Objetivo Many therapeutic applications of stem cells require accurate control of their differentiation. To this purpose there is a major ongoing effort in the development of advanced culture substrates to be used as “synthetic niches” for the cells, mimicking the native ones. The goal of this project is to use a synthetic niche cell culture model to test my revolutionary hypothesis that in stem cell differentiation, nuclear import of gene-regulating transcription factors is controlled by the stretch of the nuclear pore complexes. If verified, this idea could lead to a breakthrough in biomimetic approaches to engineering stem cell differentiation.I investigate this question specifically in mesenchymal stem cells (MSC), because they are adherent and highly mechano-sensitive to architectural cues of the microenvironment. To verify my hypothesis I will use a combined experimental-computational model of mechanotransduction. I will a) scale-up an existing three-dimensional synthetic niche culture substrate, fabricated by two-photon laser polymerization, b) characterize the effect of tridimensionality on the differentiation fate of MSC cultured in the niches, c) develop a multiphysics/multiscale computational model of nuclear import of transcription factors within differentially-spread cultured cells, and d) integrate the numerical predictions with experimentally-measured import of fluorescently-labelled transcription factors.This project requires the synergic combination of several advanced bioengineering technologies, including micro/nano fabrication and biomimetics. The use of two-photon laser polymerization for controlling the geometry of the synthetic cell niches is very innovative and will highly impact the fields of bioengineering and biomaterial technology. A successful outcome will lead to a deeper understanding of bioengineering methods to direct stem cell fate and have therefore a significant impact in tissue repair technologies and regenerative medicine. Ámbito científico medical and health sciencesmedical biotechnologytissue engineeringmedical and health sciencesmedical biotechnologycells technologiesstem cellsengineering and technologyindustrial biotechnologybiomaterials Palabras clave mechanobiology multiphysics multiscale mesenchymal stem cell differentiation microfabrication two-photon polymerization synthetic niche substrate cell culture Programa(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Tema(s) ERC-CoG-2014 - ERC Consolidator Grant Convocatoria de propuestas ERC-2014-CoG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-COG - Consolidator Grant Institución de acogida POLITECNICO DI MILANO Aportación neta de la UEn € 1 802 830,00 Dirección PIAZZA LEONARDO DA VINCI 32 20133 Milano Italia Ver en el mapa Región Nord-Ovest Lombardia Milano Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 1 802 830,00 Beneficiarios (2) Ordenar alfabéticamente Ordenar por aportación neta de la UE Ampliar todo Contraer todo POLITECNICO DI MILANO Italia Aportación neta de la UEn € 1 802 830,00 Dirección PIAZZA LEONARDO DA VINCI 32 20133 Milano Ver en el mapa Región Nord-Ovest Lombardia Milano Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 1 802 830,00 ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI Italia Aportación neta de la UEn € 100 500,00 Dirección VIA MARIO NEGRI 2 20156 Milano Ver en el mapa Región Nord-Ovest Lombardia Milano Tipo de actividad Research Organisations Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 100 500,00