stretch channels

We use mesoscopic lattice-Boltzmann/molecular dynamics simulations to study the stretching behavior of a single tethered polymer in micro- and nanochannels. In particular, we are interested in the connection between fluid flow properties and the force on the polymer chain. An analytical expression for the stretching force is proposed, which linearly depends on the number of monomers and the boundary shear rate. In agreement with theory, the numerical findings reveal that the influence of hydrodynamic interactions can be ignored, which is also supported by results of additional Langevin dynamics simulations...

The present study was carried out to determine whether the mechanically activated cation channel Piezo1 protein plays a role as a signaling pathway which causes the apoptosis of human chondrocytes. The chondrocytes were isolated, cultured, and then subjected to mechanical stretch force for 0, 2, 12, 24 and 48 h, respectively. The expression levels of Piezo1 and the apoptosis-related protein caspase-12 were assessed by reverse transcription-quantitative polymerase chain reaction, as well as the apoptosis-related genes, B cell lymphoma/leukemia-2 (Bcl-2), Bcl-associated X protein (Bax) and Bcl-2-associated death promoter (BAD)...

Mechanosensitivity is a fundamental physiological capacity, which pertains to all life forms. Progress has been made with regard to understanding mechanosensitivity in bacteria, flies, and worms. In vertebrates, however, the molecular identity of mechanotransducers in somatic and neuronal cells has only started to appear. The Piezo family of mechanogated ion channels marks a pivotal milestone in understanding mechanosensitivity. Piezo1 and Piezo2 have now been shown to participate in a number of processes, ranging from arterial modeling to sensing muscle stretch...

Hindlimb skeletal muscle stretch (i.e., selective activation of the muscle mechanoreflex) in decerebrate rats evokes reflex increases in blood pressure and sympathetic nerve activity. Bradykinin has been found to sensitize mechano-gated channels through a bradykinin B2 receptor-dependent mechanism. Moreover, bradykinin B2 receptor expression on sensory neurons is increased following chronic femoral artery ligation in the rat (a model of simulated peripheral artery disease). We tested the hypothesis that, in decerebrate, unanesthetized rats, the injection of bradykinin into the arterial supply of a hindlimb would acutely augment (i...

The TREK-2 (KCNK10) K2P potassium channel can be regulated by variety of polymodal stimuli including pressure. In a recent study, we demonstrated that this mechanosensitive K(+) channel responds to changes in membrane tension by undergoing a major structural change from its 'down' state to the more expanded 'up' state conformation. These changes are mostly restricted to the lower part of the protein within the bilayer, but are allosterically coupled to the primary gating mechanism located within the selectivity filter...

In this work, we have investigated nonadiabatic dynamics in the vicinity of conical intersections for predissociation reactions of partially deuterated thioanisole molecules: C6H5S-CH2D and C6H5S-CHD2. Each isotopomer has two distinct rotational conformers according to the geometrical position of D or H of the methyl moiety with respect to the molecular plane for C6H5S-CH2D or C6H5S-CHD2, respectively, as spectroscopically characterized in our earlier report [J. Lee, S.-Y. Kim and S. K. Kim, J. Phys. Chem. A, 2014, 118, 1850]...

The Piezo1 protein ion channel is a novel mechanical stretch-activated ion channel (SAC) closely related to mechanical signals. Mechanotransduction plays a crucial role in organ development and homeostasis. Previous studies identified Piezo1 and demonstrated that it is distinct from other ion channels with well-established roles in lower organisms. Mechanical stretch-activated ion channels from other organisms are not conserved in mammals or do not act as mechanically activated channels in mammals. In the current study, we explored the role of the Piezo1 ion channel in human nucleus pulposus cell (NP cell) apoptosis through mechanical force-induced mitochondrial dysfunction and endoplasmic reticulum stress...

Cardiac contraction is controlled by a Ca(2+) signaling sequence that includes L-type Ca(2+) current-gated opening of Ca(2+) release channels (ryanodine receptors) in the sarcoplasmic reticulum (SR). Local Ca(2+) signaling in the atrium differs from that in the ventricle because atrial myocytes lack transverse tubules and have more abundant corbular SR. Myocardium is subjected to a variety of forces with each contraction, such as stretch, shear stress, and afterload, and adapts to those mechanical stresses...

The nonadiabatic dynamics of keto isocytosine in the gas phase has been investigated using the on-the-fly trajectory surface hopping method based on two electronic-structure methods: SA-CASSCF and ADC(2). The results estimate an excited-state lifetime of around 1000 fs at the SA-CASSCF level, while a much shorter lifetime of 250-350 fs is obtained at the ADC(2) level. Although three conical intersections (CIs) (Ethyl. I, Ethyl. II and C[double bond, length as m-dash]O stretching) are relevant to the nonadiabatic decay of keto isocytosine, their contributions to the nonadiabatic decay are highly dependent on the electronic-structure methods employed in the dynamics simulation...

The mechanism of brain edema is complex and still remains unclear. Our aim was to investigate the regional differences of cell volume and intracellular Ca(2+) concentration ([Ca(2+) ]i ) dynamics during hypotonic stress in male mouse hemi-brain slices. Brain slices were loaded with the fluorescence Ca(2+) indicator fura-2, and cell volume and [Ca(2+) ]i in the lateral cerebral cortex (LCC) and hippocampal CA1 (CA1) region were measured simultaneously during exposure to hypotonic stress using Ca(2+) insensitive (F360) and Ca(2+) sensitive fluorescence (F380), respectively...

