Understanding How Sterols Regulate Membrane Remodeling in Supported Lipid Bilayers

Understanding How Sterols Regulate Membrane Remodeling in Supported Lipid Bilayers
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DOI:
10.1021/acs.langmuir.7b03236
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发表时间:
2017-12-26
期刊:
影响因子:
3.9
通讯作者:
Cho, Nam-Joon
Cho, Nam-Joon
中科院分区:
化学2区
文献类型:
--
作者:
Kawakami, Lisa M.;Yoon, Bo Kyeong;Cho, Nam-Joon

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添加单链脂质两亲物,如抗微生物脂肪酸和甘油单酯到受限的二维磷脂双层中,可以触发三维膜形态的形成,作为调节压力的被动手段。迄今为止,已经使用纯磷脂组合物进行了相关的实验研究,并且将这种见解扩展到包括磷脂和甾醇的更复杂的生物相关的脂质组合物是必要的,因为甾醇是膜应力松弛的重要生物介质。本文采用石英晶体微平衡耗散(QCM-D)技术,研究了十二烷基硫酸钠(SDS)、月桂酸(LA)和甘油单月桂酸酯(GML)对磷脂和胆固醇混合物组成的支撑脂质双层(SLB)的膜重构作用。通过溶剂辅助的脂质双层方法制备SLB平台,以形成具有可调胆固醇分数(0-52摩尔%)的富含胆固醇的SLB。添加SDS或LA制造的SLB诱导小管形成,膜重塑的程度更大的SLB与高胆固醇馏分。与此形成鲜明对比的是,GML除了导致芽的形成,和膜重塑的程度较低的SLB与较高的胆固醇馏分。为了解释这些经验观察,我们讨论了胆固醇如何影响弹性(刚度)和粘性(应力松弛)的磷脂/胆固醇脂质双层的特性,以及如何膜易位特性的单链脂两亲物影响相应的膜形态反应。总的来说,我们的研究结果表明,单链脂质两亲物诱导高度特异性的膜形态反应在简化和复杂的模型膜,胆固醇可以促进或抑制膜重塑的各种分子机制。
The addition of single-chain lipid amphiphiles such as antimicrobial fatty acids and monoglycerides to confined, two-dimensional phospholipid bilayers can trigger the formation of three-dimensional membrane morphologies as a passive means to regulate stress. To date, relevant experimental studies have been conducted using pure phospholipid compositions, and extending such insights to more complex, biologically relevant lipid compositions that include phospholipids and sterols is warranted because sterols are important biological mediators of membrane stress relaxation. Herein, using the quartz crystal microbalancedissipation (QCM-D) technique, we investigated membrane remodeling behaviors triggered by the addition of sodium dodecyl sulfate (SDS), lauric acid (LA), and glycerol monolaurate (GML) to supported lipid bilayers (SLBs) composed of phospholipid and cholesterol mixtures. The SLB platforms were prepared by the solvent-assisted lipid bilayer method in order to form cholesterol-rich SLBs with tunable cholesterol fractions (0-52 mol %). The addition of SDS or LA to fabricated SLBs induced tubule formation, and the extent of membrane remodeling was greater in SLBs with higher cholesterol fractions. In marked contrast, GML addition led to bud formation, and the extent of membrane remodeling was lower in SLBs with higher cholesterol fractions. To explain these empirical observations, we discuss how cholesterol influences the elastic (stiffness) and viscous (stress relaxation) properties of phospholipid/cholesterol lipid bilayers as well as how the membrane translocation properties of single-chain lipid amphiphiles affect the corresponding membrane morphological responses. Collectively, our findings demonstrate that single-chain lipid amphiphiles induce highly specific membrane morphological responses across both simplified and complex model membranes, and cholesterol can promote or inhibit membrane remodeling by a variety of molecular mechanisms.