by Keyword: simulation
Bodrenko, I, Ceccarelli, M, Acosta-Gutierrez, S, (2023). The mechanism of an electrostatic nanofilter: overcoming entropy with electrostatics Physical Chemistry Chemical Physics 25, 26497-26506
General porins are nature's sieving machinery in the outer membrane of Gram-negative bacteria. Their unique hourglass-shaped architecture is highly conserved among different bacterial membrane proteins and other biological channels. These biological nanopores have been designed to protect the interior of the bacterial cell from leakage of toxic compounds while selectively allowing the entry of the molecules needed for cell growth and function. The mechanism of transport through porins is of utmost and direct interest for drug discovery, extending toward nanotechnology applications for blue energy, separations, and sequencing. Here we present a theoretical framework for analysing the filter of general porins in relation to translocating molecules with the aid of enhanced molecular simulations quantitatively. Using different electrostatic probes in the form of a series of related molecules, we describe the nature of this filter and how to finely tune permeability by exploiting electrostatic interactions between the pore and the translocating molecule. Eventually, we show how enhanced simulations constitute today a valid tool for characterising the mechanism and quantifying energetically the transport of molecules through nanopores. General porins are nature's sieving machinery in the outer membrane of Gram-negative bacteria. In the diffusive transport process of molecules, electrostatic interactions can help to decrease the entropic free energy barrier.
JTD Keywords: Channel, Diffusion barrier, Electric-field, Molecular-dynamics, Outer-membrane permeability, Permeation, Porins, Simulations, Translocation, Transport
Ferre-Torres J, Noguera-Monteagudo A, Lopez-Canosa A, Romero-Arias JR, Barrio R, Castaño O, Hernandez-Machado A, (2023). Modelling of chemotactic sprouting endothelial cells through an extracellular matrix Frontiers In Bioengineering And Biotechnology 11, 1145550
Sprouting angiogenesis is a core biological process critical to vascular development. Its accurate simulation, relevant to multiple facets of human health, is of broad, interdisciplinary appeal. This study presents an in-silico model replicating a microfluidic assay where endothelial cells sprout into a biomimetic extracellular matrix, specifically, a large-pore, low-concentration fibrin-based porous hydrogel, influenced by chemotactic factors. We introduce a novel approach by incorporating the extracellular matrix and chemotactic factor effects into a unified term using a single parameter, primarily focusing on modelling sprouting dynamics and morphology. This continuous model naturally describes chemotactic-induced sprouting with no need for additional rules. In addition, we extended our base model to account for matrix sensing and degradation, crucial aspects of angiogenesis. We validate our model via a hybrid in-silico experimental method, comparing the model predictions with experimental results derived from the microfluidic setup. Our results underscore the intricate relationship between the extracellular matrix structure and angiogenic sprouting, proposing a promising method for predicting the influence of the extracellular matrix on angiogenesis.Copyright © 2023 Ferre-Torres, Noguera-Monteagudo, Lopez-Canosa, Romero-Arias, Barrio, Castaño and Hernandez-Machado.
JTD Keywords: angiogenesis, biomimmetic, chemotaxis, endothelial cells, filopodia, growth, in silico model, mathematical models, mechanisms, metalloproteinase, migration, morphogenesis, phase field, pore-size, simulation, Angiogenesis, Biomimmetic, Chemotaxis, Endothelial cells, Extracellular matrix, In silico model, Mathematical models, Phase field, Tip cells
Milenkovic, Stefan, Wang, Jiajun, Acosta-Gutierrez, Silvia, Winterhalter, Mathias, Ceccarelli, Matteo, Bodrenko, Igor V., (2023). How the physical properties of bacterial porins match environmental conditions Physical Chemistry Chemical Physics 25, 12712-12722
Despite the high homology of OmpF and OmpC, the internally folded loop responds differently to temperature increase.
JTD Keywords: diffusion, mechanism, molecules, nanopores, permeability, proteins, rules, simulations, transport, Membrane
Tampieri, Francesco, Espona-Noguera, Albert, Labay, Cédric, Ginebra, Maria-Pau, Yusupov, Maksudbek, Bogaerts, Annemie, Canal, Cristina, (2023). Does non-thermal plasma modify biopolymers in solution? A chemical and mechanistic study for alginate Biomaterials Science 11, 4845-4858
The mutual interaction between reactive species generated by non-thermal plasma and biopolymers in solution causes oxidative modifications that can have an impact in biomedical applications.
