Cel 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. Dziedzina nauki medical and health sciencesmedical biotechnologytissue engineeringmedical and health sciencesmedical biotechnologycells technologiesstem cellsengineering and technologyindustrial biotechnologybiomaterials Słowa kluczowe mechanobiology multiphysics multiscale mesenchymal stem cell differentiation microfabrication two-photon polymerization synthetic niche substrate cell culture Program(-y) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Temat(-y) ERC-CoG-2014 - ERC Consolidator Grant Zaproszenie do składania wniosków ERC-2014-CoG Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-COG - Consolidator Grant Instytucja przyjmująca POLITECNICO DI MILANO Wkład UE netto € 1 802 830,00 Adres PIAZZA LEONARDO DA VINCI 32 20133 Milano Włochy Zobacz na mapie Region Nord-Ovest Lombardia Milano Rodzaj działalności Higher or Secondary Education Establishments Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 1 802 830,00 Beneficjenci (2) Sortuj alfabetycznie Sortuj według wkładu UE netto Rozwiń wszystko Zwiń wszystko POLITECNICO DI MILANO Włochy Wkład UE netto € 1 802 830,00 Adres PIAZZA LEONARDO DA VINCI 32 20133 Milano Zobacz na mapie Region Nord-Ovest Lombardia Milano Rodzaj działalności Higher or Secondary Education Establishments Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 1 802 830,00 ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI Włochy Wkład UE netto € 100 500,00 Adres VIA MARIO NEGRI 2 20156 Milano Zobacz na mapie Region Nord-Ovest Lombardia Milano Rodzaj działalności Research Organisations Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 100 500,00