Effects of substrate stiffness and actin velocity on in silico fibronectin fibril morphometry and mechanics.

Assembly of the extracellular matrix protein fibronectin (FN) into insoluble, viscoelastic fibrils is a critical step during embryonic development and wound healing; misregulation of FN fibril assembly has been implicated in many diseases, including fibrotic diseases and cancer. We have previously d...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Seth H Weinberg, Navpreet Saini, Christopher A Lemmon
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9e356f9430e047159fdb053b0e944480
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:9e356f9430e047159fdb053b0e944480
record_format	dspace
spelling	oai:doaj.org-article:9e356f9430e047159fdb053b0e9444802021-12-02T20:10:57ZEffects of substrate stiffness and actin velocity on in silico fibronectin fibril morphometry and mechanics.1932-620310.1371/journal.pone.0248256https://doaj.org/article/9e356f9430e047159fdb053b0e9444802021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0248256https://doaj.org/toc/1932-6203Assembly of the extracellular matrix protein fibronectin (FN) into insoluble, viscoelastic fibrils is a critical step during embryonic development and wound healing; misregulation of FN fibril assembly has been implicated in many diseases, including fibrotic diseases and cancer. We have previously developed a computational model of FN fibril assembly that recapitulates the morphometry and mechanics of cell-derived FN fibrils. Here we use this model to probe two important questions: how is FN fibril formation affected by the contractile phenotype of the cell, and how is FN fibril formation affected by the stiffness of the surrounding tissue? We show that FN fibril formation depends strongly on the contractile phenotype of the cell, but only weakly on in vitro substrate stiffness, which is an analog for in vivo tissue stiffness. These results are consistent with previous experimental data and provide a better insight into conditions that promote FN fibril assembly. We have also investigated two distinct phenotypes of FN fibrils that we have previously identified; we show that the ratio of the two phenotypes depends on both substrate stiffness and contractile phenotype, with intermediate contractility and high substrate stiffness creating an optimal condition for stably stretched fibrils. Finally, we have investigated how re-stretch of a fibril affects cellular response. We probed how the contractile phenotype of the re-stretching cell affects the mechanics of the fibril; results indicate that the number of myosin motors only weakly affects the cellular response, but increasing actin velocity results in a decrease in the apparent stiffness of the fibril and a decrease in the stably-applied force to the fibril. Taken together, these results give novel insights into the combinatorial effects of substrate stiffness and cell contractility on FN fibril assembly.Seth H WeinbergNavpreet SainiChristopher A LemmonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0248256 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Seth H Weinberg Navpreet Saini Christopher A Lemmon Effects of substrate stiffness and actin velocity on in silico fibronectin fibril morphometry and mechanics.
description	Assembly of the extracellular matrix protein fibronectin (FN) into insoluble, viscoelastic fibrils is a critical step during embryonic development and wound healing; misregulation of FN fibril assembly has been implicated in many diseases, including fibrotic diseases and cancer. We have previously developed a computational model of FN fibril assembly that recapitulates the morphometry and mechanics of cell-derived FN fibrils. Here we use this model to probe two important questions: how is FN fibril formation affected by the contractile phenotype of the cell, and how is FN fibril formation affected by the stiffness of the surrounding tissue? We show that FN fibril formation depends strongly on the contractile phenotype of the cell, but only weakly on in vitro substrate stiffness, which is an analog for in vivo tissue stiffness. These results are consistent with previous experimental data and provide a better insight into conditions that promote FN fibril assembly. We have also investigated two distinct phenotypes of FN fibrils that we have previously identified; we show that the ratio of the two phenotypes depends on both substrate stiffness and contractile phenotype, with intermediate contractility and high substrate stiffness creating an optimal condition for stably stretched fibrils. Finally, we have investigated how re-stretch of a fibril affects cellular response. We probed how the contractile phenotype of the re-stretching cell affects the mechanics of the fibril; results indicate that the number of myosin motors only weakly affects the cellular response, but increasing actin velocity results in a decrease in the apparent stiffness of the fibril and a decrease in the stably-applied force to the fibril. Taken together, these results give novel insights into the combinatorial effects of substrate stiffness and cell contractility on FN fibril assembly.
format	article
author	Seth H Weinberg Navpreet Saini Christopher A Lemmon
author_facet	Seth H Weinberg Navpreet Saini Christopher A Lemmon
author_sort	Seth H Weinberg
title	Effects of substrate stiffness and actin velocity on in silico fibronectin fibril morphometry and mechanics.
title_short	Effects of substrate stiffness and actin velocity on in silico fibronectin fibril morphometry and mechanics.
title_full	Effects of substrate stiffness and actin velocity on in silico fibronectin fibril morphometry and mechanics.
title_fullStr	Effects of substrate stiffness and actin velocity on in silico fibronectin fibril morphometry and mechanics.
title_full_unstemmed	Effects of substrate stiffness and actin velocity on in silico fibronectin fibril morphometry and mechanics.
title_sort	effects of substrate stiffness and actin velocity on in silico fibronectin fibril morphometry and mechanics.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/9e356f9430e047159fdb053b0e944480
work_keys_str_mv	AT sethhweinberg effectsofsubstratestiffnessandactinvelocityoninsilicofibronectinfibrilmorphometryandmechanics AT navpreetsaini effectsofsubstratestiffnessandactinvelocityoninsilicofibronectinfibrilmorphometryandmechanics AT christopheralemmon effectsofsubstratestiffnessandactinvelocityoninsilicofibronectinfibrilmorphometryandmechanics
_version_	1718374963051757568

Effects of substrate stiffness and actin velocity on in silico fibronectin fibril morphometry and mechanics.

Ejemplares similares