Deformation Microscopy for Dynamic Intracellular and Intranuclear Mapping of Mechanics with High Spatiotemporal Resolution
Summary: 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, whi...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-04-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719304644 |
| _version_ | 1828393622579445760 |
|---|---|
| author | Soham Ghosh Benjamin Seelbinder Jonathan T. Henderson Ryan D. Watts Adrienne K. Scott Alexander I. Veress Corey P. Neu |
| author_facet | Soham Ghosh Benjamin Seelbinder Jonathan T. Henderson Ryan D. Watts Adrienne K. Scott Alexander I. Veress Corey P. Neu |
| author_sort | Soham Ghosh |
| collection | DOAJ |
| description | Summary: 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. : Ghosh et al. show that deformation microscopy, a technique based on image analysis and mechanics, reveals deformation dynamics and structural heterogeneity changes for several applications and at multiple scales, including tissues, cells, and nuclei. They reveal how the disruption of nuclear proteins and pathological conditions abrogate mechanical strain in the nuclear interior. Keywords: nuclear mechanobiology, LINC complex, cell mechanics, chromatin, substrate stiffness, histone |
| first_indexed | 2024-12-10T07:40:52Z |
| format | Article |
| id | doaj.art-1c231d10b10f4aceb80907dfab44df65 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T07:40:52Z |
| publishDate | 2019-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-1c231d10b10f4aceb80907dfab44df652022-12-22T01:57:18ZengElsevierCell Reports2211-12472019-04-0127516071620.e4Deformation Microscopy for Dynamic Intracellular and Intranuclear Mapping of Mechanics with High Spatiotemporal ResolutionSoham Ghosh0Benjamin Seelbinder1Jonathan T. Henderson2Ryan D. Watts3Adrienne K. Scott4Alexander I. Veress5Corey P. Neu6Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO, USADepartment of Mechanical Engineering, University of Colorado Boulder, Boulder, CO, USAWeldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USAWeldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USADepartment of Mechanical Engineering, University of Colorado Boulder, Boulder, CO, USADepartment of Mechanical Engineering, University of Washington, Seattle, WA, USADepartment of Mechanical Engineering, University of Colorado Boulder, Boulder, CO, USA; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA; Corresponding authorSummary: 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. : Ghosh et al. show that deformation microscopy, a technique based on image analysis and mechanics, reveals deformation dynamics and structural heterogeneity changes for several applications and at multiple scales, including tissues, cells, and nuclei. They reveal how the disruption of nuclear proteins and pathological conditions abrogate mechanical strain in the nuclear interior. Keywords: nuclear mechanobiology, LINC complex, cell mechanics, chromatin, substrate stiffness, histonehttp://www.sciencedirect.com/science/article/pii/S2211124719304644 |
| spellingShingle | Soham Ghosh Benjamin Seelbinder Jonathan T. Henderson Ryan D. Watts Adrienne K. Scott Alexander I. Veress Corey P. Neu Deformation Microscopy for Dynamic Intracellular and Intranuclear Mapping of Mechanics with High Spatiotemporal Resolution Cell Reports |
| title | Deformation Microscopy for Dynamic Intracellular and Intranuclear Mapping of Mechanics with High Spatiotemporal Resolution |
| title_full | Deformation Microscopy for Dynamic Intracellular and Intranuclear Mapping of Mechanics with High Spatiotemporal Resolution |
| title_fullStr | Deformation Microscopy for Dynamic Intracellular and Intranuclear Mapping of Mechanics with High Spatiotemporal Resolution |
| title_full_unstemmed | Deformation Microscopy for Dynamic Intracellular and Intranuclear Mapping of Mechanics with High Spatiotemporal Resolution |
| title_short | Deformation Microscopy for Dynamic Intracellular and Intranuclear Mapping of Mechanics with High Spatiotemporal Resolution |
| title_sort | deformation microscopy for dynamic intracellular and intranuclear mapping of mechanics with high spatiotemporal resolution |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719304644 |
| work_keys_str_mv | AT sohamghosh deformationmicroscopyfordynamicintracellularandintranuclearmappingofmechanicswithhighspatiotemporalresolution AT benjaminseelbinder deformationmicroscopyfordynamicintracellularandintranuclearmappingofmechanicswithhighspatiotemporalresolution AT jonathanthenderson deformationmicroscopyfordynamicintracellularandintranuclearmappingofmechanicswithhighspatiotemporalresolution AT ryandwatts deformationmicroscopyfordynamicintracellularandintranuclearmappingofmechanicswithhighspatiotemporalresolution AT adriennekscott deformationmicroscopyfordynamicintracellularandintranuclearmappingofmechanicswithhighspatiotemporalresolution AT alexanderiveress deformationmicroscopyfordynamicintracellularandintranuclearmappingofmechanicswithhighspatiotemporalresolution AT coreypneu deformationmicroscopyfordynamicintracellularandintranuclearmappingofmechanicswithhighspatiotemporalresolution |