Investigating Hydrophilic Pores in Model Lipid Bilayers Using Molecular Simulations: Correlating Bilayer Properties with Pore-Formation Thermodynamics.
Investigating Hydrophilic Pores in Model Lipid Bilayers Using Molecular Simulations: Correlating Bilayer Properties with Pore-Formation Thermodynamics.
复制标题
DOI：
10.1021/la504049q
复制
发表时间：
2015-06-23
期刊：
影响因子：
--
通讯作者：
Patel S
中科院分区：
文献类型：
--
作者：
Hu Y;Sinha SK;Patel S
细胞穿透肽和抗菌肽显示出显著的跨生理膜转运能力。沿着诸如电位诱导的膜结构扰动和表面张力效应的因素，实验在溶质转移到囊泡和细胞的过程中调用孔状膜构型。孔的引发和形成与非平凡的自由能成本相关，因此需要考虑与孔形成和伴随的自由能相关的因素。由于易位过程的长时间尺度相关的实验和建模的挑战，我们使用伞形采样的分子动力学模拟与脂质密度为基础的顺序参数调查膜孔形成自由能采用马提尼粗粒度模型。我们调查的结构和热力学特征的孔在18个脂质跨越一系列的头部基团，电荷状态，酰基链的长度和饱和度。我们探讨了三种不同脂质类的成孔屏障对每种脂质面积、脂质双层厚度、膜弯曲刚度的依赖性。在纯双层和肽移位的情况下的孔形成自由能与双层厚度显着耦合。较厚的双层需要更多的可逆功来产生孔。孔形成自由能在肽-脂质系统中相对于无肽脂质系统更高，这是由于在膜环境内维持带电亲水性溶质的溶剂化的罚分。
Cell-penetrating and antimicrobial peptides show remarkable ability to translocate across physiological membranes. Along with factors such as electric potential induced-perturbations of membrane structure and surface tension effects, experiments invoke pore-like membrane configurations during the solute transfer process into vesicles and cells. The initiation and formation of pores are associated with a non-trivial free energy cost, thus necessitating consideration of the factors associated with pore formation and attendant free energetics. Due to experimental and modeling challenges related to the long timescales of the translocation process, we use umbrella-sampling molecular dynamics simulations with a lipid-density based order parameter to investigate membrane pore-formation free energy employing Martini coarse-grained models. We investigate structure and thermodynamic features of the pore in 18 lipids spanning a range of head-groups, charge states, acyl chain lengths and saturation. We probe the dependence of pore-formation barriers on area per lipid, lipid bilayer thickness, membrane bending rigidities in three different lipid classes. The pore formation free energy in pure bilayers and peptide translocating scenarios are significantly coupled with bilayer thickness. Thicker bilayers require more reversible work to create pores. Pore formation free energy is higher in peptide-lipid systems relative to the peptide-free lipid systems due to penalties to maintain solvation of charged hydrophilic solutes within the membrane environment.