Cluster coarsening on drops exhibits strong and sudden size-selectivity.

Aidan I Brown,Andrew D Rutenberg

doi:10.1039/c5sm00284b

Abstract

Autophagy, an important process for degradation of cellular components, requires the targeting of autophagy receptor proteins to potential substrates. Receptor proteins have been observed to form clusters on membranes. To understand how receptor clusters might affect autophagy selectivity, we model cluster coarsening on a polydisperse collection of spherical drop-like substrates. Our model receptor corresponds to NBR1, which supports peroxisome autophagy. We recover dynamical scaling of cluster sizes, but find that changing the drop size distribution changes the cluster-size scaling distribution. The magnitude of this effect is similar to how changing the spatial-dimension affects scaling in bulk systems. We also observe a sudden onset of size-selection of the remaining drops with clusters, due to clusters evaporating from smaller drops and growing on larger drops. This coarsening-driven size selection provides a physical mechanism for autophagy selectivity, and may explain reports of size selection during peroxisome degradation.

Highlights

Domain coarsening describes multiple clusters growing in average size but decreasing in number, due to the conserved amount of constituents in the system.[1]
We expect that drop-size distributions with compact support will have the same cluster size scaling functions as the uniform distribution, while drop-size distributions with tails may have scaling functions that vary with the drop-size distribution width
We have explored a physical mechanism of size-selection exploiting cluster coarsening on drops

Summary

Introduction

Domain coarsening describes multiple clusters growing in average size but decreasing in number, due to the conserved amount of constituents in the system.[1]. Autophagy is an important system for the degradation of large cellular substrates,[5] including protein aggregates, organelles, and pathogenic bacteria. While autophagy was initially described as a non-selective ‘‘self-eating’’ degradation pathway,[6] it is capable of selective substrate degradation. Autophagy substrates are directed to the lysosome for degradation in a multi-stage process that requires receptor protein attachment, and selectivity appears to be mediated by a growing list of autophagy receptor proteins.[7] there is a developing understanding of how different receptor proteins select distinct organelles for autophagy,[6,7] e.g. peroxisomes vs mitochondria, there has been little investigation of how individual organelles are selected from among a subcellular population. What physical cues could lead to the selection of individual organelles?

Objectives

Results

Discussion

Conclusion