Polymodal thermo- and mechanosensitive two-pore domain potassium (K2P) channels of the TREK subfamily generate 'leak' currents that regulate neuronal excitability, respond to lipids, temperature and mechanical stretch, and influence pain, temperature perception and anaesthetic responses. These dimeric voltage-gated ion channel (VGIC) superfamily members have a unique topology comprising two pore-forming regions per subunit. In contrast to other potassium channels, K2P channels use a selectivity filter 'C-type' gate as the principal gating site...

Extensional self-similar flows in a channel are explored numerically for arbitrary stretching-shrinking rates of the confining parallel walls. The present analysis embraces time integrations, and continuations of steady and periodic solutions unfolded in the parameter space. Previous studies focused on the analysis of branches of steady solutions for particular stretching-shrinking rates, although recent studies focused also on the dynamical aspects of the problems. We have adopted a dynamical systems perspective, analysing the instabilities and bifurcations the base state undergoes when increasing the Reynolds number...

Increased glomerular capillary pressure (glomerular hypertension) and increased glomerular filtration rate (glomerular hyperfiltration) have been proven to cause glomerulosclerosis in animal models and are likely to be operative in patients. Since podocytes cover the glomerular basement membrane, they are exposed to tensile stress due to circumferential wall tension and to fluid shear stress arising from filtrate flow through the narrow filtration slits and through Bowman's space. In vitro evidence documents that podocytes respond to tensile stress as well as to fluid shear stress...

The complement and neutrophil defense systems, as major components of innate immunity, are activated during inflammation and infection. For neutrophil migration to the inflamed region, we hypothesized that the complement activation product C5a induces significant changes in cellular morphology before chemotaxis. Exposure of human neutrophils to C5a, dose- and time-dependently resulted in a rapid C5a receptor-1 (C5aR1)-dependent shape-change, indicated by enhanced flow cytometric forward-scatter area values...

Mechanotransduction is the conversion of extracellular mechanical stimuli into intracellular biochemical signals, and plays an important role in heart responses to its own mechanical environment. Piezo1 as a distinct stretch-activated channel (SAC) in mammal involves in not only vascular remodeling during embryonic development but also arterial remodeling upon to hypertension at adult stage. In the present study, the expression of Piezo1 was up-regulated in failure heart induced by myocardial infarction (MI) by real-time PCR, Western blot and immunohistochemistry analysis...

Hydrogen-bonded network structures and preferential ion core in the protonated methanol-water mixed clusters, H+(methanol)n-(water)1 (n = 6 - 10), were explored by a combination of infrared spectroscopy and theoretical calculations. Infrared spectra of the OH stretch region of the clusters were measured at the two different temperature ranges by using Ar-tagging. Stable isomer structures of the clusters were searched by the multi-scale modeling approach and temperature dependent infrared spectra were simulated based on the statistical populations of the isomers...

Myogenic tone is an important feature of arterioles and resistance arteries, but the mechanisms responsible for this hallmark characteristic remain unclear. We utilized pharmacological inhibitors to compare the roles played by phospholipase C (PLC; 10 μM U73122), inositol 1,4,5 trisphosphate receptors (IP3R; 100 μM 2-Aminoethoxydiphenylborane, 2-APB), protein kinase C (PKC; 10μM Bisindolylmaleimide I), angiotensin II type 1 receptors (AT1R; 1μM losartan), Rho-kinase (10nM-30μM Y27632 or 300nM H1152), stretch-activated ion channels (10nM-1μM Gd(3+) or 5μM spider venom toxin GsMTx-4) and L-type voltage-gated Ca(2+) channels (0...

The role for mechanical stimulation in the control of cell fate has been previously proposed, suggesting that there may be a role of mechanical conditioning in directing mesenchymal stromal cells (MSCs) towards specific lineage for tissue engineering applications. Although previous studies have reported that calcium signalling is involved in regulating many cellular processes in many cell types, its role in managing cellular responses to tensile loading (mechanotransduction) of MSCs has not been fully elucidated...

Hollow organs (e.g. heart) experience pressure-induced mechanical wall stress sensed by molecular mechano-biosensors, including mechanosensitive ion channels, to translate into intracellular signaling. For direct mechanistic studies, stretch devices to apply defined extensions to cells adhered to elastomeric membranes have stimulated mechanotransduction research. However, most engineered systems only exploit unilateral cellular stretch. In addition, it is often taken for granted that stretch applied by hardware translates 1:1 to the cell membrane...

Microglia cells, resident immune cells of the brain, survey brain parenchyma by dynamically extending and retracting their processes. Cl(-) channels, activated in the cellular response to stretch/swelling, take part in several functions deeply connected with microglia physiology, including cell shape changes, proliferation, differentiation and migration. However, the molecular identity and functional properties of these Cl(-) channels are largely unknown. We investigated the properties of swelling-activated currents in microglial from acute hippocampal slices of Cx3cr1 (+/GFP) mice by whole-cell patch-clamp and imaging techniques...