Biophysical Society Thematic Meeting | Singapore

Mechanobiology of Disease

Poster Abstracts

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.

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