JTD Keywords: atmospheric plasma, cellulose, dftb3, gas, oxidation, parameterization, simulations, water, Molecular-dynamics
Venugopal A, Ruiz-Perez L, Swamynathan K, Kulkarni C, Calò A, Kumar M, (2023). Caught in Action: Visualizing Dynamic Nanostructures Within Supramolecular Systems Chemistry Angewandte Chemie 62, e202208681
Supramolecular systems chemistry has been an area of active research to develop nanomaterials with life-like functions. Progress in systems chemistry relies on our ability to probe the nanostructure formation in solution. Often visualizing the dynamics of nanostructures which transform over time is a formidable challenge. This necessitates a paradigm shift from dry sample imaging towards solution-based techniques. We review the application of state-of-the-art techniques for real-time, in situ visualization of dynamic self-assembly processes. We present how solution-based techniques namely optical super-resolution microscopy, solution-state atomic force microscopy, liquid-phase transmission electron microscopy, molecular dynamics simulations and other emerging techniques are revolutionizing our understanding of active and adaptive nanomaterials with life-like functions. This Review provides the visualization toolbox and futuristic vision to tap the potential of dynamic nanomaterials.© 2022 Wiley-VCH GmbH.
JTD Keywords: electron-microscopy, fluorescence microscopy, in-situ, mechanical-properties, molecular simulations, nanostructures, polymerization, polymers, stimulated-emission, super-resolution microscopy, supramolecular chemistry, systems chemistry, water, Atomic-force microscopy, Liquid tem, Nanostructures, Super-resolution microscopy, Supramolecular chemistry, Systems chemistry
Tuveri, GM, Ceccarelli, M, Pira, A, Bodrenko, IV, (2022). The Optimal Permeation of Cyclic Boronates to Cross the Outer Membrane via the Porin Pathway Antibiotics 11, 840
We investigated the diffusion of three cyclic boronates formulated as beta-lactamase inhibitors through the porin OmpF to evaluate their potential to cross OM via the porin pathway. The three nonbeta-lactam molecules diffuse through the porin eyelet region with the same mechanism observed for beta-lactam molecules and diazobicyclooctan derivatives, with the electric dipole moment aligned with the transversal electric field. In particular, the BOH group can interact with both the basic ladder and the acidic loop L3, which is characteristic of the size-constricted region of this class of porins. On one hand, we confirm that the transport of small molecules through enterobacter porins has a common general mechanism; on the other, the class of cyclic boronate molecules does not seem to have particular difficulties in diffusing through enterobacter porins, thus representing a good scaffold for new anti-infectives targeting Gram-negative bacteria research.
JTD Keywords: beta-lactamase inhibitors, cyclic boronates, diffusion current, metadynamics, molecular dynamics simulations, permeation, Antibiotics, Beta-lactamase inhibitors, Cyclic boronates, Diffusion, Diffusion current, Discovery, Electric-field, Metadynamics, Molecular dynamics simulations, Molecular-dynamics simulations, Nanopores, Permeability, Permeation, Porins, Rules, Translocation
Martí D, Martín-Martínez E, Torras J, Betran O, Turon P, Alemán C, (2022). In silico study of substrate chemistry effect on the tethering of engineered antibodies for SARS-CoV-2 detection: Amorphous silica vs gold Colloids And Surfaces B-Biointerfaces 213, 112400
The influence of the properties of different solid substrates on the tethering of two antibodies, IgG1-CR3022 and IgG1-S309, which were specifically engineered for the detection of SARS-CoV-2, has been examined at the molecular level using conventional and accelerated Molecular Dynamics (cMD and aMD, respectively). Two surfaces with very different properties and widely used in immunosensors for diagnosis, amorphous silica and the most stable facet of the face-centered cubic gold structure, have been considered. The effects of such surfaces on the structure and orientation of the immobilized antibodies have been determined by quantifying the tilt and hinge angles that describe the orientation and shape of the antibody, respectively, and the dihedrals that measure the relative position of the antibody arms with respect to the surface. Results show that the interactions with amorphous silica, which are mainly electrostatic due to the charged nature of the surface, help to preserve the orientation and structure of the antibodies, especially of the IgG1-CR3022, indicating that the primary sequence of those antibodies also plays some role. Instead, short-range van der Waals interactions with the inert gold surface cause a higher degree tilting and fraying of the antibodies with respect to amorphous silica. The interactions between the antibodies and the surface also affect the correlation among the different angles and dihedrals, which increases with their strength. Overall, results explain why amorphous silica substrates are frequently used to immobilize antibodies in immunosensors. © 2022 The Authors
JTD Keywords: amorphous silica, antibody immobilization, enzyme, gol d, gold, immobilization, immunosensor, molecu l a r dynamics, molecular dynamics, protein adsorption, sars-cov-2 immunosensor, simulations, spike protein, surface interactions, target, vaccine, Amorphous silica, Antibodies, Antibody engineering, Antibody immobilization, Antibody structure, Article, Chemical detection, Computer model, Controlled study, Dihedral angle, Gold, In-silico, Molecular dynamics, Molecular levels, Molecular-dynamics, Nonhuman, Property, Sars, Sars-cov-2 immunosensor, Severe acute respiratory syndrome coronavirus 2, Silica, Silico studies, Silicon dioxide, Solid substrates, Structure analysis, Substrate chemistry, Substrates, Van der waals forces, Virus detection
