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 simplicity of the theoretical formulation, and high performance of the Mathematica software, enable the analysis of multiple conditions without computational restrictions. 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 choose 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. We used the computational tool to analyze environmental changes such as temperature effects and pH changes of the surrounding solutions, as well as structural changes to an actin monomer due to radius changes. Additionally, we investigated for the first time the electrostatic consequences of actin mutations from different disease conditions. 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.

Electrical Propagation of Condensed and Diffuse Ions Along Actin Filaments.

In this article, we elucidate the roles of divalent ion condensation and highly polarized immobile water molecules 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. 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 along actin filaments in voltage clamp experiments. Our results reveal that the physicochemical properties characterizing the condensed and diffuse layers lead to different electrical conductive 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. A new direct path for transporting divalent ions might be crucial for many electrical processes found in localized neuron elements such as at mitochondria and dendritic spines.

A multi-scale approach to describe electrical impulses propagating along actin filaments in both intracellular and in vitro conditions.

An accurate and efficient characterization of the polyelectrolyte properties for cytoskeleton filaments are key to the molecular understanding of electrical signal propagation, bundle and network formation, as well as their potential nanotechnological applications. In this article, we introduce an innovative multi-scale approach able to account for the atomistic details of a protein molecular structure, its biological environment, and their impact on electrical impulses propagating along wild type Actin filaments. The formulation includes non trivial contributions to the ionic electrical conductivity and capacitance coming from the diffuse part of the electrical double layer of G-actins. We utilize this monomer characterization in a nonlinear inhomogeneous transmission line prototype model to account for the monomer-monomer interactions, dissipation and damping perturbations along the filament length. A novel, simple, accurate, approximate analytic expression has been obtained for the transmission line model. Our results reveal the propagation of electrical signal impulses in the form of solitons for the range of voltage stimulus and electrolyte solutions typically present for intracellular and in-vitro conditions. The approach predicts a lower electrical conductivity with higher linear capacitance and nonlinear accumulation of charge for intracellular conditions. Our results show a significant influence of the voltage input on the electrical impulse shape, attenuation and kern propagation velocity. The filament is able to sustain the soliton propagation at almost constant kern velocity for the in-vitro condition, whereas the intracellular condition displays a remarkable deceleration. Additionally, the solitons are narrower and travel faster at higher voltage input. As a unique feature, this multi-scale theory is able to account for molecular structure conformation (mutation) and biological environment (protonations/deprotonations) changes often present in pathological conditions. It is also applicable to other highly charged rod-like polyelectrolytes with relevance in biomedicine and biophysics.

Electrical double layer properties of spherical oxide nanoparticles.

The accurate characterization of the electrical double layer properties of nanoparticles is of fundamental importance for optimizing their physicochemical properties for specific biotechnological and biomedical applications. In this article, we use classical solvation density functional theory and a surface complexation model to investigate the effects of the pH and the nanoparticle size on the structural and electrostatic properties of an electrolyte solution surrounding a spherical silica oxide nanoparticle. The formulation has been particularly useful for identifying dominant interactions governing the ionic driving force at a variety of pH levels and nanoparticle sizes. As a result of the energetic interplay displayed between electrostatic potential, ion-ion correlation and particle crowding effects on the nanoparticle surface titration, rich, non-trivial ion density profiles and mean electrostatic potential behavior have been found.