scholarly journals A multi-scale approach to describe electrical impulses propagating along actin filaments in both intracellular andin vitroconditions

RSC Advances ◽  
2018 ◽  
Vol 8 (22) ◽  
pp. 12017-12028 ◽  
Author(s):  
Christian Hunley ◽  
Diego Uribe ◽  
Marcelo Marucho
Keyword(s):  
Molecular Structure ◽  
Actin Filaments ◽  
Analytic Solution ◽  
Multi Scale ◽  
Biological Environment ◽  
Electrical Impulses

An innovative analytic solution accounting for the molecular structure, its biological environment, and their impact on electrical impulses along microfilaments.

scholarly journals Electrical impulse characterization along actin filaments in pathological conditions

2021 ◽  
Author(s):  
Christian Hunley ◽  
Md Mohsin ◽  
Marcelo Marucho
Keyword(s):  
Actin Filaments ◽  
High Performance ◽  
Original Research ◽  
Experimental Conditions ◽  
Theoretical Formulation ◽  
Pathological Conditions ◽  
Wide Range ◽  
Biological Environment ◽  
Electrical Impulses

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.

MUFFIN: multi-scale feature fusion for drug–drug interaction prediction

2021 ◽  
Author(s):  
Yujie Chen ◽  
Tengfei Ma ◽  
Xixi Yang ◽  
Jianmin Wang ◽  
Bosheng Song ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Deep Learning ◽  
Medical Information ◽  
Feature Fusion ◽  
Molecular Graph ◽  
Knowledge Graph ◽  
Sequence Information ◽  
Learning Models ◽  
Scale Feature ◽  
Multi Scale

Abstract Motivation Adverse drug–drug interactions (DDIs) are crucial for drug research and mainly cause morbidity and mortality. Thus, the identification of potential DDIs is essential for doctors, patients and the society. Existing traditional machine learning models rely heavily on handcraft features and lack generalization. Recently, the deep learning approaches that can automatically learn drug features from the molecular graph or drug-related network have improved the ability of computational models to predict unknown DDIs. However, previous works utilized large labeled data and merely considered the structure or sequence information of drugs without considering the relations or topological information between drug and other biomedical objects (e.g. gene, disease and pathway), or considered knowledge graph (KG) without considering the information from the drug molecular structure. Results Accordingly, to effectively explore the joint effect of drug molecular structure and semantic information of drugs in knowledge graph for DDI prediction, we propose a multi-scale feature fusion deep learning model named MUFFIN. MUFFIN can jointly learn the drug representation based on both the drug-self structure information and the KG with rich bio-medical information. In MUFFIN, we designed a bi-level cross strategy that includes cross- and scalar-level components to fuse multi-modal features well. MUFFIN can alleviate the restriction of limited labeled data on deep learning models by crossing the features learned from large-scale KG and drug molecular graph. We evaluated our approach on three datasets and three different tasks including binary-class, multi-class and multi-label DDI prediction tasks. The results showed that MUFFIN outperformed other state-of-the-art baselines. Availability and implementation The source code and data are available at https://github.com/xzenglab/MUFFIN.

Multiscale Modeling Techniques Based on Molecular Structure and Elastic Properties

2013 ◽  
Vol 312 ◽  
pp. 438-441
Author(s):  
Jiu Li
Keyword(s):  
Molecular Structure ◽  
Force Field ◽  
Elastic Properties ◽  
Polymer Structure ◽  
Structure And Properties ◽  
Basic Principles ◽  
Multi Scale ◽  
Scale Modeling ◽  
Modeling Techniques ◽  
Nonlinear Continuum

Based on the principle of using atomistic force field, and the use of ultra-flexible multi-scale modeling techniques to predict the polycarbonate and polyimide polymer molecular structure and the elastic properties of the system. The model combines molecular modeling and nonlinear continuum mechanics basic principles, to simulate and predict the behavior of the material properties of the polymer molecular structure. For the polymer structure and properties, using a plurality of force field simulation to predict the contrast, and binding experiments measured polymer performance value, using static and dynamic molecular simulation technology for molecular mechanics energy minimization to solve.

