Energetic investigations of induced particle uptake in functionalized, synthetic membrane systems.

对功能化合成膜系统中诱导颗粒吸收的积极研究。

• 批准号: 280366404
• 负责人: Professor Dr. Alexander Rohrbach
• 金额: --
• 依托单位: Institut für Mikrosystemtechnik (IMTEK)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/280366404?language=en
• 关键词: Energetic; investigations; induced; particle; uptake

Living cells take up bacteria into their interior typically by phagocytosis, if both mechano-chemical signals and the required energy can be summoned up. In particular, macrophages, as part of our immune system, take up bacteria, but also uncoated particles, which is only possible by the interplay of different biophysical forces. For a better analysis of the relevant forces and to better assess the role of known factors during phagocytosis, a possible approach is to use biomimetic systems, which show a significantly reduced complexity relative to a cell. The simplest biomimetic variant of the cell is a giant unilamellar vesicle (GUV), where the chemical and mechanical properties of the spherical lipid bilayer can be manipulated in many different ways. In order to engulf and uptake a particle, the membrane of the GUV has to be deformed significantly. In a recent study it could be shown that the adhesion energy released during particle binding and wrapping can compensate the energy costs for membrane deformation and that cytoskeleton forces were dispensable. The goal of the collaborative proposal of the working groups Rohrbach and Römer is to better understand the physical mechanisms of particle uptake, in particular the role of the membrane deformation. In this context, we want to establish two complementary measurement techniques allowing to determine the energetics during particle uptake into an artificial cell (GUV). By using a photonic force microscope for small and medium uptake forces and an atomic force microscope for medium and larger forces, a particle will be approached in a controlled manner to the membrane, while the particle displacements are measured precisely to determine the changes in force and energy. In a bottom-up approach we will add stepwise more complexity to the biomimetic system, such that the force and energy profiles during particle uptake are measured always with exactly the same experimental scheme. On the one hand the complexity of the system can be increased by adding different lipids and receptors into the GUV membrane, on the other hand the size, the shape / orientation and the surface functionalization of the particle will be changed in a well-controlled manner. Mathematical modelling will help to improve the mechanistic understanding during particle uptake and to better interpret the experimental data.

活细胞通常通过吞噬作用将细菌吸收到其内部，如果机械化学信号和所需能量都可以被召集起来的话。特别是，巨噬细胞作为我们免疫系统的一部分，不仅可以吸收细菌，还可以吸收未涂层的颗粒，这只能通过不同生物物理力的相互作用来实现。为了更好地分析相关的力量，并更好地评估已知因素在吞噬作用中的作用，一种可能的方法是使用仿生系统，其显示出相对于细胞显着降低的复杂性。细胞的最简单的仿生变体是巨大的单层囊泡（GUV），其中球形脂质双层的化学和机械性质可以以许多不同的方式进行操纵。为了吞噬和摄取颗粒，GUV的膜必须显著变形。在最近的一项研究中，可以表明，在颗粒结合和包裹过程中释放的粘附能可以补偿膜变形的能量消耗，并且细胞骨架力被抵消。Rohrbach和Römer工作组合作提案的目标是更好地了解颗粒摄取的物理机制，特别是膜变形的作用。在这种情况下，我们希望建立两个互补的测量技术，允许确定在粒子吸收到人工细胞（GUV）的能量。通过使用光子力显微镜用于小的和中等的摄取力，以及原子力显微镜用于中等和较大的力，粒子将以受控的方式接近膜，同时精确测量粒子位移以确定力和能量的变化。在自下而上的方法中，我们将逐步增加仿生系统的复杂性，以便始终使用完全相同的实验方案测量粒子摄取过程中的力和能量分布。一方面，可以通过向GUV膜中添加不同的脂质和受体来增加系统的复杂性，另一方面，颗粒的尺寸、形状/取向和表面官能化将以良好控制的方式改变。数学建模将有助于提高颗粒吸收过程中的机械理解，并更好地解释实验数据。

项目成果

The Lectin LecA Sensitizes the Human Stretch-Activated Channel TREK-1 but Not Piezo1 and Binds Selectively to Cardiac Non-myocytes

• DOI: 10.3389/fphys.2020.00457
• 发表时间: 2020-05-15
• 期刊: FRONTIERS IN PHYSIOLOGY
• 影响因子: 4
• 作者: Darkow, Elisa;Rog-Zielinska, Eva A.;Peyronnet, Remi
• 通讯作者: Peyronnet, Remi

Differential recognition of lipid domains by two Gb3-binding lectins

两种 Gb3 结合凝集素对脂质结构域的差异识别

• DOI: 10.1038/s41598-020-66522-8
• 发表时间: 2020
• 期刊: Scientific Reports
• 影响因子: 4.6
• 作者: Schubert T;Sych T;Madl J;Omidvar R;Patalag LJ;Ries A;Kettelhoit K;Brandel A;Mely Y;Steinem C;Werz DB;Thuenauer R;Römer W
• 通讯作者: Römer W