McGill, Kris, Sackley, Catherine, Godwin, Jon, Gavaghan, David, Ali, Myzoon, Ballester, Belen Rubio, Brady, Marian C, Brady, M.C, Ali, M, Ashburn, A, Barer, D, Barzel, A, Bernhardt, J, Bowen, A, Drummond, A, Edmans, J, English, C, Gladman, J, Godecke, E, Hiekkala, S, Hoffman, T, Kalra, L, Kuys, S, Langhorne, P, Laska, A.C, Lees, K, Logan, P, Machner, B, Mead, G, Morris, J, Pandyan, A, Pollock, A, Pomeroy, V, Rodgers, H, Sackley, C, Shaw, L, Stott, D.J, Sunnerhagen, K.S, Tyson, S, van Vliet, P, Walker, M, Whiteley, W, (2022). Using the Barthel Index and modified Rankin Scale as Outcome Measures for Stroke Rehabilitation Trials; A Comparison of Minimum Sample Size Requirements Journal Of Stroke & Cerebrovascular Diseases 31, 106229
Underpowered trials risk inaccurate results. Recruitment to stroke rehabilitation randomised controlled trials (RCTs) is often a challenge. Statistical simulations offer an important opportunity to explore the adequacy of sample sizes in the context of specific outcome measures. We aimed to examine and compare the adequacy of stroke rehabilitation RCT sample sizes using the Barthel Index (BI) or modified Rankin Scale (mRS) as primary outcomes.We conducted computer simulations using typical experimental event rates (EER) and control event rates (CER) based on individual participant data (IPD) from stroke rehabilitation RCTs. Event rates are the proportion of participants who experienced clinically relevant improvements in the RCT experimental and control groups. We examined minimum sample size requirements and estimated the number of participants required to achieve a number needed to treat within clinically acceptable boundaries for the BI and mRS.We secured 2350 IPD (18 RCTs). For a 90% chance of statistical accuracy on the BI a rehabilitation RCT would require 273 participants per randomised group. Accurate interpretation of effect sizes would require 1000s of participants per group. Simulations for the mRS were not possible as a clinically relevant improvement was not detected when using this outcome measure.Stroke rehabilitation RCTs with large sample sizes are required for accurate interpretation of effect sizes based on the BI. The mRS lacked sensitivity to detect change and thus may be unsuitable as a primary outcome in stroke rehabilitation trials.Copyright © 2021 Elsevier Inc. All rights reserved.
JTD Keywords:  , barthel index, design, increasing value, modified rankin scale, randomised controlled trials, recruitment, reducing waste, reliability, sample size calculations, simulations, stroke rehabilitation, Adult, Article, Barthel index, Calculation, Computer simulation, Controlled study, Effect size, Female, Human, Human experiment, Major clinical study, Male, Modified rankin scale, Numbers needed to treat, Outcome assessment, Randomised controlled trials, Randomized controlled trial, Randomized controlled-trials, Rankin scale, Recruitment, Rehabilitation, Sample size, Sample size calculations, Simulations, Stroke rehabilitation
Beltrán G, Navajas D, García-Aznar JM, (2022). Mechanical modeling of lung alveoli: From macroscopic behaviour to cell mechano-sensing at microscopic level Journal Of The Mechanical Behavior Of Biomedical Materials 126, 105043
The mechanical signals sensed by the alveolar cells through the changes in the local matrix stiffness of the extracellular matrix (ECM) are determinant for regulating cellular functions. Therefore, the study of the mechanical response of lung tissue becomes a fundamental aspect in order to further understand the mechanosensing signals perceived by the cells in the alveoli. This study is focused on the development of a finite element (FE) model of a decellularized rat lung tissue strip, which reproduces accurately the mechanical behaviour observed in the experiments by means of a tensile test. For simulating the complex structure of the lung parenchyma, which consists of a heterogeneous and non-uniform network of thin-walled alveoli, a 3D model based on a Voronoi tessellation is developed. This Voronoi-based model is considered very suitable for recreating the geometry of cellular materials with randomly distributed polygons like in the lung tissue. The material model used in the mechanical simulations of the lung tissue was characterized experimentally by means of AFM tests in order to evaluate the lung tissue stiffness on the micro scale. Thus, in this study, the micro (AFM test) and the macro scale (tensile test) mechanical behaviour are linked through the mechanical simulation with the 3D FE model based on Voronoi tessellation. Finally, a micro-mechanical FE-based model is generated from the Voronoi diagram for studying the stiffness sensed by the alveolar cells in function of two independent factors: the stretch level of the lung tissue and the geometrical position of the cells on the extracellular matrix (ECM), distinguishing between pneumocyte type I and type II. We conclude that the position of the cells within the alveolus has a great influence on the local stiffness perceived by the cells. Alveolar cells located at the corners of the alveolus, mainly type II pneumocytes, perceive a much higher stiffness than those located in the flat areas of the alveoli, which correspond to type I pneumocytes. However, the high stiffness, due to the macroscopic lung tissue stretch, affects both cells in a very similar form, thus no significant differences between them have been observed. © 2021 The Authors
JTD Keywords: rat, scaffolds, stiffness, Afm, Animal cell, Animal experiment, Animal model, Animal tissue, Article, Biological organs, Cell function, Cells, Computational geometry, Cytology, Extracellular matrices, Extracellular matrix, Extracellular-matrix, Geometry, High stiffness, Human, Lung alveolus cell type 1, Lung alveolus cell type 2, Lung parenchyma, Lung tissue, Male, Mechanical behavior, Mechanical modeling, Mechanical simulations, Mechanosensing, Model-based opc, Nonhuman, Physical model, Rat, Rigidity, Stiffness, Stiffness matrix, Tensile testing, Thin walled structures, Three dimensional finite element analysis, Tissue, Type ii, Voronoi tessellations
