A role for nuclear stretching and NPCs changes in the cytoplasmic-nuclear trafficking of YAP: An experimental and numerical modelling approach
Mechanical forces, acting on eukaryotic cells, are responsible for cell shape, cell proliferation, cell polarity, and cell differentiation thanks to two cells abilities known as mechanosensing and mechanotransduction. Mechanosensing consists of the ability of a cell to sense mechanical cues, while m...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2022-06-01
|
Series: | Materials Today Bio |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006422001338 |
_version_ | 1811315959581900800 |
---|---|
author | Stefania Saporito Carlo F. Natale Costantino Menna Paolo Antonio Netti Maurizio Ventre |
author_facet | Stefania Saporito Carlo F. Natale Costantino Menna Paolo Antonio Netti Maurizio Ventre |
author_sort | Stefania Saporito |
collection | DOAJ |
description | Mechanical forces, acting on eukaryotic cells, are responsible for cell shape, cell proliferation, cell polarity, and cell differentiation thanks to two cells abilities known as mechanosensing and mechanotransduction. Mechanosensing consists of the ability of a cell to sense mechanical cues, while mechanotransduction is the capacity of a cell to respond to these signals by translating mechanical stimuli into biochemical ones. These signals propagate from the extracellular matrix to the nucleus with different well known physical connections, but how the mechanical signals are transduced into biochemical ones remains an open challenge. Recent findings showed that the cell-generated forces affect the translocation of transcription factors (TFs) from the cytoplasm to the nucleus. This mechanism is affected by the features of nuclear pore complexes. Owing to the complex patterns of strains and stresses of the nuclear envelope caused by cytoskeletal forces, it is likely that the morphology of NPC changes as cytoskeleton assemblies’ change. This may ultimately affect molecular transport through the nucleus, hence altering cell functions. Among the various TFs, Yes-associated protein (YAP), which is typically involved in cell proliferation, survival, and differentiation, is able to activate specific pathways when entrapped into the cell nucleus. Here, starting from experimental results, we develop a multiscale finite element (FE) model aimed to simulate the macroscopic cell spreading and consequent changes in the cell mechanical behaviour to be related to the NPCs changes and YAP nuclear transport. |
first_indexed | 2024-04-13T11:40:27Z |
format | Article |
id | doaj.art-3ac539f58787458ebf3376add6b0ba9b |
institution | Directory Open Access Journal |
issn | 2590-0064 |
language | English |
last_indexed | 2024-04-13T11:40:27Z |
publishDate | 2022-06-01 |
publisher | Elsevier |
record_format | Article |
series | Materials Today Bio |
spelling | doaj.art-3ac539f58787458ebf3376add6b0ba9b2022-12-22T02:48:19ZengElsevierMaterials Today Bio2590-00642022-06-0115100335A role for nuclear stretching and NPCs changes in the cytoplasmic-nuclear trafficking of YAP: An experimental and numerical modelling approachStefania Saporito0Carlo F. Natale1Costantino Menna2Paolo Antonio Netti3Maurizio Ventre4Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, Italy; Center for Advanced Biomaterials for Healthcare@CRIB, Istituto Italiano Di Tecnologia, ItalyCenter for Advanced Biomaterials for Healthcare@CRIB, Istituto Italiano Di Tecnologia, ItalyDepartment of Structures for Engineering and Architecture, University of Naples Federico II, ItalyDepartment of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, Italy; Center for Advanced Biomaterials for Healthcare@CRIB, Istituto Italiano Di Tecnologia, Italy; Interdisciplinary Research Center on Biomaterials (CRIB), University of Naples Federico II, ItalyDepartment of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, Italy; Center for Advanced Biomaterials for Healthcare@CRIB, Istituto Italiano Di Tecnologia, Italy; Interdisciplinary Research Center on Biomaterials (CRIB), University of Naples Federico II, Italy; Corresponding author. Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, Italy.Mechanical forces, acting on eukaryotic cells, are responsible for cell shape, cell proliferation, cell polarity, and cell differentiation thanks to two cells abilities known as mechanosensing and mechanotransduction. Mechanosensing consists of the ability of a cell to sense mechanical cues, while mechanotransduction is the capacity of a cell to respond to these signals by translating mechanical stimuli into biochemical ones. These signals propagate from the extracellular matrix to the nucleus with different well known physical connections, but how the mechanical signals are transduced into biochemical ones remains an open challenge. Recent findings showed that the cell-generated forces affect the translocation of transcription factors (TFs) from the cytoplasm to the nucleus. This mechanism is affected by the features of nuclear pore complexes. Owing to the complex patterns of strains and stresses of the nuclear envelope caused by cytoskeletal forces, it is likely that the morphology of NPC changes as cytoskeleton assemblies’ change. This may ultimately affect molecular transport through the nucleus, hence altering cell functions. Among the various TFs, Yes-associated protein (YAP), which is typically involved in cell proliferation, survival, and differentiation, is able to activate specific pathways when entrapped into the cell nucleus. Here, starting from experimental results, we develop a multiscale finite element (FE) model aimed to simulate the macroscopic cell spreading and consequent changes in the cell mechanical behaviour to be related to the NPCs changes and YAP nuclear transport.http://www.sciencedirect.com/science/article/pii/S2590006422001338MechanobiologyNuclear poresMicropatterningFinite element modelsStem cells |
spellingShingle | Stefania Saporito Carlo F. Natale Costantino Menna Paolo Antonio Netti Maurizio Ventre A role for nuclear stretching and NPCs changes in the cytoplasmic-nuclear trafficking of YAP: An experimental and numerical modelling approach Materials Today Bio Mechanobiology Nuclear pores Micropatterning Finite element models Stem cells |
title | A role for nuclear stretching and NPCs changes in the cytoplasmic-nuclear trafficking of YAP: An experimental and numerical modelling approach |
title_full | A role for nuclear stretching and NPCs changes in the cytoplasmic-nuclear trafficking of YAP: An experimental and numerical modelling approach |
title_fullStr | A role for nuclear stretching and NPCs changes in the cytoplasmic-nuclear trafficking of YAP: An experimental and numerical modelling approach |
title_full_unstemmed | A role for nuclear stretching and NPCs changes in the cytoplasmic-nuclear trafficking of YAP: An experimental and numerical modelling approach |
title_short | A role for nuclear stretching and NPCs changes in the cytoplasmic-nuclear trafficking of YAP: An experimental and numerical modelling approach |
title_sort | role for nuclear stretching and npcs changes in the cytoplasmic nuclear trafficking of yap an experimental and numerical modelling approach |
topic | Mechanobiology Nuclear pores Micropatterning Finite element models Stem cells |
url | http://www.sciencedirect.com/science/article/pii/S2590006422001338 |
work_keys_str_mv | AT stefaniasaporito arolefornuclearstretchingandnpcschangesinthecytoplasmicnucleartraffickingofyapanexperimentalandnumericalmodellingapproach AT carlofnatale arolefornuclearstretchingandnpcschangesinthecytoplasmicnucleartraffickingofyapanexperimentalandnumericalmodellingapproach AT costantinomenna arolefornuclearstretchingandnpcschangesinthecytoplasmicnucleartraffickingofyapanexperimentalandnumericalmodellingapproach AT paoloantonionetti arolefornuclearstretchingandnpcschangesinthecytoplasmicnucleartraffickingofyapanexperimentalandnumericalmodellingapproach AT maurizioventre arolefornuclearstretchingandnpcschangesinthecytoplasmicnucleartraffickingofyapanexperimentalandnumericalmodellingapproach AT stefaniasaporito rolefornuclearstretchingandnpcschangesinthecytoplasmicnucleartraffickingofyapanexperimentalandnumericalmodellingapproach AT carlofnatale rolefornuclearstretchingandnpcschangesinthecytoplasmicnucleartraffickingofyapanexperimentalandnumericalmodellingapproach AT costantinomenna rolefornuclearstretchingandnpcschangesinthecytoplasmicnucleartraffickingofyapanexperimentalandnumericalmodellingapproach AT paoloantonionetti rolefornuclearstretchingandnpcschangesinthecytoplasmicnucleartraffickingofyapanexperimentalandnumericalmodellingapproach AT maurizioventre rolefornuclearstretchingandnpcschangesinthecytoplasmicnucleartraffickingofyapanexperimentalandnumericalmodellingapproach |