Adriano Alencar - Academia.edu (original) (raw)

Papers by Adriano Alencar

PLOS ONE, 2015

A cell mechanical stimulation equipment, based on cell substrate deformation, and a more sensitiv... more A cell mechanical stimulation equipment, based on cell substrate deformation, and a more sensitive method for measuring adhesion of cells were developed. A probe, precisely positioned close to the cell, was capable of a vertical localized mechanical stimulation with a temporal frequency of 207 Hz, and strain magnitude of 50%. This setup was characterized and used to probe the response of Human Umbilical Endothelial Vein Cells (HUVECs) in terms of calcium signaling. The intracellular calcium ion concentration was measured by the genetically encoded Cameleon biosensor, with the Transient Receptor Potential cation channel, subfamily M, member 7 (TRPM7) expression inhibited. As TRPM7 expression also regulates adhesion, a relatively simple method for measuring adhesion of cells was also developed, tested and used to study the effect of adhesion alone. Three adhesion conditions of HUVECs on polyacrylamide gel dishes were compared. In the first condition, the substrate is fully treated with Sulfo-SANPAH crosslinking and fibronectin. The other two conditions had increasingly reduced adhesion: partially treated (only coated with fibronectin, with no use of Sulfo-SANPAH, at 5% of the normal amount) and non-treated polyacrylamide gels. The cells showed adhesion and calcium response to the mechanical stimulation correlated to the degree of gel treatment: highest for fully treated gels and lowest for non-treated ones. TRPM7 inhibition by siRNA on HUVECs caused an increase in adhesion relative to control (no siRNA treatment) and non-targeting siRNA, but a decrease to 80% of calcium response relative to non-targeting siRNA which confirms the important role of TRPM7 in mechanotransduction despite the increase in adhesion.

Experimental and Toxicologic Pathology, 2015

This study assessed the effects of the diesel exhaust particles on ERK and JNK MAPKs activation, ... more This study assessed the effects of the diesel exhaust particles on ERK and JNK MAPKs activation, cell rheology (viscoelasticity), and cytotoxicity in bronchial epithelial airway cells (BEAS-2B). Crude DEP and DEP after extraction with hexane (DEP/HEX) were utilized. The partial reduction of some DEP/HEX organics increased the biodisponibility of many metallic elements. JNK and ERK were activated simultaneously by crude DEP with no alterations in viscoelasticity of the cells. Mitochondrial activity, however, revealed a decrease through the MTT assay. DEP/HEX treatment increased viscoelasticity and cytotoxicity (membrane damage), and also activated JNK. Our data suggest that the greater bioavailability of metals could be involved in JNK activation and, consequently, in the reduction of fiber coherence and increase in the viscoelasticity and cytotoxicity of BEAS cells. The adverse findings detected after exposure to crude DEP and to DEP/HEX reflect the toxic potential of diesel compounds. Considering the fact that the cells of the respiratory epithelium are the first line of defense between the body and the environment, our data contribute to a better understanding of the pathways leading to respiratory cell injury and provide evidence for the onset of or worsening of respiratory diseases caused by inorganic compounds present in DEP.

A68. TISSUE REMODELING IN THE LUNG, 2012

Physical review. E, Statistical, nonlinear, and soft matter physics, 2009

We present Monte Carlo simulations for a molecular motor system found in virtually all eukaryotic... more We present Monte Carlo simulations for a molecular motor system found in virtually all eukaryotic cells, the acto-myosin motor system, composed of a group of organic macromolecules. Cell motors were mapped to an Ising-like model, where the interaction field is transmitted through a tropomyosin polymer chain. The presence of Ca2+ induces tropomyosin to block or unblock binding sites of the myosin motor leading to its activation or deactivation. We used the Metropolis algorithm to find the transient and the equilibrium states of the acto-myosin system composed of solvent, actin, tropomyosin, troponin, Ca2+, and myosin-S1 at a given temperature, including the spatial configuration of tropomyosin on the actin filament surface. Our model describes the short- and long-range cooperativity during actin-myosin binding which emerges from the bending stiffness of the tropomyosin complex. We found all transition rates between the states only using the interaction energy of the constituents. The...

Physical review. E, Statistical, nonlinear, and soft matter physics, 2006

In the course of certain lung diseases, the surface properties and the amount of fluids coating t... more In the course of certain lung diseases, the surface properties and the amount of fluids coating the airways changes and liquid bridges may form in the small airways blocking the flow of air, impairing gas exchange. During inhalation, these liquid bridges may rupture due to mechanical instability and emit a discrete sound event called pulmonary crackle, which can be heard using a simple stethoscope. We hypothesize that this sound is a result of the acoustical release of energy that had been stored in the surface of liquid bridges prior to its rupture. We develop a lattice gas model capable of describing these phenomena. As a step toward modeling this process, we address a simpler but related problem, that of a liquid bridge between two planar surfaces. This problem has been analytically solved and we use this solution as a validation of the lattice gas model of the liquid bridge rupture. Specifically, we determine the surface free energy and critical stability conditions in a system ...

