Ding’s group revealed that material surface topography regulated nuclear shape, chromosomal repositioning and gene expressions of cells

As is known from interdisciplinary research about biomaterials, chemical biology, cell biology and regenerative medicine, biomaterial surfaces can lead to various cell responses. Recently, Ding’s group has revealed that well designed surface topography can even induce severe nuclear deformation, chromosomal repositioning and changes of gene expression.

With a silicon micropit template prepared with microelectronics manufacturing technology, Ding’s group prepared micropillar arrays of PLGA, an important polymeric material. Under an appropriate micropillar array, cell nuclei exhibited significant self deformation, as shown in Figure 1.

Figure 1. Cell nuclear deformation on a PLGA micropillar array. (A) SEM image of the PLGA micropillar array. (B) Fluorescence images of the nuclei of HeLa cells on the PLGA micropillar array and smooth surface.

Ding’s group further elicited two questions: will the positioning of some chromosomes change on the micropillar array in comparison with those on the smooth surface, and will gene expressions of the cells vary on the topological surfaces along with nuclear deformation? To this end, fluorescence in situ hybridization (FISH) was employed to detect the radial disposition of chromosomes 18 and 19 (Figure 2). These chromosomes were selected as two models, because chromosomes 18 and 19 have similar DNA contents but contrasting gene densities, and are typical for examination of chromosomal territory. It was indicated that chromosomes 18 and 19 moved towards the nuclear periphery in response to the cell nuclear deformation on the micropillar array, with chromosome 18 translocated much closer to the cell nuclear periphery.

Figure 2. FISH staining for monitoring chromosomal territories of chromosomes 18 and 19 of HeLa cells on the micropillar array and smooth surface. (A) Principle of fluorescence in situ hybridization (FISH). (B) 3D and 2D fluorescence images of chromosomes 18 and 19. The chromosomes were hybridized with whole-chromosome painting probes with orange fluorochrome, and the nuclei were stained blue with DAPI.

DNA microarray technology was also used to detect the gene expression profiles of the cells on the PLGA micropillar array (Figure 3). It was found that 180 genes were up-regulated and 255 genes down-regulated for the cells on the micropillar array. The corresponding transcriptome was further investigated via Bioinformatics using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.

The article was published in the journal of ACS Applied Materials & Interfaces in August, 2020. The first author is Dr. Ruili LIU and the corresponding author is Prof. Jiandong DING.

Publication link: https://dx.doi.org/10.1021/acsami.0c05883