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Nuclear softening expedites interstitial cell migration in fibrous networks and dense connective tissues

Dense matrices impede interstitial cell migration and subsequent repair. We hypothesized that nuclear stiffness is a limiting factor in migration and posited that repair could be expedited by transiently decreasing nuclear stiffness. To test this, we interrogated the interstitial migratory capacity...

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Autores principales: Heo, Su-Jin, Song, Kwang Hoon, Thakur, Shreyasi, Miller, Liane M., Cao, Xuan, Peredo, Ana P., Seiber, Breanna N., Qu, Feini, Driscoll, Tristan P., Shenoy, Vivek B., Lakadamyali, Melike, Burdick, Jason A., Mauck, Robert L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304973/
https://www.ncbi.nlm.nih.gov/pubmed/32596438
http://dx.doi.org/10.1126/sciadv.aax5083
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author Heo, Su-Jin
Song, Kwang Hoon
Thakur, Shreyasi
Miller, Liane M.
Cao, Xuan
Peredo, Ana P.
Seiber, Breanna N.
Qu, Feini
Driscoll, Tristan P.
Shenoy, Vivek B.
Lakadamyali, Melike
Burdick, Jason A.
Mauck, Robert L.
author_facet Heo, Su-Jin
Song, Kwang Hoon
Thakur, Shreyasi
Miller, Liane M.
Cao, Xuan
Peredo, Ana P.
Seiber, Breanna N.
Qu, Feini
Driscoll, Tristan P.
Shenoy, Vivek B.
Lakadamyali, Melike
Burdick, Jason A.
Mauck, Robert L.
author_sort Heo, Su-Jin
collection PubMed
description Dense matrices impede interstitial cell migration and subsequent repair. We hypothesized that nuclear stiffness is a limiting factor in migration and posited that repair could be expedited by transiently decreasing nuclear stiffness. To test this, we interrogated the interstitial migratory capacity of adult meniscal cells through dense fibrous networks and adult tissue before and after nuclear softening via the application of a histone deacetylase inhibitor, Trichostatin A (TSA) or knockdown of the filamentous nuclear protein Lamin A/C. Our results show that transient softening of the nucleus improves migration through microporous membranes, electrospun fibrous matrices, and tissue sections and that nuclear properties and cell function recover after treatment. We also showed that biomaterial delivery of TSA promoted in vivo cellularization of scaffolds by endogenous cells. By addressing the inherent limitations to repair imposed by nuclear stiffness, this work defines a new strategy to promote the repair of damaged dense connective tissues.
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spelling pubmed-73049732020-06-26 Nuclear softening expedites interstitial cell migration in fibrous networks and dense connective tissues Heo, Su-Jin Song, Kwang Hoon Thakur, Shreyasi Miller, Liane M. Cao, Xuan Peredo, Ana P. Seiber, Breanna N. Qu, Feini Driscoll, Tristan P. Shenoy, Vivek B. Lakadamyali, Melike Burdick, Jason A. Mauck, Robert L. Sci Adv Research Articles Dense matrices impede interstitial cell migration and subsequent repair. We hypothesized that nuclear stiffness is a limiting factor in migration and posited that repair could be expedited by transiently decreasing nuclear stiffness. To test this, we interrogated the interstitial migratory capacity of adult meniscal cells through dense fibrous networks and adult tissue before and after nuclear softening via the application of a histone deacetylase inhibitor, Trichostatin A (TSA) or knockdown of the filamentous nuclear protein Lamin A/C. Our results show that transient softening of the nucleus improves migration through microporous membranes, electrospun fibrous matrices, and tissue sections and that nuclear properties and cell function recover after treatment. We also showed that biomaterial delivery of TSA promoted in vivo cellularization of scaffolds by endogenous cells. By addressing the inherent limitations to repair imposed by nuclear stiffness, this work defines a new strategy to promote the repair of damaged dense connective tissues. American Association for the Advancement of Science 2020-06-19 /pmc/articles/PMC7304973/ /pubmed/32596438 http://dx.doi.org/10.1126/sciadv.aax5083 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Heo, Su-Jin
Song, Kwang Hoon
Thakur, Shreyasi
Miller, Liane M.
Cao, Xuan
Peredo, Ana P.
Seiber, Breanna N.
Qu, Feini
Driscoll, Tristan P.
Shenoy, Vivek B.
Lakadamyali, Melike
Burdick, Jason A.
Mauck, Robert L.
Nuclear softening expedites interstitial cell migration in fibrous networks and dense connective tissues
title Nuclear softening expedites interstitial cell migration in fibrous networks and dense connective tissues
title_full Nuclear softening expedites interstitial cell migration in fibrous networks and dense connective tissues
title_fullStr Nuclear softening expedites interstitial cell migration in fibrous networks and dense connective tissues
title_full_unstemmed Nuclear softening expedites interstitial cell migration in fibrous networks and dense connective tissues
title_short Nuclear softening expedites interstitial cell migration in fibrous networks and dense connective tissues
title_sort nuclear softening expedites interstitial cell migration in fibrous networks and dense connective tissues
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304973/
https://www.ncbi.nlm.nih.gov/pubmed/32596438
http://dx.doi.org/10.1126/sciadv.aax5083
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