Journal of Applied Physiology, 2003

Lung and alveolar wall elastic and hysteretic behavior in rats: effects of in vivo elastase treat... more Lung and alveolar wall elastic and hysteretic behavior in rats: effects of in vivo elastase treatment. .-We investigated the relationship between the microscopic elastic and hysteretic behavior of the alveolar walls and the macroscopic mechanical properties of the whole lung in an in vivo elastase-treated rat model of emphysema. We measured the input impedance of isolated lungs at three levels of transpulmonary pressure (Ptp) and used a linear model to estimate the dynamic elastance and hysteresivity of the lungs. The elastance of the normal lungs increased steeply with Ptp, whereas this dependence diminished in the treated lungs. Hysteresivity decreased significantly with Ptp in the normal lungs, but this dependence disappeared in the treated lungs. To investigate the microscopic origins of these changes, the alveolar walls were immunofluorescently labeled in small tissue strips. By using a fluorescent microscope, the lengths and angular orientations of individual alveolar walls were followed during cyclic uniaxial stretching of the tissue strips. The microstrains (relative change in segment length) and changes in angle of the alveolar walls showed considerable heterogeneity, which was interpreted in terms of a network model. In the normal strips, the alveolar walls showed larger angular changes compared with the treated tissue, whereas the alveolar walls of the treated tissue tended to be more extensible. Hysteresis in the average angle change was also larger in the treated tissue than in the normal tissue. We conclude that the decreased Ptp dependence of elastance and the constant hysteresivity in the treated lungs are related to microstructural remodeling and network phenomena at the level of the alveolar walls. collagen; elastin; fluorescent imaging; remodeling; mechanics EMPHYSEMA IS THOUGHT TO RESULT from the combined effects of inflammation and an imbalance of protease and antiprotease activity in the lung . Collagen and elastin, the main load-bearing fibers in the parenchyma, undergo remodeling during emphysema, and the remodeled fiber network has altered mechanical properties . Additionally, the mechanical forces applied to the lung during normal breathing can contribute to progressive destruction of remodeled al-Address for reprint requests and other correspondence:

American Journal of Physiology - Lung Cellular and Molecular Physiology, 2003

Physical Review E, 1999

During slow inflation of lung lobes, we measure a sequence of short explosive transient sound wav... more During slow inflation of lung lobes, we measure a sequence of short explosive transient sound waves called ``crackles,'' each consisting of an initial spike followed by ringing. The crackle time series is irregular and intermittent, with the number of spikes of size s following a power law, n(s)~s-alpha, with alpha=2.77+/-0.05. We develop a model of crackle wave generation and propagation

Several mechanical properties of the airway smooth muscle depend on the regulation of structure a... more Several mechanical properties of the airway smooth muscle depend on the regulation of structure and air- way viscoelasticity. Therefore, modifications of viscoelasticity caused by exposure to polluted air or diseases such as asthma can potentially deteriorate these mechanical properties with consequences to individual health. Formaldehyde is a well known experimental proxy found in the polluted air among several volatile organic substances. In polluted air, vapor of formaldehyde is an irritant that can affect multiple living tissues even at low concentrations. Formaldehyde deteriorate the airway function inducing asthma symptoms and develops airway hyperresponsiveness. The mechanical effect of formaldehyde is to stiffen the tissue, but the mechanism behind of this effect is not clear. Thus, the aims of this study is to simulate the smooth muscle mechanics by a network with a variety of viscoelastic properties of its links. We speculate that diseases that cause inflam- mation of the ...

Physical Review E, 2003

We study an invasion percolation process on Cayley trees and find that the dynamics of perimeter ... more We study an invasion percolation process on Cayley trees and find that the dynamics of perimeter growth is strongly dependent on the nature of the invasion process, as well as on the underlying tree structure. We apply this process to model the inflation of the lung in the airway tree, where crackling sounds are generated when airways open. We define the perimeter as the interface between the closed and opened regions of the lung. In this context we find that the distribution of time intervals between consecutive openings is a power law with an exponent ␤Ϸ2. We generalize the binary structure of the lung to a Cayley tree with a coordination number Z between 2 and 4. For Zϭ4, ␤ remains close to 2, while for a chain, Zϭ2 and ␤ϭ1, exactly. We also find a mean field solution of the model.

A65. GENE EXPRESSION, PHENOTYPE, AND FUNCTION IN AIRWAY SMOOTH MUSCLE: NEW INSIGHTS, 2010

We analyze the problem of fluid transport through a model system relevant to the inflation of a m... more We analyze the problem of fluid transport through a model system relevant to the inflation of a mammalian lung, an asymmetric bifurcating structure containing random blockages that can be removed by the pressure of the fluid itself. We obtain a comprehensive description of the fluid flow in terms of the topology of the structure and the mechanisms which open the blockages. We show that when calculating averaged flow properties of the fluid, the tree structure can be partitioned into a linear superposition of one-dimensional chains. In particular, we relate the pressure-volume P-V relationship of the fluid to the distribution ⌸(n) of the generation number n of the tree's terminal branches, a structural property. We invert this relation to obtain a statistical description of the underlying branching structure of the lung, by analyzing experimental pressure-volume data from dog lungs. The ⌸(n) extracted from the experimental P-V data agrees well with available data on lung branching structure. Our general results are applicable to any physical system involving transport in bifurcating structures with removable closures.

