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Biomaterials. 2018 Oct;181:280-292. doi: 10.1016/j.biomaterials.2018.07.036. Epub 2018 Jul 28.

A systems mechanobiology model to predict cardiac reprogramming outcomes on different biomaterials.

Author information

1
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
2
Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
3
Department of Mechanical and Industrial Engineering, University of Massachusetts, Amherst, MA, USA.
4
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA; Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, USA; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
5
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA; Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: putnam@umich.edu.

Abstract

During normal development, the extracellular matrix (ECM) regulates cell fate mechanically and biochemically. However, the ECM's influence on lineage reprogramming, a process by which a cell's developmental cycle is reversed to attain a progenitor-like cell state followed by subsequent differentiation into a desired cell phenotype, is unknown. Using a material mimetic of the ECM, here we show that ligand identity, ligand density, and substrate modulus modulate indirect cardiac reprogramming efficiency, but were not individually correlated with phenotypic outcomes in a predictive manner. Alternatively, we developed a data-driven model using partial least squares regression to relate short-term cell states, defined by quantitative mechanosensitive responses to different material environments, with long-term changes in phenotype. This model was validated by accurately predicting the reprogramming outcomes on a different material platform. Collectively, these findings suggest a means to rapidly screen candidate biomaterials that support reprogramming with high efficiency, without subjecting cells to the entire reprogramming process.

KEYWORDS:

Heart regeneration; Mechanotransduction; Reprogramming; Systems biology

[Indexed for MEDLINE]
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