RESUMO
n-Aliphatic alcohols act as anesthetics only up to a certain chain length, beyond which its biological activity disappears. This is known as the 'cut-off' phenomenon. Although the most accepted explanation is based on action sites in membrane proteins, it is not well understood why alcohols alter their functions. The structural dependence of these protein receptors to lipid domains known as 'lipid rafts', suggests a new approach to tackle the puzzling phenomenon. In this work, by performing molecular dynamic simulations (MDS) to explore the lipid role, we provide relevant molecular details about the membrane-alcohol interaction at the cut-off point regime. Since the high variability of the cut-off points found on protein receptors in neurons may be a consequence of differences in the lipid composition surrounding such proteins, our results could have a clear-cut importance.
Assuntos
Álcoois , Anestésicos , Lipídeos , Microdomínios da Membrana , Simulação de Dinâmica MolecularRESUMO
Hundreds of substances possess anesthetic action. However, despite decades of research and tests, a golden rule is required to reconcile the diverse hypothesis behind anesthesia. What makes an anesthetic to be local or general in the first place? The specific targets on proteins, the solubility in lipids, the diffusivity, potency, action time? Here we show that there could be a new player equally or even more important to disentangle the riddle: the protonation rate. Indeed, such rate modulates the diffusion speed of anesthetics into lipid membranes; low protonation rates enhance the diffusion for local anesthetics while high ones reduce it. We show also that there is a pH and membrane phase dependence on the local anesthetic diffusion across multiple lipid bilayers. Based on our findings we incorporate a new clue that may advance our understanding of the anesthetic phenomenon.
Assuntos
Anestésicos/metabolismo , Lipídeos de Membrana/metabolismo , Membranas/metabolismo , Anestesia/métodos , Difusão , Concentração de Íons de Hidrogênio , SolubilidadeRESUMO
Molecular Dynamic Simulations are performed to evaluate the interaction of lidocaine, procaine and tetracaine with a lipid membrane. The main interest is to evaluate the structural changes produced by these local anesthetics in the bilayers. Penetration trajectories, interaction energies, entropy changes and an order parameter are calculated to quantify the destabilization of the lipid configurations. We show that such structural parameters give important information to understand how anesthetic agents influence the structure of plasma membranes. Graphic processing units (GPUs) are used in our simulations.
Assuntos
1,2-Dipalmitoilfosfatidilcolina/análogos & derivados , Anestésicos Locais/química , Lidocaína/química , Procaína/química , Tetracaína/química , 1,2-Dipalmitoilfosfatidilcolina/química , Entropia , Bicamadas Lipídicas/química , Conformação Molecular , Simulação de Dinâmica MolecularRESUMO
The mechanism of how a noble gas modifies the excitability of nerve cells and how such excitability can be recovered under hyperbaric pressure remains unclear. Here we present a calorimetric study where the melting point depression of pure lipid membranes induced by noble gases and its recovery with a hydrostatic pressure is addressed. A correlation is found between the electric polarizability (α) of these gases and their effect on the melting transition of the membranes. These results concur with other findings to support the idea that general anesthesia only depends on the ability of a certain atom or molecule to increase the general disorder of the membrane.
Assuntos
Lipídeos de Membrana/química , Gases Nobres/química , Calorimetria , Pressão Hidrostática , Lipossomos/química , Transição de FaseRESUMO
The study of motor properties of cells under appropriate physical-chemical conditions is a significant problem nowadays. The standard techniques presently used do not allow to evaluate neither large samples nor to control their thermodynamic conditions. In this work, we report a cell motility sensor based on an optical technique with a time-resolved correlation, adapted in a system able to study several samples simultaneously. Image correlation analysis is used to follow their temporal behavior. A wide variety of motile cells, such as archaea, bacteria, spermatozoa, and even contractile cells, can be studied using this technique. Here, we tested our technique with the study of sperm motility. In particular, both the sperm motility and its prevalence are studied under a temperature range from 0 to 37 °C. We found that incubation at 10 °C presents the lengthiest prevalence in motility and observed, for the first time, an interesting thermal reversibility behavior.
Assuntos
Dispositivos Ópticos , Motilidade dos Espermatozoides , Temperatura , Animais , Masculino , Camundongos , Fatores de TempoRESUMO
Acoustic gaps are normally observed in granular inhomogeneous structures made of composite materials. The modulation of the elastic properties in such media creates the coherent effects of scattering and interference that ultimately lead to frequency intervals where sound propagation is forbidden. Contrastingly, we report here an experimental observation of acoustic gaps in homogeneous media; specifically, in granular chains. The beads used in our study are magnetic. Therefore, instead of modulating the elastic properties of the chain, we modulate the magnetization (i.e., the contact forces). We also observe that the propagation speed of acoustic signals through the magnetic chains used in this study is at odds with the speed predicted by Hertz's law.