Imperial College London
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ProfessorDarrylOverby

Faculty of Engineering, Department of Bioengineering

Professor of Mechanobiology
 
 
 
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Contact

 

+44 (0)20 7594 6376d.overby

 
 
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Location

 

3.07Bessemer BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@unpublished{Cairoli:2022:10.1101/2022.06.26.497642,
author = {Cairoli, A and Spenlehauer, A and Overby, DR and Lee, CF},
doi = {10.1101/2022.06.26.497642},
title = {Model of inverse bleb growth explains giant vacuole dynamics during cell mechanoadaptation},
url = {http://dx.doi.org/10.1101/2022.06.26.497642},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - UNPB
AB  - <jats:title>Abstract</jats:title><jats:p>Cells can withstand hostile environmental conditions manifest as large mechanical forces such as pressure gradients and/or shear stresses by dynamically changing their shape. Such conditions are realized in the Schlemm’s canal of the eye where endothelial cells that cover the inner vessel wall are subjected to the hydrodynamic pressure gradients exerted by the aqueous humor outflow. These cells form fluid-filled dynamic outpouchings of their basal membrane called<jats:italic>giant vacuoles</jats:italic>. The inverse of giant vacuoles are reminiscent of cellular blebs, extracellular cytoplasmic protrusions triggered by local temporary disruption of the contractile actomyosin cortex. Inverse blebbing has been first observed experimentally during sprouting angiogenesis, but its underlying physical mechanisms are poorly understood. Here, we identify giant vacuole formation as inverse blebbing and formulate a biophysical model of this process. Our model elucidates how cell membrane mechanical properties affect the morphology and dynamics of giant vacuoles and predicts coarsening akin to Ostwald ripening between multiple invaginating vacuoles. Our results are in qualitative agreement with observations from the formation of giant vacuoles during perfusion experiments. Our model not only elucidates the biophysical mechanisms driving inverse blebbing and giant vacuole dynamics, but also identifies universal features of the cellular response to pressure loads that are relevant to many experimental contexts.</jats:p><jats:sec><jats:title>Significance statement</jats:title><jats:p>Human Schlemm’s canal endothelial cells in physiological conditions are subjected to a pressure gradient caused by the flow of aqueous humor in the basal-to-apical direction across the endothelium leading to the formation of cellular outpouchings called giant vacuoles. The physical mechanis
AU  - Cairoli,A
AU  - Spenlehauer,A
AU  - Overby,DR
AU  - Lee,CF
DO  - 10.1101/2022.06.26.497642
PY  - 2022///
TI  - Model of inverse bleb growth explains giant vacuole dynamics during cell mechanoadaptation
UR  - http://dx.doi.org/10.1101/2022.06.26.497642
ER  -
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