaments. Contrary to the data usually reported from electron micrographs, the lower values of our results for the persistence length and average contour filament length agree with the significant difference in the association rates at the filament ends that shift to sub-micro lengths, the maximum of the length distribution.

neuroscience↗

bioRxiv2022

Molecular Structure Study on the Polyelectrolyte Properties of Actin Filaments

An accurate characterization of the polyelectrolyte properties of actin filaments might provide a deeper understanding of the fundamental mechanisms governing the intracellular ionic wave packet propagation in neurons. Infinitely long cylindrical models for actin filaments and approximate electrochemical theories for the electrolyte solutions were recently used to characterize these properties in in vitro and intracellular conditions. This article uses a molecular structure model for actin filaments to investigate the impact of roughness and finite size on the mean electrical potential, ionic density distributions, currents, and conductivities. We solved the electrochemical theories numerically without further approximations. Our findings bring new insights into the electrochemical interactions between a filaments irregular surface charge density and the surrounding medium. The irregular shape of the filament structure model generated pockets, or hot spots, where the current density reached higher or lower magnitudes than those in neighboring areas throughout the filament surface. It also revealed the formation of a well-defined asymmetric electrical double layer with a thickness larger than that commonly used for symmetric models.

neuroscience↗

bioRxiv2021

Electrical impulse characterization along actin filaments in pathological conditions

We present an interactive Mathematica notebook that characterizes the electrical impulses along actin filaments in both muscle and non-muscle cells for a wide range of physiological and pathological conditions. The program is based on a multi-scale (atomic [->] monomer [->] filament) approach capable of accounting for the atomistic details of a protein molecular structure, its biological environment, and their impact on the travel distance, velocity, and attenuation of monovalent ionic wave packets propagating along microfilaments. The interactive component allows investigators to conduct original research by choosing the experimental conditions (intracellular Vs in vitro), nucleotide state (ATP Vs ADP), actin isoform (alpha, gamma, beta, and muscle or non-muscle cell), as well as, a conformation model that covers a variety of mutants and wild-type (the control) actin filament. The simplicity of the theoretical formulation and the high performance of the Mathematica software enable the analysis of multiple conditions without computational restrictions. These studies may provide an unprecedented molecular understanding of why and how age, inheritance, and disease conditions induce dysfunctions in the biophysical mechanisms underlying the propagation of electrical signals along actin filaments.

neuroscience↗

bioRxiv2021

Electrical Propagation of Condensed and Diffuse Ions Along Actin Filaments

In this article, we elucidate the role of divalent ion condensation and high polarization of immobile water molecules in the condensed layer on the propagation of ionic calcium waves along actin filaments. We introduced a novel electrical triple layer model and used a non-linear Debye-Huckel theory with a non-linear, dissipative, electrical transmission line model to characterize the physicochemical properties of each monomer in the filament. This characterization is carried out in terms of an electric circuit model containing monomeric flow resistances and ionic capacitances in both the condensed and diffuse layers. In our studies, we characterized the biocylindrical actin filament model using a high resolution molecular structure. We considered resting and excited states of a neuron using representative mono and divalent electrolyte mixtures. Additionally, we used 0.05V and 0.15V voltage inputs to study ionic waves in voltage clamp experiments on actin filaments. Our results reveal that the physicochemical properties characterizing the condensed and diffuse layers lead to different electrical conduction mediums depending on the ionic species and the neuron state. This region specific propagation mechanism provides a more realistic avenue of delivery by way of cytoskeleton filaments for larger charged cationic species. This new direct path for transporting divalent ions might be crucial for many electrical processes that connect different compartments of the neuron to the soma.

neuroscience↗