Molecular analysis of mechanobiological reactions of human mesenchymal stem cells on biomechanical extracelluar cues induced by magnetically actuated microstructures - µMSC

该项目旨在创建具有明确机械特性的磁致动微结构，并利用这些微结构分析人间充质干细胞（hMSC）在不同局部（生物）机械刺激下的机械生物学反应。为此，将产生柱状和/或纤毛状填充磁性纳米颗粒的微结构。这些结构被设计成在磁场中运动。在柱状结构的情况下，扩展的细胞膜区域将受到生物力学刺激，相反，纤毛状结构将接触（挠痒）细胞膜，而不是局部。根据所产生的刺激，将分析细胞反应，包括：(i)病灶接触动力学，（ii）细胞运动性，即细胞扩散和形态发生，以及肌动蛋白细胞骨架形成可选的板足、丝足和/或应力纤维，以及（iii）细胞功能，包括增殖、分化和凋亡。在这种情况下，实验将旨在阐明hmsc对生物力学线索的反应是否有利于增殖和/或分化，以及可能发生的凋亡保护。将测试刺激的性质、结构大小、弹性模量和表面化学对细胞生物力学反应的影响。我们希望通过对hmsc在不同外部生物力学条件下的反应的了解，可以使用靶向生物力学刺激来诱导所需的细胞反应，并将这一概念引入创新的干细胞牙周治疗概念。

The proposed project aims at creating magnetically actuatable microstructures with well-defined mechanical properties, and to employ these microstructures for analysis of mechanobiological reactions of human mesenchymal stem cells (hMSC) on different local (bio-)mechanical stimuli. To this end, pillar- and/or cilia-like microstructures filled with magnetic nanoparticles will be generated. These structures are designed to be set in motion in a magnetic field. While in case of pillar-like structures extended cell membrane areas will be biomechanically stimulated, cilia-like structures in contrast will touch (tickle) the membrane rather locally. Depending on the resulting stimuli, the cell reactions will be analyzed concerning (i) focal contact dynamics, (ii) cell motility, i.e. cell spreading and morphogenesis as well as actin cytoskeleton formation to optionally lamellipodia, filopodia and/or stress fibres, and (iii) cell functions, including proliferation, differentiation, and apoptosis. In this context, the experiments will aim at shedding light on whether hMSC-response to biomechanical cues will favour proliferation and/or differentiation, and, as the case may be, apoptosis protection will occur. The impact of the nature of the stimulus, the structural sizes, the elasticity moduli, and the surface chemistry on the biomechanical response of the cells will be tested. It is hoped that the gain in knowledge of the hMSC-reactions on qualitatively different external biomechanical cues might allow to use targeted biomechanical stimuli to induce desired cell reactions and introduce this concept into innovative stem cell-based periodontal therapy concepts.