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Cell Rep. 2019 Apr 30;27(5):1607-1620.e4. doi: 10.1016/j.celrep.2019.04.009.

Deformation Microscopy for Dynamic Intracellular and Intranuclear Mapping of Mechanics with High Spatiotemporal Resolution.

Author information

1
Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO, USA.
2
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.
3
Department of Mechanical Engineering, University of Washington, Seattle, WA, USA.
4
Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO, USA; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA. Electronic address: cpneu@colorado.edu.

Abstract

Structural heterogeneity is a hallmark of living cells that drives local mechanical properties and dynamic cellular responses. However, the robust quantification of intracellular mechanics is lacking from conventional methods. Here, we describe the development of deformation microscopy, which leverages conventional imaging and an automated hyperelastic warping algorithm to investigate strain history, deformation dynamics, and changes in structural heterogeneity within the interior of cells and cell nuclei. Using deformation microscopy, we found that partial or complete disruption of LINC complexes in cardiomyocytes in vitro and lamin A/C deficiency in myocytes in vivo abrogate dominant tensile loading in the nuclear interior. We also found that cells cultured on stiff substrates or in hyperosmotic conditions displayed abnormal strain burden and asymmetries at interchromatin regions, which are associated with active transcription. Deformation microscopy represents a foundational approach toward intracellular elastography, with the potential utility to provide mechanistic and quantitative insights in diverse mechanobiological applications.

KEYWORDS:

LINC complex; cell mechanics; chromatin; histone; nuclear mechanobiology; substrate stiffness

PMID:
31042484
DOI:
10.1016/j.celrep.2019.04.009
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