scholarly journals The molecular structure of primary cilia revealed by cryo-electron tomography

2020 ◽  
Author(s):  
Petra Kiesel ◽  
Gonzalo Alvarez Viar ◽  
Nikolai Tsoy ◽  
Riccardo Maraspini ◽  
Alf Honigmann ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Primary Cilium ◽  
Actin Filaments ◽  
Primary Cilia ◽  
Electron Tomography ◽  
3D Structure ◽  
Molecular Composition ◽  
Structural Investigations ◽  
Cryo Electron Tomography ◽  
Motile Cilia

AbstractPrimary cilia are microtubule-based organelles involved in key signaling and sensing processes in eukaryotic cells. Unlike motile cilia, which have been thoroughly studied, the structure and the composition of primary cilia remain largely unexplored despite their fundamental role in development and homeostasis. They have for long been falsely regarded as simplified versions of motile cilia because they lack distinctive elements such as dynein arms, radial spokes, and central pair complex. However, revealing the detailed molecular composition and 3D structure of primary cilia is necessary in order to understand the mechanisms that govern their functions. Such structural investigations are so far being precluded by the challenging preparation of primary cilia for cryo-electron microscopy. Here, we developed an enabling method for investigating the structure of primary cilia at molecular resolution by cryo-electron tomography. We show that the well-known “9+0” arrangement of microtubule doublets is present only at the base of the primary cilium. A few microns away from the base the ciliary architecture changes into an unstructured bundle of EB1-decorated microtubule singlets and some actin filaments. Our results suggest the existence of a previously unobserved crosstalk between actin filaments and microtubules in the primary cilium. Our work provides unprecedented insights into the molecular structure of primary cilia and a general framework for uncovering their molecular composition and function in health and disease. This opens up new possibilities to study aspects of this important organelle that have so far been out of reach.

scholarly journals Molecular Structure Study on the Polyelectrolyte Properties of Actin Filaments

2022 ◽  
Author(s):  
Santiago M Bedoya ◽  
Marcelo Marucho
Keyword(s):  
Molecular Structure ◽  
Actin Filaments ◽  
Surrounding Medium ◽  
Electrical Potential ◽  
Finite Size ◽  
Electrolyte Solutions ◽  
Structure Study ◽  
Structure Model ◽  
The Impact

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 filament′s 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.

scholarly journals The cytoskeletal architecture of the presynaptic terminal and molecular structure of synapsin 1.

1989 ◽  
Vol 108 (1) ◽  
pp. 111-126 ◽  
Author(s):  
N Hirokawa ◽  
K Sobue ◽  
K Kanda ◽  
A Harada ◽  
H Yorifuji
Keyword(s):  
Molecular Structure ◽  
Actin Filaments ◽  
Synaptic Vesicles ◽  
Plasma Membranes ◽  
Electric Organ ◽  
Main Element ◽  
Spherical Head ◽  
Spherical Structures ◽  
Synapsin 1

