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Local anesthetics induce interdigitation and thermotropic changes in dipalmitoylphosphatidylcholine bilayers
Chemistry and Physics of Lipids ( IF 3.4 ) Pub Date : 2017-12-21 , DOI: 10.1016/j.chemphyslip.2017.12.003
S. Thirupathi Reddy , Sandeep Shrivastava , Amitabha Chattopadhyay

The molecular mechanism underlying the action of local anesthetics is still elusive. Phenylethanol (PEtOH) is an ingredient of essential oils with a rose-like odor and has been used as a local anesthetic. In this work, we have explored the effect of PEtOH on thermotropic behavior and organization of dipalmitoylphosphatidylcholine (DPPC) membranes utilizing differential scanning calorimetry (DSC) and small angle X-ray scattering (SAXS). Our results indicate that the phase transition temperature of DPPC exhibited decrease with increasing PEtOH concentration. This is accompanied by hysteresis (difference in phase transition between the heating and cooling scans). We defined the threshold concentration of PEtOH as the concentration at which the difference in phase transition temperature between the heating and cooling thermograms is maximum. Interestingly, changes in enthalpy, entropy, and full width at half maximum displayed biphasic behavior beyond the threshold concentration of PEtOH. The biphasic change in thermodynamic parameters corresponding to phase transtition, coupled with hysteresis, is indicative of interdigitation in DPPC bilayers. We confirmed this proposition by SAXS measurements which show formation of the interdigitated phase in DPPC bilayers at and above the threshold concentration of PEtOH. To the best of our knowledge, these results constitute the first report describing the interdigitation of membrane bilayers induced by PEtOH. We further show that the formation of interdigitated phase in DPPC bilayers depends on PEtOH concentration and temperature. Our results could be useful in ongoing efforts to address the mechanism of action of local anesthetics in model and biological membranes.



中文翻译:

局麻药诱导二棕榈酰磷脂酰胆碱双层分子的互指化和热致变化

局麻药作用的分子机制仍然难以捉摸。苯乙醇(PEtOH)是具有玫瑰味的香精油成分,已被用作局部麻醉剂。在这项工作中,我们利用差示扫描量热法(DSC)和小角度X射线散射(SAXS)探索了PEtOH对热致行为和二棕榈酰磷脂酰胆碱(DPPC)膜组织的影响。我们的结果表明,随着PEtOH浓度的增加,DPPC的相变温度降低。这伴随着磁滞现象(加热和冷却扫描之间的相变差异)。我们将PEtOH的阈值浓度定义为加热和冷却热分析图之间的相变温度差异最大的浓度。有趣的是,焓,熵和半峰全宽的变化显示出超过PEtOH阈值浓度的双相行为。对应于相变的热力学参数的双相变化,再加上磁滞现象,表明了DPPC双层中的相互交叉。我们通过SAXS测量证实了这一命题,该测量表明在PEtOH的阈值浓度以上,DPPC双层中的叉指状相的形成。据我们所知,这些结果构成了描述PEtOH诱导的膜双层相互交叉的第一个报告。我们进一步表明,DPPC双层中叉指状相的形成取决于PEtOH的浓度和温度。

更新日期:2017-12-21
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