The collection of exposed plasma membrane proteins, collectively termed the surfaceome, is involved in multiple vital cellular processes, such as the communication of cells with their surroundings and the regulation of transport across the lipid bilayer. The surfaceome also plays key roles in the immune system by recognizing and presenting antigens, with its possible malfunctioning linked to disease. Surface proteins have long been explored as potential cell markers, disease biomarkers, and therapeutic drug targets. Despite its importance, a detailed study of the surfaceome continues to pose major challenges for mass spectrometry-driven proteomics due to the inherent biophysical characteristics of surface proteins. Their inefficient extraction from hydrophobic membranes to an aqueous medium and their lower abundance compared to intracellular proteins hamper the analysis of surface proteins, which are therefore usually underrepresented in proteomic datasets. To tackle such problems, several innovative analytical methodologies have been developed. This review aims at providing an extensive overview of the different methods for surfaceome analysis, with respective considerations for downstream mass spectrometry-based proteomics.

中文翻译：

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质谱和细胞表面组

暴露的质膜蛋白的集合，统称为表面组，涉及多个重要的细胞过程，例如细胞与其周围环境的通讯以及跨脂质双层的转运调节。表面组还通过识别和呈递抗原在免疫系统中发挥关键作用，其可能的故障与疾病有关。长期以来，表面蛋白一直被探索为潜在的细胞标志物、疾病生物标志物和治疗药物靶点。尽管其重要性，但由于表面蛋白固有的生物物理特性，对表面组的详细研究继续对质谱驱动的蛋白质组学提出重大挑战。与细胞内蛋白质相比，它们从疏水膜到水性介质的低效提取以及较低的丰度阻碍了表面蛋白质的分析，因此在蛋白质组数据集中通常代表性不足。为了解决这些问题，已经开发了几种创新的分析方法。本综述旨在提供对表面组分析不同方法的广泛概述，并分别考虑基于下游质谱的蛋白质组学。