Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, and Emory University, Atlanta, GA 30322, United States.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, and Emory University, Atlanta, GA 30322, United States; Department of Chemistry, Emory University, Atlanta, GA 30322, United States..
Biochim Biophys Acta Biomembr. 2017 Sep;1859(9 Pt A):1465-1482. doi: 10.1016/j.bbamem.2017.05.005. Epub 2017 May 11.
Mammalian and bacterial cells sense and exert mechanical forces through the process of mechanotransduction, which interconverts biochemical and physical signals. This is especially important in contact-dependent signaling, where ligand-receptor binding occurs at cell-cell or cell-ECM junctions. By virtue of occurring within these specialized junctions, receptors engaged in contact-dependent signaling undergo oligomerization and coupling with the cytoskeleton as part of their signaling mechanisms. While our ability to measure and map biochemical signaling within cell junctions has advanced over the past decades, physical cues remain difficult to map in space and time. Recently, supported lipid bilayer (SLB) technologies have emerged as a flexible platform to mimic and perturb cell-cell and cell-ECM junctions, allowing one to study membrane receptor mechanotransduction. Changing the lipid composition and underlying substrate tunes bilayer fluidity, and lipid and ligand micro- and nano-patterning spatially control positioning and clustering of receptors. Patterning metal gridlines within SLBs confines lipid mobility and introduces mechanical resistance. Here we review fundamental SLB mechanics and how SLBs can be engineered as tunable cell substrates for mechanotransduction studies. Finally, we highlight the impact of this work in understanding the biophysical mechanisms of cell adhesion. This article is part of a Special Issue entitled: Interactions between membrane receptors in cellular membranes edited by Kalina Hristova.
哺乳动物和细菌细胞通过力学转导过程来感知和施加机械力,该过程将生化信号和物理信号相互转换。这在依赖接触的信号传递中尤为重要,因为配体-受体结合发生在细胞-细胞或细胞-细胞外基质连接处。由于发生在这些专门的连接处,参与依赖接触的信号传递的受体发生寡聚化,并与细胞骨架偶联,作为其信号机制的一部分。虽然我们测量和绘制细胞连接处生化信号的能力在过去几十年中得到了提高,但物理线索在空间和时间上仍然难以绘制。最近,支持脂质双层 (SLB) 技术作为一种灵活的平台出现,可模拟和干扰细胞-细胞和细胞-细胞外基质连接处,从而研究膜受体的力学转导。改变脂质组成和底层底物可以调节双层流动性,并且脂质和配体的微纳图案化可以空间控制受体的定位和聚类。在 SLB 内形成金属网格线会限制脂质的流动性并引入机械阻力。在这里,我们回顾了基本的 SLB 力学以及如何将 SLB 设计为用于力学转导研究的可调谐细胞底物。最后,我们强调了这项工作在理解细胞黏附的生物物理机制方面的影响。本文是由 Kalina Hristova 编辑的题为“细胞膜中膜受体的相互作用”的特刊的一部分。