Martí, Didac, Alemán, Carlos, Ainsley, Jon, Ahumada, Oscar, Torras, Juan, (2022). IgG1-b12–HIV-gp120 Interface in Solution: A Computational Study Journal Of Chemical Information And Modeling 62, 359-371
The use of broadly neutralizing antibodies against human immunodeficiency virus type 1 (HIV-1) has been shown to be a promising therapeutic modality in the prevention of HIV infection. Understanding the b12-gp120 binding mechanism under physiological conditions may assist the development of more broadly effective antibodies. In this work, the main conformations and interactions between the receptor-binding domain (RBD) of spike glycoprotein gp120 of HIV-1 and the IgG1-b12 mAb are studied. Accelerated molecular dynamics (aMD) and ab initio hybrid molecular dynamics have been combined to determine the most persistent interactions between the most populated conformations of the antibody-antigen complex under physiological conditions. The results show the most persistent receptor-binding mapping in the conformations of the antibody-antigen interface in solution. The binding-free-energy decomposition reveals a small enhancement in the contribution played by the CDR-H3 region to the b12-gp120 interface compared to the crystal structure.
JTD Keywords: antibody, complex, functionals, gp120 envelope glycoprotein, hiv, immunodeficiency-virus, noncovalent interactions, simulations, software integration, Ab initio, Accelerated molecular dynamics, Accelerated molecular-dynamics, Antibodies, Antigens, Binding energy, Binding mechanisms, Computational studies, Crystal structure, Diseases, Free energy, Hiv infection, Human immunodeficiency virus, Molecular dynamics, Neutralizing antibodies, Physiological condition, Physiology, Receptor-binding domains, Therapeutic modality, Viruses
Páscoa dos Santos F, Verschure PFMJ, (2022). Excitatory-Inhibitory Homeostasis and Diaschisis: Tying the Local and Global Scales in the Post-stroke Cortex Frontiers In Systems Neuroscience 15, 806544
Maintaining a balance between excitatory and inhibitory activity is an essential feature of neural networks of the neocortex. In the face of perturbations in the levels of excitation to cortical neurons, synapses adjust to maintain excitatory-inhibitory (EI) balance. In this review, we summarize research on this EI homeostasis in the neocortex, using stroke as our case study, and in particular the loss of excitation to distant cortical regions after focal lesions. Widespread changes following a localized lesion, a phenomenon known as diaschisis, are not only related to excitability, but also observed with respect to functional connectivity. Here, we highlight the main findings regarding the evolution of excitability and functional cortical networks during the process of post-stroke recovery, and how both are related to functional recovery. We show that cortical reorganization at a global scale can be explained from the perspective of EI homeostasis. Indeed, recovery of functional networks is paralleled by increases in excitability across the cortex. These adaptive changes likely result from plasticity mechanisms such as synaptic scaling and are linked to EI homeostasis, providing a possible target for future therapeutic strategies in the process of rehabilitation. In addition, we address the difficulty of simultaneously studying these multiscale processes by presenting recent advances in large-scale modeling of the human cortex in the contexts of stroke and EI homeostasis, suggesting computational modeling as a powerful tool to tie the meso- and macro-scale processes of recovery in stroke patients. Copyright © 2022 Páscoa dos Santos and Verschure.
JTD Keywords: balanced excitation, canonical microcircuit, cerebral-cortex, cortical excitability, cortical reorganization, diaschisis, excitability, excitatory-inhibitory balance, functional networks, homeostatic plasticity, ischemic-stroke, neuronal avalanches, photothrombotic lesions, state functional connectivity, whole-brain models, Algorithm, Biological marker, Brain, Brain cell, Brain cortex, Brain function, Brain radiography, Cerebrovascular accident, Cortical reorganization, Diaschisis, Down regulation, Excitability, Excitatory-inhibitory balance, Fluorine magnetic resonance imaging, Functional networks, Homeostasis, Homeostatic plasticity, Human, Motor dysfunction, Neuromodulation, Plasticity, Pyramidal nerve cell, Review, Simulation, Stroke, Stroke patient, Theta-burst stimulation, Visual cortex
Palacios, LS, Scagliarini, A, Pagonabarraga, I, (2022). A lattice Boltzmann model for self-diffusiophoretic particles near and at liquid-liquid interfaces Journal Of Chemical Physics 156, 224105
We introduce a novel mesoscopic computational model based on a multiphase-multicomponent lattice Boltzmann method for the simulation of self-phoretic particles in the presence of liquid-liquid interfaces. Our model features fully resolved solvent hydrodynamics, and, thanks to its versatility, it can handle important aspects of the multiphysics of the problem, including particle wettability and differential solubility of the product in the two liquid phases. The method is extensively validated in simple numerical experiments, whose outcome is theoretically predictable, and then applied to the study of the behavior of active particles next to and trapped at interfaces. We show that their motion can be variously steered by tuning relevant control parameters, such as the phoretic mobilities, the contact angle, and the product solubility. Published under an exclusive license by AIP Publishing.
