Significance of cellular surface factors for the selective cytotoxicity of antimicrobial peptides (AMPs) against cancer cells

该项目的目标是了解抗菌肽与人类癌细胞相互作用的动力学，以及基于细胞表面（糖基）结构的存在和/或形状对肽-细胞相互作用有重大影响的假设的差异细胞毒性和作用模式的分子基础。我们将全面分析肽与人类癌细胞系的相互作用，这些细胞系自然或人为地在带负电荷的聚糖（如唾液酸）的表面暴露或糖萼的厚度上有所不同。该应用程序的核心仪器是一个代谢芯片生物传感器，它可以评估重要的细胞生理参数的动态。为了将多肽的生物活性与细胞表面分子的存在和化学结构联系起来，生物学数据将通过多肽-膜相互作用的研究来补充，例如膜结合、插层和渗透，使用由磷脂和糖脂组成的人工膜来模拟正常和异常细胞的不同组成的膜。

The objectives of this project are to gain an understanding of the dynamics of the interactions of antimicrobial peptides with human cancer cells and the molecular basis for differential cytotoxicity and mode of action based on the hypothesis that the presence and/or shape of the cellular surface (glyco)-structures have a significant impact on peptide-cell interaction. We will comprehensively analyse peptide interactions with human cancer cell lines, which naturally or artificially differ in the surface exposition of negatively charged glycans (e.g. sialic acids) or in the thickness of the glycocalyx. The core instrumentation of this application is a metabolic chip biosensor, which enables the assessment of the dynamics of important cell physiological parameters. To correlate the biological activities of peptides with the presence and chemical structure of cellular surface molecules, the biological data will be complemented by peptide-membrane interaction studies, e.g. membrane binding, intercalation, and permeabilization, using artificial membranes composed of phospholipids and glycolipids to mimic the differently composed membranes of normal and aberrant cells.