Light responsive hydrogels to understand mechanotransduction in cardiac infarctions and muscular dystrophy

• Applicant: Professorin Dr.-Ing. Laura De Laporte
• Subject Area: Biomaterials ; Cell Biology
• Term: since 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 277623886

Cells communicate with each other through mechanical forces, while disruption in such force creation or sensing mechanisms leads to pathological conditions. These forces are difficult to decipher as it is currently not possible to exert native-like strains on cells. The present proposal aims at engineering the light actuating hydrogel platform to improve the current understanding of the mechanobiological origin of diseases, such as cardiac infarctions and muscular dystrophy. Using light responsive hydrogels, we can expose cells to small, local, user-defined forces with spatial and temporal control. The near infra-red micro projection system will be employed to test the effect of different strains to unravel signal transduction mechanisms. The hydrogel properties, such as stiffness and topography, and illumination protocols (duration, frequency, duty cycle, and intensity) will be varied to identify mechanical cues that trigger cells. With regard to cardiovascular diseases, the goal is to mimic the situation in a post-infarct heart, where biochemical factors, such as and inflammatory factors, are superimposed with arythmic contraction. In particular, cardiac fibroblasts are known to form myofibroblasts under such pathogenic conditions but the role that mechanical signals may play on reverting them back to healthy fibroblasts remains unknown. The second goal of this project is to mimic mechanical stresses experienced by cells during exercise and create an in vitro ‘gym for cells’. Healthy cells, as well as cells affected by muscular dystrophy, will be subjected to mechanical stimulation resembling exercise cycles, while their differentiation to myofibers will be studied. We believe that the unique in vitro light-triggered actuating hydrogel platform, engineered in this project, promises advancement in native-like cell manipulation techniques to better understand disease models and will provide realistic data to develop novel therapies and reduce animal experiments, here focused on cardiac infarctions and muscular dystrophy.

• DFG Programme: Research Grants
• International Connection: USA
• Cooperation Partner: Professor Dr. Christian Franck