JTD Keywords: Colloids, Equation, Gas, Numerical simulations, Particulate suspensions
Rosales-Rojas, R, Zuniga-Bustos, M, Salas-Sepulveda, F, Galaz-Araya, C, Zamora, RA, Poblete, H, (2022). Self-Organization Dynamics of Collagen-like Peptides Crosslinking Is Driven by Rose-Bengal-Mediated Electrostatic Bridges Pharmaceutics 14, 1148
The present work focuses on the computational study of the structural micro-organization of hydrogels based on collagen-like peptides (CLPs) in complex with Rose Bengal (RB). In previous studies, these hydrogels computationally and experimentally demonstrated that when RB was activated by green light, it could generate forms of stable crosslinked structures capable of regenerating biological tissues such as the skin and cornea. Here, we focus on the structural and atomic interactions of two collagen-like peptides (collagen-like peptide I (CLPI), and collagen-like peptide II, (CLPII)) in the presence and absence of RB, highlighting the acquired three-dimensional organization and going deep into the stabilization effect caused by the dye. Our results suggest that the dye could generate a ternary ground-state complex between collagen-like peptide fibers, specifically with positively charged amino acids (Lys in CLPI and Arg in CLPII), thus stabilizing ordered three-dimensional structures. The discoveries generated in this study provide the structural and atomic bases for the subsequent rational development of new synthetic peptides with improved characteristics for applications in the regeneration of biological tissues during photochemical tissue bonding therapies.
JTD Keywords: collagen-like peptide, crosslinking, molecular dynamics, qm/mm simulations, rose bengal, Anastomosis, Collagen-like peptide, Crosslinking, Green light, Mm simulations, Molecular dynamics, Molecular-dynamics, Photochemical tissue bonding therapies, Qm, Rose bengal
Martí D, Torras J, Bertran O, Turon P, Alemán C, (2021). Temperature effect on the SARS-CoV-2: A molecular dynamics study of the spike homotrimeric glycoprotein Computational And Structural Biotechnology Journal 19, 1848-1862
Rapid spread of SARS-CoV-2 virus have boosted the need of knowledge about inactivation mechanisms to minimize the impact of COVID-19 pandemic. Recent studies have shown that SARS-CoV-2 virus can be disabled by heating, the exposure time for total inactivation depending on the reached temperature (e.g. more than 45 min at 329 K or less than 5 min at 373 K. In spite of recent crystallographic structures, little is known about the molecular changes induced by the temperature. Here, we unravel the molecular basis of the effect of the temperature over the SARS-CoV-2 spike glycoprotein, which is a homotrimer with three identical monomers, by executing atomistic molecular dynamics (MD) simulations at 298, 310, 324, 338, 358 and 373 K. Furthermore, both the closed down and open up conformational states, which affect the accessibility of receptor binding domain, have been considered. Our results suggest that the spike homotrimer undergoes drastic changes in the topology of the hydrogen bonding interactions and important changes on the secondary structure of the receptor binding domain (RBD), while electrostatic interactions (i.e. salt bridges) are mainly preserved. The proposed inactivation mechanism has important implications for engineering new approaches to fight the SARS-CoV-2 coronavirus, as for example, cleaving or reorganizing the hydrogen bonds through chaotropic agents or nanoparticles with local surface resonant plasmon effect.
JTD Keywords: atomistic simulations, coronaviruses, denaturation, homotrimeric protein, inactivation, proteins, receptor binding domain, salt bridges, simulation, thermal inactivation, virus spike, Atomistic simulations, Homotrimeric protein, Receptor binding domain, Secondary-structure, Thermal inactivation, Virus spike
Cuervo, A., Dans, P. D., Carrascosa, J. L., Orozco, M., Gomila, G., Fumagalli, L., (2014). Direct measurement of the dielectric polarization properties of DNA Proceedings of the National Academy of Sciences of the United States of America 111, (35), E3624-E3630
The electric polarizability of DNA, represented by the dielectric constant, is a key intrinsic property that modulates DNA interaction with effector proteins. Surprisingly, it has so far remained unknown owing to the lack of experimental tools able to access it. Here, we experimentally resolved it by detecting the ultraweak polarization forces of DNA inside single T7 bacteriophages particles using electrostatic force microscopy. In contrast to the common assumption of low-polarizable behavior like proteins (εr ~ 2–4), we found that the DNA dielectric constant is ~ 8, considerably higher than the value of ~ 3 found for capsid proteins. State-of-the-art molecular dynamic simulations confirm the experimental findings, which result in sensibly decreased DNA interaction free energy than normally predicted by Poisson–Boltzmann methods. Our findings reveal a property at the basis of DNA structure and functions that is needed for realistic theoretical descriptions, and illustrate the synergetic power of scanning probe microscopy and theoretical computation techniques.
