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

磁驱动微结构诱导的人间充质干细胞对生物力学细胞外信号的机械生物学反应的分子分析 - µMSC

• 批准号: 254846193
• 负责人: Professor Dr. Jürgen Rühe
• 金额: --
• 依托单位: Abteilung für Orale Biotechnologie
• 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/254846193?language=en
• 关键词: Molecular; analysis; mechanobiological; reactions; human

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.

该项目旨在创建具有明确机械性能的磁致动微结构，并将这些微结构用于分析人骨髓间充质干细胞(HMSC)对不同局部(生物)机械刺激的机械生物学反应。为此，将产生填充磁性纳米颗粒的柱状和/或纤毛状微结构。这些结构被设计成在磁场中运动。在柱状结构的情况下，延长的细胞膜区域将受到生物力学的刺激，而纤毛状结构则会接触(挠)膜，而不是局部。根据产生的刺激，将分析细胞的反应，涉及(I)焦点接触动力学，(Ii)细胞运动，即细胞的扩散和形态发生，以及肌动蛋白细胞骨架的形成，可选的片状脂肪细胞、丝状伪足和/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，这些实验的目的是阐明hMSC对生物力学信号的反应是否有利于增殖和/或分化，以及是否会发生凋亡保护。将测试刺激的性质、结构尺寸、弹性模数和表面化学对细胞生物力学响应的影响。人们希望，对hMSC在不同外部生物力学信号上的反应的了解可能会允许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基于干细胞的牙周治疗概念。

项目成果

Disruption of adherens junction and alterations in YAP-related proliferation behavior as part of the underlying cell transformation process of alcohol-induced oral carcinogenesis.

粘附连接的破坏和 YAP 相关增殖行为的改变是酒精诱导口腔癌发生的潜在细胞转化过程的一部分

• DOI: 10.1016/j.bbamcr.2017.10.015
• 发表时间: 2018
• 期刊: Biochimica et biophysica acta. Molecular cell research
• 作者: Ayman Husari;Diana Hülter-Hassler;Thorsten Steinberg;Simon Daniel Schulz;Pascal Tomakidi
• 通讯作者: Pascal Tomakidi