Department of Chemistry and Chemical Biology, Indiana University-Purdue University, Indianapolis 46202, USA.
Department of Chemistry and Chemical Biology, Indiana University-Purdue University, Indianapolis 46202, USA; Integrated Nanosystems Development Institute, IUPUI, Indianapolis, IN, USA.
Biochim Biophys Acta Biomembr. 2018 Oct;1860(10):2076-2093. doi: 10.1016/j.bbamem.2018.06.009. Epub 2018 Jun 21.
Most recent breakthroughs in understanding cell adhesion, cell migration, and cellular mechanosensitivity have been made possible by the development of engineered cell substrates of well-defined surface properties. Traditionally, these substrates mimic the extracellular matrix (ECM) environment by the use of ligand-functionalized polymeric gels of adjustable stiffness. However, such ECM mimetics are limited in their ability to replicate the rich dynamics found at cell-cell contacts. This review focuses on the application of cell surface mimetics, which are better suited for the analysis of cell adhesion, cell migration, and cellular mechanosensitivity across cell-cell interfaces. Functionalized supported lipid bilayer systems were first introduced as biomembrane-mimicking substrates to study processes of adhesion maturation during adhesion of functionalized vesicles (cell-free assay) and plated cells. However, while able to capture adhesion processes, the fluid lipid bilayer of such a relatively simple planar model membrane prevents adhering cells from transducing contractile forces to the underlying solid, making studies of cell migration and cellular mechanosensitivity largely impractical. Therefore, the main focus of this review is on polymer-tethered lipid bilayer architectures as biomembrane-mimicking cell substrate. Unlike supported lipid bilayers, these polymer-lipid composite materials enable the free assembly of linkers into linker clusters at cellular contacts without hindering cell spreading and migration and allow the controlled regulation of mechanical properties, enabling studies of cellular mechanosensitivity. The various polymer-tethered lipid bilayer architectures and their complementary properties as cell substrates are discussed.
最近在理解细胞黏附、细胞迁移和细胞机械敏感性方面的突破，得益于具有明确表面特性的工程化细胞底物的发展。传统上，这些底物通过使用可调硬度的配体功能化聚合物凝胶来模拟细胞外基质（ECM）环境。然而，这种 ECM 模拟物在复制细胞-细胞接触处的丰富动力学方面能力有限。本综述重点介绍了更适合分析细胞-细胞界面处细胞黏附、细胞迁移和细胞机械敏感性的细胞表面模拟物的应用。功能化支撑脂质双层系统最初被引入作为生物膜模拟底物，用于研究功能化囊泡（无细胞测定）和贴壁细胞黏附过程中黏附成熟的过程。然而，尽管能够捕获黏附过程，但这种相对简单的平面模型膜的流体脂质双层阻止了附着的细胞将收缩力传递到底层固体，使得细胞迁移和细胞机械敏感性的研究在很大程度上不切实际。因此，本综述的主要重点是聚合物键合脂质双层结构作为生物膜模拟细胞底物。与支撑脂质双层不同，这些聚合物-脂质复合材料允许在细胞接触处自由组装接头形成接头簇，而不会阻碍细胞铺展和迁移，并允许机械性能的受控调节，从而能够研究细胞机械敏感性。讨论了各种聚合物键合脂质双层结构及其作为细胞底物的互补特性。