Applied Physics Letters, 1991

The time evolution of the minority electron velocity and temperature in p-GaAs towards the steady... more The time evolution of the minority electron velocity and temperature in p-GaAs towards the steady state is calculated for high-electric fields and doping concentrations of 1.5 x 10" and 1.5 X lOI* cm -'. It is shown that the velocity overshoot is less pronounced for high doping concentration. The electron-hole interaction reduces the overshoot effect, which indicates its role in the high-field transport transient of minority carriers in p-GaAs.

Physical Review Letters, 2005

We study the distribution n D of airway diameters D as a function of generation N in asymmetric a... more We study the distribution n D of airway diameters D as a function of generation N in asymmetric airway trees of mammalian lungs. We find that the airway bifurcations are self-similar in four species studied. Specifically, the ratios of diameters of the major and minor daughters to their parent are constants independent of N until a cutoff diameter is reached. We derive closed form expressions for N D and examine the flow resistance of the tree based on an asymmetric flow division model. Our findings suggest that the observed diameter heterogeneity is consistent with an underlying regular branching asymmetry.

Physical Review Letters, 2006

We report on a model of a prestressed nonlinear semiflexible polymer chain that links thermally d... more We report on a model of a prestressed nonlinear semiflexible polymer chain that links thermally driven dynamics to the creep behavior of living cells. Numerical simulations show that the chain's creep follows a power law with an exponent that decreases with increasing prestress. This is related to the propagation of free energy through the chain in response to stretching, where the propagation speed is regulated by the prestress via the chain's nonlinear elasticity. These results indicate that the main aspects of cell rheology are consistent with the dynamics of single polymer chains under tension.

Physical Review E - Statistical, Nonlinear, and Soft Matter Physics, 2008

Rheological properties of adherent cells are essential for their physiological functions, and mic... more Rheological properties of adherent cells are essential for their physiological functions, and microrheological measurements on living cells have shown that their viscoelastic responses follow a weak power law over a wide range of time scales. This power law is also influenced by mechanical prestress borne by the cytoskeleton, suggesting that cytoskeletal prestress determines the cell's viscoelasticity, but the biophysical origins of this behavior are largely unknown. We have recently developed a stochastic two-dimensional model of an elastically joined chain that links the power-law rheology to the prestress. Here we use a similar approach to study the creep response of a prestressed three-dimensional elastically jointed chain as a viscoelastic model of semiflexible polymers that comprise the prestressed cytoskeletal lattice. Using a Monte Carlo based algorithm, we show that numerical simulations of the chain's creep behavior closely correspond to the behavior observed experimentally in living cells. The power-law creep behavior results from a finite-speed propagation of free energy from the chain's end points toward the center of the chain in response to an externally applied stretching force. The property that links the power law to the prestress is the chain's stiffening with increasing prestress, which originates from entropic and enthalpic contributions. These results indicate that the essential features of cellular rheology can be explained by the viscoelastic behaviors of individual semiflexible polymers of the cytoskeleton.

Biorheology, 2012

One drawback of in vitro cell culturing is the dedifferentiation process that cells experience. S... more One drawback of in vitro cell culturing is the dedifferentiation process that cells experience. Smooth muscle cells (SMC) also change molecularly and morphologically with long term culture. The main objective of this study was to evaluate if culture passages interfere in vascular SMC mechanical behavior. SMC were obtained from five different porcine arterial beds. Optical magnetic twisting cytometry (OMTC) was used to characterize mechanically vascular SMC from different cultures in distinct passages and confocal microscopy/western blotting, to evaluate cytoskeleton and extracellular matrix proteins. We found that vascular SMC rigidity or viscoelastic complex modulus (G) decreases with progression of passages. A statistically significant negative correlation between G and passage was found in four of our five cultures studied. Phalloidin-stained SMC from higher passages exhibited lower mean signal intensity per cell (confocal microscopy) and quantitative western blotting analysis showed a decrease in collagen I content throughout passages. We concluded that vascular SMC progressively lose their stiffness with serial culture passaging. Thus, limiting the number of passages is essential for any experiment measuring viscoelastic properties of SMC in culture.

Physica A: Statistical Mechanics and its Applications, 2013

Snoring is extremely common in the general population and when irregular may indicate the presenc... more Snoring is extremely common in the general population and when irregular may indicate the presence of obstructive sleep apnea. We analyze the overnight sequence of wave packets -the snore sound -recorded during full polysomnography in patients referred to the sleep laboratory due to suspected obstructive sleep apnea. We hypothesize that irregular snore, with duration in the range between 10 and 100 seconds, correlates with respiratory obstructive events. We find that the number of irregular snores -easily accessible, and quantified by what we call the snore time interval index (STII) -is in good agreement with the well-known apnea-hypopnea index, which expresses the severity of obstructive sleep apnea and is extracted only from