Local Changes in Protein Filament Properties Drive Large-Scale Membrane Transformations Involved in Endosome Tethering and Fusion

TL;DR

This study reveals how local changes in protein filament flexibility on endosomal membranes can induce large-scale membrane fluidization, facilitating vesicle fusion crucial for cellular function, through a novel polymer field-theoretic model.

Contribution

The paper introduces a polymer field-theoretic model to predict how filament alignment affects membrane elasticity and fusion, highlighting a new mechanism for cellular membrane transformation.

Findings

Filament alignment increases membrane elasticity over 20-fold.

Rigid-to-flexible filament transformation triggers membrane fluidization.

Membrane flexibility modulation facilitates vesicle fusion.

Abstract

Large-scale cellular transformations are triggered by subtle physical and structural changes in individual biomacromolecular and membrane components. A prototypical example of such an event is the orchestrated fusion of membranes within an endosome that enables transport of cargo and processing of biochemical moieties. In this work, we demonstrate how protein filaments on the endosomal membrane surface can leverage a rigid-to-flexible transformation to elicit a large-scale change in membrane flexibility to enable membrane fusion. We develop a polymer field-theoretic model that captures molecular alignment arising from nematic interactions with varying surface density and fraction of flexible filaments, which are biologically controlled within the endosomal membrane. We then predict the collective elasticity of the filament brush in response to changes in the filament alignment, predicting a greater than 20-fold increase of the effective membrane elasticity over the bare membrane elasticity that is triggered by filament alignment. These results show that the endosome can modulate the filament properties to orchestrate membrane fluidization that facilitates vesicle fusion, providing an example of how active processes that modulate local molecular properties can result in large-scale transformations that are essential to cellular survival.