Deformation microscopy expands cell studies


Rebecca Pool

Monday, May 13, 2019 - 15:15
Image: Cells displaying a muscle twitch shown with a high-resolution deformation map. [CSU]
US-based researchers have combined confocal microscopy with a novel algorithm to study the physical properties and deformation dynamics of cells, as never before.
Using the method, Professor Soham Ghosh from Colorado State University and colleagues can generate high-precision, microscopic image-based strain maps of tissues, cells, and nuclei under deformation in vitro and in vivo.
“Deformation microscopy enables detailed, spatially dependent investigations of the cell and nucleus interior in a broad range of physiological and disease applications,” says Ghosh. 
"This technology can drive the field of mechanobiology forward at an unprecedented rate," he adds. "The technique has proven powerful in several applications and is opening new avenues of research."
Left image shows a single beating heart cell with a high-resolution deformation map. Right image shows multiple cells displaying a muscle twitch shown with a high-resolution deformation map. The coloured dots represent individual muscle nucleus. The red and blue colour maps indicate the variation of deformation. Red indicates that cells are extremely tensed (pulled apart); blue indicates that cells are extremely compacted. [Cell Reports]
As Ghosh and colleagues write in Cell Reports, structural heterogeneity is a hallmark of living cells that drives local mechanical properties and dynamic cellular responses.
However, robustly quantifying the intracellular mechanics of cells hasn't been easy using conventional methods.
Given this, the researchers combined confocal microscopy with a so-called hyperelastic warping algorithm to investigate the strain history, deformation dynamics, and changes in structural heterogeneity within the cells.
According to Ghosh, the results were remarkable with the method delivering unhindered images of the cell, and inside the cell nucleus, exposing the missing link between biological systems and the mechanical environment.
By viewing and analysing the cell and nucleus at high magnification, the researchers could study intricate structural architectures and better understand spatially detailed and dynamic cell deformation.
Crucially, the results revealed how the subcellular and subnuclear regions of cells behave in a normal physiological setting versus a diseased setting, representing a huge leap forward in the study of cells to solve human health problems.
Ghosh and colleagues are now set to quantify biological phenomena in cells, to investigate questions surrounding single cell changes in relation to stem cell function.
He and colleagues will study the interaction between the cell's immediate environment, epigenetics, and chromatin architectural organization of the cell nucleus.
"Deformation microscopy will take the research in my lab to new heights, and I look forward to discoveries that will soon unfold due to this groundbreaking advancement," says Ghosh.
Research is published in Cell Reports.
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