Molecular simulations and NMR reveal how lipid fluctuations affect membrane mechanics
Molecular simulations and NMR reveal how lipid fluctuations affect membrane mechanics
复制标题
分子模拟和核磁共振揭示脂质波动如何影响膜力学
DOI：
10.1016/j.bpj.2022.12.007
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发表时间：
2023
影响因子：
3.4
通讯作者：
Brown, Michael F.
中科院分区：
文献类型：
--
作者：
Doktorova, Milka;Khelashvili, George;Ashkar, Rana;Brown, Michael F.
脂质双层形成功能细胞膜的主要基质，并且它们的动力学是许多物理和生物过程的基础。在这里，我们表明，弹性膜性能和集体分子动力学（MD）相关的均方振幅（序参数）和松弛速率（相关时间）的脂酰基链运动。我们进行了全原子MD模拟的液晶双层，允许直接比较与碳-氢（CH）键弛豫与NMR光谱测量。以前的计算和理论方法都假设各向同性松弛，这会产生不准确的描述脂链动力学和不正确的数据解释。相反，新的框架包括一个固定的双层正常（导演轴）和限制的各向异性运动的CH键在雅阁与他们的分段参数，使强大的验证脂质力场。热激发CH键波动的模拟光谱密度表现出良好的定义自旋晶格（塞曼）松弛类似于那些在NMR测量。它们的频率特征可以用一个简单的幂律函数来拟合，这表明它们是类向列体的集体动力学。此外，计算的弛豫速率缩放的平方阶参数产生的双层弯曲的表观模量。我们的研究结果表明，从固态核磁共振研究中获得的值与胆固醇的膜弹性的中子自旋回波测量验证了一个很强的相关性。模拟揭示了一个关键的作用interleaflet耦合膜力学，从而提供了重要的见解内脂双层新兴的弹性性质的分子位点。
Lipid bilayers form the main matrix of functional cell membranes, and their dynamics underlie a host of physical and biological processes. Here we show that elastic membrane properties and collective molecular dynamics (MD) are related by the mean-square amplitudes (order parameters) and relaxation rates (correlation times) of lipid acyl chain motions. We performed all-atom MD simulations of liquid-crystalline bilayers that allow direct comparison with carbon-hydrogen (CH) bond relaxations measured with NMR spectroscopy. Previous computational and theoretical approaches have assumed isotropic relaxation, which yields inaccurate description of lipid chain dynamics and incorrect data interpretation. Instead, the new framework includes a fixed bilayer normal (director axis) and restricted anisotropic motion of the CH bonds in accord with their segmental order parameters, enabling robust validation of lipid force fields. Simulated spectral densities of thermally excited CH bond fluctuations exhibited well-defined spin-lattice (Zeeman) relaxations analogous to those in NMR measurements. Their frequency signature could be fit to a simple power-law function, indicative of nematic-like collective dynamics. Moreover, calculated relaxation rates scaled as the squared order parameters yielding an apparentmodulus for bilayer bending. Our results show a strong correlation withvalues obtained from solid-state NMR studies of bilayers without and with cholesterol as validated by neutron spin-echo measurements of membrane elasticity. The simulations uncover a critical role of interleaflet coupling in membrane mechanics and thus provide important insights into molecular sites of emerging elastic properties within lipid bilayers.