Single cell imaging of nuclear architecture changes
Brandstrup Morrish, R; Hermes, M; Metz, J; et al.Stone, N; Pagliara, S; Chahwan, R; Palombo, F
Date: 24 July 2019
Journal
Frontiers in Cell Development and Biology
Publisher
Frontiers Media
Publisher DOI
Abstract
The dynamic architecture of chromatin, the macromolecular complex comprised primarily of
DNA and histones, is vital for eukaryotic cell growth. Chemical and conformational changes to
chromatin are important markers of functional and developmental processes in cells. However,
chromatin architecture regulation has not yet been fully ...
The dynamic architecture of chromatin, the macromolecular complex comprised primarily of
DNA and histones, is vital for eukaryotic cell growth. Chemical and conformational changes to
chromatin are important markers of functional and developmental processes in cells. However,
chromatin architecture regulation has not yet been fully elucidated. Therefore, novel approaches
to assessing chromatin changes at the single-cell level are required. Here we report the use of
FTIR imaging and microfluidic cell-stretcher chips to assess changes to chromatin architecture
and its effect on the mechanical properties of the nucleus in immune cells. FTIR imaging enables
label-free chemical imaging with subcellular resolution. By optimizing the FTIR methodology
and couple it with cell segmentation analysis approach, we have identified key spectral changes
corresponding to changes in DNA levels and chromatin conformation at the single cell level. By
further manipulating live single cells using pressure-driven microfluidics, we found that
chromatin decondensation – either during general transcriptional activation or during specific
immune cell maturation – can ultimately lead to nuclear auxeticity which is a new biological
phenomenon recently identified. Taken together our findings demonstrate the tight and,
potentially bilateral, link between extra-cellular mechanotransduction and intra-cellular nuclear
architecture.
Physics and Astronomy
Faculty of Environment, Science and Economy
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