JTD Keywords: Atomic force microscopy, Atomistic simulations, DNA packaging, DNA-ligand binding, Poisson-Boltzmann equation, capsid protein, DNA, double stranded DNA, amino acid composition, article, atomic force microscopy, bacteriophage, bacteriophage T7, dielectric constant, dipole, DNA binding, DNA packaging, DNA structure, electron microscopy, ligand binding, nonhuman, polarization, priority journal, protein analysis, protein DNA interaction, scanning probe microscopy, static electricity, virion, virus capsid, virus particle, atomic force microscopy, atomistic simulations, DNA packaging, DNA-ligand binding, Poisson-Boltzmann equation, Bacteriophage T7, Capsid, Cations, Dielectric Spectroscopy, DNA, DNA, Viral, DNA-Binding Proteins, Electrochemical Techniques, Ligands, Microscopy, Atomic Force, Models, Chemical, Nuclear Proteins
Ziyatdinov, A., Diaz, E. Fernández, Chaudry, A., Marco, S., Persaud, K., Perera, A., (2013). A software tool for large-scale synthetic experiments based on polymeric sensor arrays Sensors and Actuators B: Chemical 177, 596-604
This manuscript introduces a software tool that allows for the design of synthetic experiments in machine olfaction. The proposed software package includes both, a virtual sensor array that reproduces the diversity and response of a polymer array and tools for data generation. The synthetic array of sensors allows for the generation of chemosensor data with a variety of characteristics: unlimited number of sensors, support of multicomponent gas mixtures and full parametric control of the noise in the system. The artificial sensor array is inspired from a reference database of seventeen polymeric sensors with concentration profiles for three analytes. The main features in the sensor data, like sensitivity, diversity, drift and sensor noise, are captured by a set of models under simplified assumptions. The generator of sensor signals can be used in applications related to test and benchmarking of signal processing methods, neuromorphic simulations in machine olfaction and educational tools. The software is implemented in R language and can be freely accessed.
JTD Keywords: Gas Sensor Array, Conducting Polymers, Electronic Nose, Sensor Simulation, Synthetic Dataset, Benchmark, Educational Tool
Valle-Delgado, J. J., Liepina, I., Lapidus, D., Sabaté, R., Ventura, S., Samitier, J., Fernàndez-Busquets, X., (2012). Self-assembly of human amylin-derived peptides studied by atomic force microscopy and single molecule force spectroscopy Soft Matter 8, (4), 1234-1242
The self-assembly of peptides and proteins into amyloid fibrils of nanometric thickness and up to several micrometres in length, a phenomenon widely observed in biological systems, has recently aroused a growing interest in nanotechnology and nanomedicine. Here we have applied atomic force microscopy and single molecule force spectroscopy to study the amyloidogenesis of a peptide derived from human amylin and of its reverse sequence. The spontaneous formation of protofibrils and their orientation along well-defined directions on graphite and DMSO-coated graphite substrates make the studied peptides interesting candidates for nanotechnological applications. The measured binding forces between peptides correlate with the number of hydrogen bonds between individual peptides inside the fibril structure according to molecular dynamics simulations.
JTD Keywords: Amyloid fibril, Amyloidogenesis, Binding forces, Fibril structure, Graphite substrate, Molecular dynamics simulations, Nanometrics, Protofibrils, Single molecule force spectroscopy, Spontaneous formation, Atomic force microscopy, Atomic spectroscopy, Graphite, Hydrogen bonds, Medical nanotechnology, Molecular dynamics, Molecular physics, Self assembly, Thickness measurement, Peptides
Redondo-Morata, Lorena, Oncins, Gerard, Sanz, Fausto, (2012). Force spectroscopy reveals the effect of different ions in the nanomechanical behavior of phospholipid model membranes: The case of potassium cation Biophysical Journal , 102, (1), 66-74
How do metal cations affect the stability and structure of phospholipid bilayers? What role does ion binding play in the insertion of proteins and the overall mechanical stability of biological membranes? Investigators have used different theoretical and microscopic approaches to study the mechanical properties of lipid bilayers. Although they are crucial for such studies, molecular-dynamics simulations cannot yet span the complexity of biological membranes. In addition, there are still some experimental difficulties when it comes to testing the ion binding to lipid bilayers in an accurate way. Hence, there is a need to establish a new approach from the perspective of the nanometric scale, where most of the specific molecular phenomena take place. Atomic force microscopy has become an essential tool for examining the structure and behavior of lipid bilayers. In this work, we used force spectroscopy to quantitatively characterize nanomechanical resistance as a function of the electrolyte composition by means of a reliable molecular fingerprint that reveals itself as a repetitive jump in the approaching force curve. By systematically probing a set of bilayers of different composition immersed in electrolytes composed of a variety of monovalent and divalent metal cations, we were able to obtain a wealth of information showing that each ion makes an independent and important contribution to the gross mechanical resistance and its plastic properties. This work addresses the need to assess the effects of different ions on the structure of phospholipid membranes, and opens new avenues for characterizing the (nano)mechanical stability of membranes.
