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Mechanobiology of Disease
Poster Abstracts
93
65-POS
Board 65
Geometric Confinement of Cells Induces Nuclear Reprogramming
Bibhas Roy
1,2
, Prasuna Ratna
1
.G V. Shivashankar
1,2,3
.
2
The FIRC Institute for Molecular Oncology, Milan, Italy,
1
Mechanobiology Institute,
Singapore, Singapore, Singapore,
3
National University of Singapore, Singapore, Singapore.
Biochemical factors can help reprogram somatic cells into pluripotent stem cells, yet the role of
biophysical factors during reprogramming is unknown. Here, we show that biophysical cues, in
the form of cell geometry and associated confinement, can induce nuclear reprogramming and
significantly improve its efficiency. Establishing and prolonging geometric confinement of
mouse embryonic fibroblast on a fibronectin micropattern of defined shape and size results in
change in the physical properties of nucleus including size, shape, orientation, deformability and
sptio-temporal organization. These transitions in nuclear dynamics induce pronounced change in
lamin A expression, histone acetylation and methylation patterns, which facilitates a stochastic
phase of transdifferentiation, specifically mesenchymal to epithelial transition—an early event in
nuclear reprogramming. We also show that prolonged exposure of this increasing confinement
on these fibroblasts leads to formation of embryonic stem cell like colony and characteristic
biomarkers, suggesting the maturation of nuclear reprogramming. Our work not only establish
biophysical factors as a key regulator of reprogramming, but also elucidating a new correlation
between geometric confinement, epigenetic mechanomodulation and nuclear reprogramming,
which have great implication in regenerative medicine.