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Mechanobiology of nuclear import of transcription factors modeled within a bioengineered stem cell niche.

Objective

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.

Field of science

  • /medical and health sciences/medical biotechnology/cells technologies/stem cells
  • /natural sciences/mathematics/pure mathematics/geometry
  • /natural sciences/physical sciences/optics/laser physics

Call for proposal

ERC-2014-CoG
See other projects for this call

Funding Scheme

ERC-COG - Consolidator Grant

Host institution

POLITECNICO DI MILANO
Address
Piazza Leonardo Da Vinci 32
20133 Milano
Italy
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 802 830

Beneficiaries (2)

POLITECNICO DI MILANO
Italy
EU contribution
€ 1 802 830
Address
Piazza Leonardo Da Vinci 32
20133 Milano
Activity type
Higher or Secondary Education Establishments
ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI
Italy
EU contribution
€ 100 500
Address
Via Mario Negri 2
20156 Milano
Activity type
Research Organisations