Mechanical regulation of endocytosis by protein droplet capillary forces
- 1Leibniz-Institut fuer Polymerforschung
Abstract
Clathrin-mediated endocytosis (CME) is the primary pathway for internalization of extracellular and membrane cargo in eukaryotic cells. It is characterized by a patch of the plasma membrane invaginating and pinching off to generate a cytoplasmic vesicle. Recently, experimental evidence has begun to accumulate in support of proteins assembling into liquid-like condensates at nascent CME sites, but potential functional consequences are not understood. Given that condensate capillary forces can influence membrane bending, we constructed complementary analytical and numerical model systems to probe the mechanical influence of a protein droplet on endocytosis. Model evaluations and analysis reveal that a droplet can regulate the progression of endocytosis by stalling invagination until the droplet grows past a threshold size. After the droplet-mediated brake is released, the droplet provides a force that can drive the membrane bud toward scission. Thus, we propose a ``mechanical timer'' mechanism as a function for protein phase separation in cellular membrane trafficking.
Related
- Targeted protein degradation via chimeric antigen receptor (CAR)-mediated antigen endocytosis in T cells.
- P2Y receptor-mediated regulation of lipolysis, lipid droplet dynamics, and energy metabolism in podocytes
- Identification of TMEM263 as an ER-resident protein that controls early stages of lipid droplet biogenesis
- Cell-sized droplet interfaces reorganize protein secondary structures through confinement-enhanced membrane interactions
- Mechanical regulation of LINC complex function: structural basis, physiological roles, and disease mechanisms in transnuclear mechanotransduction
BibTeX
@misc{ferrin2026mechanical,
title = {{Mechanical regulation of endocytosis by protein droplet capillary forces}},
author = {M. A. Ferrin and D. Mokbel and M. Mokbel and D. G. Drubin and S. Aland and F. Julicher and T. S. Harmon},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.27.754800},
url = {https://www.biorxiv.org/content/10.64898/2026.09.27.754800v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Mechanical regulation of endocytosis by protein droplet capillary forces
AU - M. A. Ferrin
AU - D. Mokbel
AU - M. Mokbel
AU - D. G. Drubin
AU - S. Aland
AU - F. Julicher
AU - T. S. Harmon
PY - 2026
DA - 2026/09/27
PB - bioRxiv
DO - 10.64898/2026.09.27.754800
UR - https://www.biorxiv.org/content/10.64898/2026.09.27.754800v1
AB - Clathrin-mediated endocytosis (CME) is the primary pathway for internalization of extracellular and membrane cargo in eukaryotic cells. It is characterized by a patch of the plasma membrane invaginating and pinching off to generate a cytoplasmic vesicle. Recently, experimental evidence has begun to accumulate in support of proteins assembling into liquid-like condensates at nascent CME sites, but potential functional consequences are not understood. Given that condensate capillary forces can influence membrane bending, we constructed complementary analytical and numerical model systems to probe the mechanical influence of a protein droplet on endocytosis. Model evaluations and analysis reveal that a droplet can regulate the progression of endocytosis by stalling invagination until the droplet grows past a threshold size. After the droplet-mediated brake is released, the droplet provides a force that can drive the membrane bud toward scission. Thus, we propose a ``mechanical timer'' mechanism as a function for protein phase separation in cellular membrane trafficking.
ER -