Model of inverse bleb growth explains giant vacuole dynamics during cell mechanoadaptation

TL;DR

This paper presents a biophysical model explaining giant vacuole formation in endothelial cells as inverse blebbing, revealing how membrane mechanics influence vacuole dynamics and their response to pressure, with implications for cell mechanoadaptation.

Contribution

The study introduces a novel biophysical model linking inverse blebbing to giant vacuole formation, advancing understanding of cellular responses to mechanical stress.

Findings

Model predicts coarsening of vacuoles similar to Ostwald ripening.

Results align qualitatively with perfusion experiment observations.

Identifies universal features of cellular response to pressure loads.

Abstract

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 \textit{giant vacuoles}. 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.