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Title:
Nuclear Deformability Constitutes a Rate-Limiting Step During Cell Migration in 3-D Environments | Cellular and Molecular Bioengineering
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Cell motility plays a critical role in many physiological and pathological settings, ranging from wound healing to cancer metastasis. While cell migration on 2-dimensional (2-D) substrates has been studied for decades, the physical challenges cells face when moving in 3-D environments are only now emerging. In particular, the cell nucleus, which occupies a large fraction of the cell volume and is normally substantially stiffer than the surrounding cytoplasm, may impose a major obstacle when cells encounter narrow constrictions in the interstitial space, the extracellular matrix, or small capillaries. Using novel microfluidic devices that allow observation of cells moving through precisely defined geometries at high spatial and temporal resolution, we determined nuclear deformability as a critical factor in the cells’ ability to pass through constrictions smaller than the size of the nucleus. Furthermore, we found that cells with reduced levels of the nuclear envelope proteins lamins A/C, which are the main determinants of nuclear stiffness, passed significantly faster through narrow constrictions during active migration and passive perfusion. Given recent reports that many human cancers have altered lamin expression, our findings suggest a novel biophysical mechanism by which changes in nuclear structure and composition may promote cancer cell invasion and metastasis.
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Keywords {🔍}
article, cell, google, scholar, nuclear, migration, lammerding, nucleus, biol, lamin, cancer, cells, video, constriction, time, mechanics, national, sci, envelope, content, science, usa, migrating, engineering, research, davidson, jan, stewart, cornell, department, award, lmna, white, beginning, left, transit, measurements, privacy, cookies, metastasis, physical, narrow, human, progeria, breast, hodzic, proc, natl, acad, friedl,
Topics {✒️}
hutchinson–gilford progeria syndrome month download article/chapter hutchinson–gilford progeria leads platelet-derived growth factor hutchinson–gilford progeria cells intracellular stress-bearing organelle harvard medical school/brigham enhances matrix-directed differentiation american heart association representative time-lapse video nuclear deformability constitutes progeria research foundation altered lamin expression cancer cell metastasis determine nuclear shape bakshi & jan lammerding receptor mrna expression measure nuclear mechanics jan lammerding declare nuclear envelope reduces cell motility privacy choices/manage cookies neutrophil-type cells determined nuclear deformability human breast cancer author information authors molecular bioengineering aims flow-induced hardening defective nuclear mechanics nuclear protein kinase analyzing cell mechanics pilot project award award number u54ca143876 full article pdf national cancer institute nuclear lamin stiffness national science foundation anchoring transmembrane actin broken nuclei—lamins migration transit time fifteen years access cancer metastasis stem cell differentiation migrating langerhans cells european economic area rate-limiting step passed significantly faster related subjects striated muscle disease view
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headline:Nuclear Deformability Constitutes a Rate-Limiting Step During Cell Migration in 3-D Environments
description:Cell motility plays a critical role in many physiological and pathological settings, ranging from wound healing to cancer metastasis. While cell migration on 2-dimensional (2-D) substrates has been studied for decades, the physical challenges cells face when moving in 3-D environments are only now emerging. In particular, the cell nucleus, which occupies a large fraction of the cell volume and is normally substantially stiffer than the surrounding cytoplasm, may impose a major obstacle when cells encounter narrow constrictions in the interstitial space, the extracellular matrix, or small capillaries. Using novel microfluidic devices that allow observation of cells moving through precisely defined geometries at high spatial and temporal resolution, we determined nuclear deformability as a critical factor in the cells’ ability to pass through constrictions smaller than the size of the nucleus. Furthermore, we found that cells with reduced levels of the nuclear envelope proteins lamins A/C, which are the main determinants of nuclear stiffness, passed significantly faster through narrow constrictions during active migration and passive perfusion. Given recent reports that many human cancers have altered lamin expression, our findings suggest a novel biophysical mechanism by which changes in nuclear structure and composition may promote cancer cell invasion and metastasis.
datePublished:2014-06-20T00:00:00Z
dateModified:2014-06-20T00:00:00Z
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Mechanics
Cancer
Microfluidics
Microstructures
Metastasis
Invasion
Nuclear envelope
Biomedical Engineering and Bioengineering
Biomedical Engineering/Biotechnology
Biological and Medical Physics
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Biomaterials
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headline:Nuclear Deformability Constitutes a Rate-Limiting Step During Cell Migration in 3-D Environments
description:Cell motility plays a critical role in many physiological and pathological settings, ranging from wound healing to cancer metastasis. While cell migration on 2-dimensional (2-D) substrates has been studied for decades, the physical challenges cells face when moving in 3-D environments are only now emerging. In particular, the cell nucleus, which occupies a large fraction of the cell volume and is normally substantially stiffer than the surrounding cytoplasm, may impose a major obstacle when cells encounter narrow constrictions in the interstitial space, the extracellular matrix, or small capillaries. Using novel microfluidic devices that allow observation of cells moving through precisely defined geometries at high spatial and temporal resolution, we determined nuclear deformability as a critical factor in the cells’ ability to pass through constrictions smaller than the size of the nucleus. Furthermore, we found that cells with reduced levels of the nuclear envelope proteins lamins A/C, which are the main determinants of nuclear stiffness, passed significantly faster through narrow constrictions during active migration and passive perfusion. Given recent reports that many human cancers have altered lamin expression, our findings suggest a novel biophysical mechanism by which changes in nuclear structure and composition may promote cancer cell invasion and metastasis.
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Microfluidics
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Biomedical Engineering and Bioengineering
Biomedical Engineering/Biotechnology
Biological and Medical Physics
Biophysics
Biomaterials
Cell Biology
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