Quantification of Aminophospholipid Asymmetry in Supported Lipid Bilayers by Neutron Reflectometry

细胞膜以脂双层为基础，表现出复杂的组成和组织。在健康细胞中，脂质在双层的两个小叶之间的分布是不对称的：磷脂酰丝氨酸(PS)仅限于膜的内小叶，而外小叶主要由磷脂酰胆碱和鞘磷脂组成。脂类也是横向排列的，在几十纳米的长度尺度上是不均匀的。这些现象是如何产生的尚不清楚，因为通常用来模拟细胞膜的典型的高熔点、低熔点、胆固醇的磷脂酰胆碱混合物表现出具有微米大小的区域的宏观相分离。能够捕捉脂质组织的横向和横向方面的模型系统很少，因此，研究细胞膜中脂质组织的这两个方面是如何相互耦合的一直是困难的。我们开发了一个模型系统，可以同时捕获这两个功能。它是基于二氧化钛表面支撑的脂质双层(SLB)，它包含高熔点、低熔点、胆固醇的磷脂酰胆碱和PS的混合物，这种混合物分布不对称。目前工作的目标是用中子反射仪(NR)来定量这些不对称细胞膜模拟物中的脂质分布，以便进一步研究这些体系中的相行为和脂类扩散。

Cell membranes are based on lipid bilayers that exhibit complex composition and organization. In healthy cells, the distribution of lipids between the two leaflets of the bilayer is asymmetric: phosphatidyl serine (PS) is restricted to the inner leaflet of the membrane, while the outer leaflet is predominantly composed of phosphatidyl choline and sphingomyelin. Lipids are also organized laterally, with heterogeneities on the lengthscale of tens of nm. How these arise is not clear, because the canonical high-melting, low-melting, cholesterol mixtures of phosphatidylcholines commonly used to model cell membranes exhibit macroscopic phase separation with um-size domains. Model systems that can capture both the lateral and the transverse aspects of lipid organization are scarce, and for that reason, studying how the two aspects of lipid organization in cell membranes couple to each other has been difficult. We developed a model system that captures both these features. It is based on supported lipid bilayers (SLBs) on TiO2 that contain the high-melting, low-melting, cholesterol mixture of phosphatidyl cholines, and PS, that is distributed asymmetrically. The goal of the current work is to quantify lipid distribution in these asymmetric cell membrane mimics by neutron reflectometry (NR) so that further studies of phase behavior and lipid diffusion in these systems could be carried out.