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...

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Main Authors: Stefania Saporito, Carlo F. Natale, Costantino Menna, Paolo Antonio Netti, Maurizio Ventre
Format: Article
Language:English
Published: Elsevier 2022-06-01
Series:Materials Today Bio
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2590006422001338
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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.
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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
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