JTD Keywords: Molecular-dynamics simulation, Liquid expanded monolayers, Lipid-bilayers, Hofmeister series, Monovalent salt, Phosphatidylcholine, Microscopy, Binding, Surfaces, NaCl
Pomareda, Victor, Marco, Santiago, (2011). Chemical plume source localization with multiple mobile sensors using bayesian inference under background signals Olfaction and Electronic Nose: Proceedings of the 14th International Symposium on Olfaction and Electronic Nose AIP Conference Proceedings (ed. Perena Gouma, SUNY Stony Brook), AIP (New York City, USA) 1362, (1), 149-150
This work presents the estimation of a likelihood map for the location of a source of chemical plume using multiple mobile sensors and Bayesian Inference. Previously described methods use a single sensor and just binary detections (concentrations above or below a certain threshold). The main contribution of this work is to extend previous proposals to use concentration information while at the same time being robust against the presence of background signals. The algorithm has two parts. The first part, concerning Adaptive Background Estimation, uses robust statistics measurements to estimate the background level despite the intermittent presence of high concentrations due to plume statistics. The second part of the algorithm estimates likelihood functions for background and for condition plus plume. Then, the algorithm sequentially builds a likelihood probability map for the location of the source. The algorithm allows the use of multiple mobile sensors. The simulation results demonstrate that our algorithm estimates better the source location and is much more robust in the presence of false alarms.
JTD Keywords: Sensors, Inference mechanisms, Probability, Simulation
Garcia-Manyes, S., Redondo-Morata, L., Oncins, G., Sanz, F., (2010). Nanomechanics of lipid bilayers: Heads or tails? Journal of the American Chemical Society American Chemical Society 132, (37), 12874-12886
Understanding the effect of mechanical stress on membranes is of primary importance in biophysics. Here we use force spectroscopy AFM to quantitatively characterize the nanomechanical stability of supported lipid bilayers as a function of their chemical composition. The onset of plastic deformation reveals itself as a repetitive jump in the approaching force curve, which represents a molecular fingerprint for the bilayer mechanical stability. By systematically probing a set of chemically distinct supported lipid bilayers (SLBs), we first show that both the headgroup and tail have a decisive effect on their mechanical properties. While the mechanical stability of the probed SLBs linearly increases by 3.3 nN upon the introduction of each additional -CH2- in the chain, it exhibits a significant dependence on the phospholipid headgroup, ranging from 3 nN for DPPA to 66 nN for DPPG. Furthermore, we also quantify the reduction of the membrane mechanical stability as a function of the number of unsaturations and molecular branching in the chemical structure of the apolar tails. Finally, we demonstrate that, upon introduction of cholesterol and ergosterol, contrary to previous belief the mechanical stability of membranes not only increases linearly in the liquid phase (DLPC) but also for phospholipids present in the gel phase (DPPC). Our results are discussed in the framework of the continuum nucleation model. This work highlights the compelling effect of subtle variations in the chemical structure of phospholipid molecules on the membrane response when exposed to mechanical forces, a mechanism of common occurrence in nature.
JTD Keywords: Atomic-force microscopy, Molecular-dynamics simulation, Aqueous-electrolyte solutions, Supported planar membranes, Phospholipid-bilayers, Biological-membranes, Physical-properties, Fluid membranes, Model membranes, Chain-length
Fonollosa, J., Carmona, M., Santander, J., Fonseca, L., Moreno, M., Marco, S., (2009). Limits to the integration of filters and lenses on thermoelectric IR detectors by flip-chip techniques Sensors and Actuators A: Physical , 149, (1), 65-73
In the trend towards miniaturization, a detector module containing multiple IR sensor channels is being built and characterized. In its final form it contains thermopiles, narrow band filters and Fresnel lenses. An important feature of such module is the assembly by flip-chip of the IR filters on top of the thermopiles. The performance of the filter-thermopile ensemble has been assessed by physical simulation and experiments and it has been optimized by the use of an empirically validated model. It has been found that integration of filters (or lenses) too close to the IR detector may lead to degraded performance due to thermal coupling. The impact and extent of this degradation has been thoroughly explored, being the main parameter the distance between the IR sensor and the filter. To avoid such detrimental effects a possibility is to set the device in vacuum conditions, obtaining an improved output response and avoiding the influence of the filters. Another way is to increase the solder joint height. Beyond a certain height, the filter is considered to be isolated from the thermopile.
