Purcell Sean C, Godula Kamil
Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093-0358, USA.
Interface Focus. 2019 Apr 6;9(2):20180080. doi: 10.1098/rsfs.2018.0080. Epub 2019 Feb 15.
The glycocalyx is an information-dense network of biomacromolecules extensively modified through glycosylation that populates the cellular boundary. The glycocalyx regulates biological events ranging from cellular protection and adhesion to signalling and differentiation. Owing to the characteristically weak interactions between individual glycans and their protein binding partners, multivalency of glycan presentation is required for the high-avidity interactions needed to trigger cellular responses. As such, biological recognition at the glycocalyx interface is determined by both the structure of glycans that are present as well as their spatial distribution. While genetic and biochemical approaches have proven powerful in controlling glycan composition, modulating the three-dimensional complexity of the cell-surface 'glycoscape' at the sub-micrometre scale remains a considerable challenge in the field. This focused review highlights recent advances in glycocalyx engineering using synthetic nanoscale glycomaterials, which allows for controlled assembly of complexity with precision not accessible with traditional molecular biology tools. We discuss several exciting new studies in the field that demonstrate the power of precision glycocalyx editing in living cells in revealing and controlling the complex mechanisms by which the glycocalyx regulates biological processes.
糖萼是一个由生物大分子构成的信息密集网络,通过糖基化进行广泛修饰,分布于细胞边界。糖萼调节着从细胞保护、黏附到信号传导和分化等一系列生物学事件。由于单个聚糖与其蛋白质结合伴侣之间的相互作用通常较弱,触发细胞反应所需的高亲和力相互作用需要聚糖呈现的多价性。因此,糖萼界面的生物识别既取决于所存在聚糖的结构,也取决于它们的空间分布。虽然遗传和生化方法已被证明在控制聚糖组成方面很有效,但在亚微米尺度上调节细胞表面“糖景观”的三维复杂性在该领域仍然是一个巨大的挑战。这篇重点综述突出了使用合成纳米级糖材料进行糖萼工程的最新进展,这使得能够以传统分子生物学工具无法达到的精度对复杂性进行可控组装。我们讨论了该领域的几项令人兴奋的新研究,这些研究展示了在活细胞中进行精确糖萼编辑在揭示和控制糖萼调节生物学过程的复杂机制方面的强大作用。