Tahir Mukarram A, Van Lehn Reid C, Choi S H, Alexander-Katz Alfredo
Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Biochim Biophys Acta. 2016 Jun;1858(6):1207-15. doi: 10.1016/j.bbamem.2016.01.026. Epub 2016 Jan 30.
The stochastic protrusion of hydrophobic lipid tails into solution, a subclass of hydrophobic membrane defects, has recently been shown to be a critical step in a number of biological processes like membrane fusion. Understanding the factors that govern the appearance of lipid tail protrusions is critical for identifying membrane features that affect the rate of fusion or other processes that depend on contact with solvent-exposed lipid tails. In this work, we utilize atomistic molecular dynamics simulations to characterize the likelihood of tail protrusions in phosphotidylcholine lipid bilayers of varying composition, curvature, and hydration. We distinguish two protrusion modes corresponding to atoms near the end of the lipid tail or near the glycerol group. Through potential of mean force calculations, we demonstrate that the thermodynamic cost for inducing a protrusion depends on tail saturation but is insensitive to other bilayer structural properties or hydration above a threshold value. Similarly, highly curved vesicles or micelles increase both the overall frequency of lipid tail protrusions as well as the preference for splay protrusions, both of which play an important role in driving membrane fusion. In multi-component bilayers, however, the incidence of protrusion events does not clearly depend on the mismatch between tail length or tail saturation of the constituent lipids. Together, these results provide significant physical insight into how system components might affect the appearance of protrusions in biological membranes, and help explain the roles of composition or curvature-modifying proteins in membrane fusion.
疏水脂质尾部随机突入溶液中，这是疏水膜缺陷的一个子类，最近已被证明是膜融合等许多生物过程中的关键步骤。了解控制脂质尾部突出出现的因素对于识别影响融合速率或其他依赖于与暴露于溶剂中的脂质尾部接触的过程的膜特征至关重要。在这项工作中，我们利用原子分子动力学模拟来表征不同组成、曲率和水合作用的磷脂酰胆碱脂质双层中尾部突出的可能性。我们区分了两种与脂质尾部末端附近或甘油基团附近的原子相对应的突出模式。通过平均力势计算，我们证明诱导突出的热力学成本取决于尾部饱和度，但对高于阈值的其他双层结构性质或水合作用不敏感。同样，高度弯曲的囊泡或胶束会增加脂质尾部突出的总体频率以及对展开突出的偏好，这两者在驱动膜融合中都起着重要作用。然而，在多组分双层中，突出事件的发生率并不明显取决于组成脂质的尾部长度或尾部饱和度之间的不匹配。总之，这些结果为系统组件如何影响生物膜中突出的出现提供了重要的物理见解，并有助于解释组成或曲率修饰蛋白在膜融合中的作用。