We have examined the cytoskeletal architecture and its relationship with synaptic vesicles in synapses by quick-freeze deep-etch electron microscopy (QF.DE). The main cytoskeletal elements in the presynaptic terminals (neuromuscular junction, electric organ, and cerebellar cortex) were actin filaments and microtubules. The actin filaments formed a network and frequently were associated closely with the presynaptic plasma membranes and active zones. Short, linking strands approximately 30 nm long were found between actin and synaptic vesicles, between microtubules and synaptic vesicles. Fine strands (30-60 nm) were also found between synaptic vesicles. Frequently spherical structures existed in the middle of the strands between synaptic vesicles. Another kind of strand (approximately 100 nm long, thinner than the actin filaments) between synaptic vesicles and plasma membranes was also observed. We have examined the molecular structure of synapsin 1 and its relationship with actin filaments, microtubules, and synaptic vesicles in vitro using the low angle rotary shadowing technique and QF.DE. The synapsin 1, approximately 47 nm long, was composed of a head (approximately 14 nm diam) and a tail (approximately 33 nm long), having a tadpole-like appearance. The high resolution provided by QF.DE revealed that a single synapsin 1 cross-linked actin filaments and linked actin filaments with synaptic vesicles, forming approximately 30-nm short strands. The head was on the actin and the tail was attached to the synaptic vesicle or actin filament. Microtubules were also cross-linked by a single synapsin 1, which also connected a microtubule to synaptic vesicles, forming approximately 30 nm strands. The spherical head was on the microtubules and the tail was attached to the synaptic vesicles or to microtubules. Synaptic vesicles incubated with synapsin 1 were linked with each other via fine short fibrils and frequently we identified spherical structures from which two or three fibril radiated and cross-linked synaptic vesicles. We have examined the localization of synapsin 1 using ultracryomicrotomy and colloidal gold-immunocytochemistry of anti-synapsin 1 IgG. Synapsin 1 was exclusively localized in the regions occupied by synaptic vesicles. Statistical analyses indicated that synapsin 1 is located mostly at least approximately 30 nm away from the presynaptic membrane. These data derived via three different approaches suggest that synapsin 1 could be a main element of short linkages between actin filaments and synaptic vesicles, and between microtubules and synaptic vesicles, and between synaptic vesicles in the nerve terminals.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Stereocilia Rootlets: Actin-Based Structures That Are Essential for Structural Stability of the Hair Bundle

2020 ◽  
Vol 21 (1) ◽  
pp. 324 ◽  
Author(s):  
Itallia Pacentine ◽  
Paroma Chatterjee ◽  
Peter G. Barr-Gillespie
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Actin Filaments ◽  
Hair Bundle ◽  
Sensory Hair ◽  
Sensory Hair Cells ◽  
Associated Proteins ◽  
Unique Manner ◽  
Electrical Impulses ◽  
Mechanical Movement

Sensory hair cells of the inner ear rely on the hair bundle, a cluster of actin-filled stereocilia, to transduce auditory and vestibular stimuli into electrical impulses. Because they are long and thin projections, stereocilia are most prone to damage at the point where they insert into the hair cell’s soma. Moreover, this is the site of stereocilia pivoting, the mechanical movement that induces transduction, which additionally weakens this area mechanically. To bolster this fragile area, hair cells construct a dense core called the rootlet at the base of each stereocilium, which extends down into the actin meshwork of the cuticular plate and firmly anchors the stereocilium. Rootlets are constructed with tightly packed actin filaments that extend from stereocilia actin filaments which are wrapped with TRIOBP; in addition, many other proteins contribute to the rootlet and its associated structures. Rootlets allow stereocilia to sustain innumerable deflections over their lifetimes and exemplify the unique manner in which sensory hair cells exploit actin and its associated proteins to carry out the function of mechanotransduction.

Electron Microscopy of Cytoplasmic Contractile Proteins

1978 ◽  
Vol 36 (3) ◽  
pp. 606-614 ◽  
Author(s):  
T.D. Pollard ◽  
P. Maupin
Keyword(s):  
Electron Microscopy ◽  
Actin Filaments ◽  
Three Dimensional ◽  
Uranyl Acetate ◽  
Contractile Proteins ◽  
Dimensional Structure ◽  
X Ray Diffraction ◽  
Cytoplasmic Matrix ◽  
Computer Image Processing ◽  
Nonmuscle Cells

In this paper we review some of the contributions that electron microscopy has made to the analysis of actin and myosin from nonmuscle cells. We place particular emphasis upon the limitations of the ultrastructural techniques used to study these cytoplasmic contractile proteins, because it is not widely recognized how difficult it is to preserve these elements of the cytoplasmic matrix for electron microscopy. The structure of actin filaments is well preserved for electron microscope observation by negative staining with uranyl acetate (Figure 1). In fact, to a resolution of about 3nm the three-dimensional structure of actin filaments determined by computer image processing of electron micrographs of negatively stained specimens (Moore et al., 1970) is indistinguishable from the structure revealed by X-ray diffraction of living muscle.

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