Imperial College London

ProfessorYuriKorchev

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Professor of Biophysics
 
 
 
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Contact

 

+44 (0)20 3313 3080y.korchev

 
 
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Location

 

BN5, Nanomedicine LabCommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Swiatlowska:2020:10.1039/d0nr02474k,
author = {Swiatlowska, P and Sanchez-Alonso, JL and Mansfield, C and Scaini, D and Korchev, Y and Novak, P and Gorelik, J},
doi = {10.1039/d0nr02474k},
journal = {Nanoscale},
pages = {16315--16329},
title = {Short-term angiotensin II treatment regulates cardiac nanomechanics via microtubule modifications.},
url = {http://dx.doi.org/10.1039/d0nr02474k},
volume = {12},
year = {2020}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Mechanical properties of single myocytes contribute to the whole heart performance, but the measurement of mechanics in living cells at high resolution with minimal force interaction remains challenging. Angiotensin II (AngII) is a peptide hormone that regulates a number of physiological functions, including heart performance. It has also been shown to contribute to cell mechanics by inducing cell stiffening. Using non-contact high-resolution Scanning Ion Conductance Microscopy (SICM), we determine simultaneously cell topography and membrane transverse Young's modulus (YM) by a constant pressure application through a nanopipette. While applying pressure, the vertical position is recorded and a deformation map is generated from which YM can be calculated and corrected for the uneven geometry. High resolution of this method also allows studying specific membrane subdomains, such as Z-grooves and crests. We found that short-term AngII treatment reduces the transversal YM in isolated adult rat cardiomyocytes acting via an AT1 receptor. Blocking either a TGF-β1 receptor or Rho kinase abolishes this effect. Analysis of the cytoskeleton showed that AngII depletes microtubules by decreasing long-lived detyrosinated and acetylated microtubule populations. Interestingly, in the failing cardiomyocytes, which are stiffer than controls, the short-term AngII treatment also reduces the YM, thus normalizing the mechanical state of cells. This suggests that the short-term softening effect of AngII on cardiac cells is opposite to the well-characterized long-term hypertrophic effect. In conclusion, we generate a precise nanoscale indication map of location-specific transverse cortical YM within the cell and this can substantially advance our understanding of cellular mechanics in a physiological environment, for example in isolated cardiac myocytes.
AU - Swiatlowska,P
AU - Sanchez-Alonso,JL
AU - Mansfield,C
AU - Scaini,D
AU - Korchev,Y
AU - Novak,P
AU - Gorelik,J
DO - 10.1039/d0nr02474k
EP - 16329
PY - 2020///
SN - 2040-3364
SP - 16315
TI - Short-term angiotensin II treatment regulates cardiac nanomechanics via microtubule modifications.
T2 - Nanoscale
UR - http://dx.doi.org/10.1039/d0nr02474k
UR - https://www.ncbi.nlm.nih.gov/pubmed/32720664
UR - https://pubs.rsc.org/en/content/articlelanding/2020/NR/D0NR02474K#!divAbstract
UR - http://hdl.handle.net/10044/1/81672
VL - 12
ER -