Early tension regulation coupled to surface myomerger is necessary for the primary fusion of C2C12 myoblasts

Here, we study the time-dependent regulation of fluctuation–tension during myogenesis and the role of the fusogen, myomerger. We measure nanometric height fluctuations of the basal membrane of C2C12 cells after triggering differentiation. Fusion of cells increases fluctuation–tension but prefers a t...

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Main Authors: Madhura Chakraborty, Athul Sivan, Arikta Biswas, Bidisha Sinha
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-10-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2022.976715/full
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author Madhura Chakraborty
Athul Sivan
Arikta Biswas
Bidisha Sinha
author_facet Madhura Chakraborty
Athul Sivan
Arikta Biswas
Bidisha Sinha
author_sort Madhura Chakraborty
collection DOAJ
description Here, we study the time-dependent regulation of fluctuation–tension during myogenesis and the role of the fusogen, myomerger. We measure nanometric height fluctuations of the basal membrane of C2C12 cells after triggering differentiation. Fusion of cells increases fluctuation–tension but prefers a transient lowering of tension (at ∼2–24 h). Cells fail to fuse if early tension is continuously enhanced by methyl-β-cyclodextrin (MβCD). Perturbing tension regulation also reduces fusion. During this pre-fusion window, cells that finally differentiate usually display lower tension than other non-fusing cells, validating early tension states to be linked to fate decision. Early tension reduction is accompanied by low but gradually increasing level of the surface myomerger. Locally too, regions with higher myomerger intensity display lower tension. However, this negative correlation is lost in the early phase by MβCD-based cholesterol depletion or later as differentiation progresses. We find that with tension and surface-myomerger’s enrichment under these conditions, myomerger clusters become pronouncedly diffused. We, therefore, propose that low tension aided by clustered surface-myomerger at the early phase is crucial for fusion and can be disrupted by cholesterol-reducing molecules, implying the potential to affect muscle health.
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spelling doaj.art-1d17813fe5004838aa057919bc16e2ce2022-12-22T03:30:58ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-10-011310.3389/fphys.2022.976715976715Early tension regulation coupled to surface myomerger is necessary for the primary fusion of C2C12 myoblastsMadhura ChakrabortyAthul SivanArikta BiswasBidisha SinhaHere, we study the time-dependent regulation of fluctuation–tension during myogenesis and the role of the fusogen, myomerger. We measure nanometric height fluctuations of the basal membrane of C2C12 cells after triggering differentiation. Fusion of cells increases fluctuation–tension but prefers a transient lowering of tension (at ∼2–24 h). Cells fail to fuse if early tension is continuously enhanced by methyl-β-cyclodextrin (MβCD). Perturbing tension regulation also reduces fusion. During this pre-fusion window, cells that finally differentiate usually display lower tension than other non-fusing cells, validating early tension states to be linked to fate decision. Early tension reduction is accompanied by low but gradually increasing level of the surface myomerger. Locally too, regions with higher myomerger intensity display lower tension. However, this negative correlation is lost in the early phase by MβCD-based cholesterol depletion or later as differentiation progresses. We find that with tension and surface-myomerger’s enrichment under these conditions, myomerger clusters become pronouncedly diffused. We, therefore, propose that low tension aided by clustered surface-myomerger at the early phase is crucial for fusion and can be disrupted by cholesterol-reducing molecules, implying the potential to affect muscle health.https://www.frontiersin.org/articles/10.3389/fphys.2022.976715/fullmyoblast fusionmembrane tensionmembrane fluctuationsmyomergercholesterol
spellingShingle Madhura Chakraborty
Athul Sivan
Arikta Biswas
Bidisha Sinha
Early tension regulation coupled to surface myomerger is necessary for the primary fusion of C2C12 myoblasts
Frontiers in Physiology
myoblast fusion
membrane tension
membrane fluctuations
myomerger
cholesterol
title Early tension regulation coupled to surface myomerger is necessary for the primary fusion of C2C12 myoblasts
title_full Early tension regulation coupled to surface myomerger is necessary for the primary fusion of C2C12 myoblasts
title_fullStr Early tension regulation coupled to surface myomerger is necessary for the primary fusion of C2C12 myoblasts
title_full_unstemmed Early tension regulation coupled to surface myomerger is necessary for the primary fusion of C2C12 myoblasts
title_short Early tension regulation coupled to surface myomerger is necessary for the primary fusion of C2C12 myoblasts
title_sort early tension regulation coupled to surface myomerger is necessary for the primary fusion of c2c12 myoblasts
topic myoblast fusion
membrane tension
membrane fluctuations
myomerger
cholesterol
url https://www.frontiersin.org/articles/10.3389/fphys.2022.976715/full
work_keys_str_mv AT madhurachakraborty earlytensionregulationcoupledtosurfacemyomergerisnecessaryfortheprimaryfusionofc2c12myoblasts
AT athulsivan earlytensionregulationcoupledtosurfacemyomergerisnecessaryfortheprimaryfusionofc2c12myoblasts
AT ariktabiswas earlytensionregulationcoupledtosurfacemyomergerisnecessaryfortheprimaryfusionofc2c12myoblasts
AT bidishasinha earlytensionregulationcoupledtosurfacemyomergerisnecessaryfortheprimaryfusionofc2c12myoblasts