JTD Keywords: Assembly, Infrared sensor, Infrared filter, Fresnel lenses, FEM simulation, Optimization
Gavara, N., Roca-Cusachs, P., Sunyer, R., Farre, R., Navajas, D., (2008). Mapping cell-matrix stresses during stretch reveals inelastic reorganization of the cytoskeleton Biophysical Journal , 95, (1), 464-471
The mechanical properties of the living cell are intimately related to cell signaling biology through cytoskeletal tension. The tension borne by the cytoskeleton (CSK) is in part generated internally by the actomyosin machinery and externally by stretch. Here we studied how cytoskeletal tension is modified during stretch and the tensional changes undergone by the sites of cell-matrix interaction. To this end we developed a novel technique to map cell-matrix stresses during application of stretch. We found that cell-matrix stresses increased with imposition of stretch but dropped below baseline levels on stretch release. Inhibition of the actomyosin machinery resulted in a larger relative increase in CSK tension with stretch and in a smaller drop in tension after stretch release. Cell-matrix stress maps showed that the loci of cell adhesion initially bearing greater stress also exhibited larger drops in traction forces after stretch removal. Our results suggest that stretch partially disrupts the actin-myosin apparatus and the cytoskeletal structures that support the largest CSK tension. These findings indicate that cells use the mechanical energy injected by stretch to rapidly reorganize their structure and redistribute tension.
JTD Keywords: Cell Line, Computer Simulation, Cytoskeleton/ physiology, Elasticity, Epithelial Cells/ physiology, Extracellular Matrix/ physiology, Humans, Mechanotransduction, Cellular/ physiology, Models, Biological, Stress, Mechanical
Roca-Cusachs, P., Alcaraz, J., Sunyer, R., Samitier, J., Farre, R., Navajas, D., (2008). Micropatterning of single endothelial cell shape reveals a tight coupling between nuclear volume in G1 and proliferation Biophysical Journal , 94, (12), 4984-4995
Shape-dependent local differentials in cell proliferation are considered to be a major driving mechanism of structuring processes in vivo, such as embryogenesis, wound healing, and angiogenesis. However, the specific biophysical signaling by which changes in cell shape contribute to cell cycle regulation remains poorly understood. Here, we describe our study of the roles of nuclear volume and cytoskeletal mechanics in mediating shape control of proliferation in single endothelial cells. Micropatterned adhesive islands were used to independently control cell spreading and elongation. We show that, irrespective of elongation, nuclear volume and apparent chromatin decondensation of cells in G1 systematically increased with cell spreading and highly correlated with DNA synthesis (percent of cells in the S phase). In contrast, cell elongation dramatically affected the organization of the actin cytoskeleton, markedly reduced both cytoskeletal stiffness (measured dorsally with atomic force microscopy) and contractility (measured ventrally with traction microscopy), and increased mechanical anisotropy, without affecting either DNA synthesis or nuclear volume. Our results reveal that the nuclear volume in G1 is predictive of the proliferative status of single endothelial cells within a population, whereas cell stiffness and contractility are not. These findings show that the effects of cell mechanics in shape control of proliferation are far more complex than a linear or straightforward relationship. Our data are consistent with a mechanism by which spreading of cells in G1 partially enhances proliferation by inducing nuclear swelling and decreasing chromatin condensation, thereby rendering DNA more accessible to the replication machinery.
JTD Keywords: Cell Line, Cell Nucleus/ physiology, Cell Proliferation, Cell Size, Computer Simulation, Endothelial Cells/ cytology/ physiology, G1 Phase/ physiology, Humans, Mechanotransduction, Cellular/ physiology, Models, Biological, Statistics as Topic
Udina, S., Carmona, M., Carles, G., Santander, J., Fonseca, L., Marco, S., (2008). A micromachined thermoelectric sensor for natural gas analysis: Thermal model and experimental results Sensors and Actuators B: Chemical 134, (2), 551-558
Natural gas may show significant changes in its chemical composition depending on its origin. Typically, natural gas analysis is carried out using process gas chromatography. However, other methods based on the evaluation of physical properties have recently been reported. Thermal conductivity sensors are currently used in the analysis of binary mixtures of dissimilar gases. In contrast, natural gas is a complex mixture of mainly hydrocarbons, plus other residual gases as carbon dioxide and nitrogen. In this work, the response of a micromachined sensor integrating a heater and a thermopile is studied, regarding its potential use for natural gas analysis. A finite element thermal model of the device is described, and thermal operation simulations as well as a preliminary sensitivity analysis are reported. Experimental data has been collected and compared with simulated data, showing very good agreement. Results show that small variations in the gas mixture composition can be clearly detected. The sensor appears as a good candidate to be included in low-cost natural gas property analysis and quality control systems.
JTD Keywords: Natural gas, Thermopile, MEMS, Thermal conductivity, Modeling, FEM simulation