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Abstract Extracellular matrices of living tissues exhibit viscoelastic properties, yet how these properties regulate chromatin and the epigenome remains unclear. Here, we show that viscoelastic substrates induce changes in nuclear architecture and epigenome, with more pronounced effects on softer surfaces. Fibroblasts on viscoelastic substrates display larger nuclei, lower chromatin compaction, and differential expression of distinct sets of genes related to the cytoskeleton and nuclear function, compared to those on elastic surfaces. Slow-relaxing viscoelastic substrates reduce lamin A/C expression and enhance nuclear remodeling. These structural changes are accompanied by a global increase in euchromatin marks and local increase in chromatin accessibility atcis-regulatory elements associated with neuronal and pluripotent genes. Consequently, viscoelastic substrates improve the reprogramming efficiency from fibroblasts into neurons and induced pluripotent stem cells. Collectively, our findings unravel the roles of matrix viscoelasticity in epigenetic regulation and cell reprogramming, with implications for designing smart materials for cell fate engineering. 

Abstract A new device termed “Optomagnetic Micromirror Arrays” (OMA) is demonstrated capable of mapping the stiffness distribution of biomimetic materials across a 5.1 mm × 7.2 mm field of view with cellular resolution. The OMA device comprises an array of 50 000 magnetic micromirrors with optical grating structures embedded beneath an elastic PDMS film, with biomimetic materials affixed on top. Illumination of a broadband white light beam onto these micromirrors results in the reflection of microscale rainbow light rays on each micromirror. When a magnetic field is applied, it causes each micromirror to tilt differently depending on the local stiffness of the biomimetic materials. Through imaging these micromirrors with low N.A. optics, a specific narrow band of reflection light rays from each micromirror is captured. Changing a micromirror's tilt angle also alters the color spectrum it reflects back to the imaging system and the color of the micromirror image it represents. As a result, OMA can infer the local stiffness of the biomimetic materials through the color change detected on each micromirror. OMA offers the potential for high‐throughput stiffness mapping at the tissue‐level while maintaining spatial resolution at the cellular level. 

Abstract The role of transcription factors and biomolecules in cell type conversion has been widely studied. Yet, it remains unclear whether and how intracellular mechanotransduction through focal adhesions (FAs) and the cytoskeleton regulates the epigenetic state and cell reprogramming. Here, it is shown that cytoskeletal structures and the mechanical properties of cells are modulated during the early phase of induced neuronal (iN) reprogramming, with an increase in actin cytoskeleton assembly induced by Ascl1 transgene. The reduction of actin cytoskeletal tension or cell adhesion at the early phase of reprogramming suppresses the expression of mesenchymal genes, promotes a more open chromatin structure, and significantly enhances the efficiency of iN conversion. Specifically, reduction of intracellular tension or cell adhesion not only modulates global epigenetic marks, but also decreases DNA methylation and heterochromatin marks and increases euchromatin marks at the promoter of neuronal genes, thus enhancing the accessibility for gene activation. Finally, micro‐ and nano‐topographic surfaces that reduce cell adhesions enhance iN reprogramming. These novel findings suggest that the actin cytoskeleton and FAs play an important role in epigenetic regulation for cell fate determination, which may lead to novel engineering approaches for cell reprogramming.