Fluctuations in the Kinetics of Linear Protein Self-Assembly

Biological systems are characterized by compartmentalization from the subcellular to the tissue level, and thus reactions in small volumes are ubiquitous in living systems. Under such conditions, statistical number fluctuations, which are commonly negligible in bulk reactions, can become dominant an...

Full description

Saved in:
Bibliographic Details
Published in:Physical review letters 2016-06, Vol.116 (25), p.258103-258103, Article 258103
Main Authors: Michaels, Thomas C T, Dear, Alexander J, Kirkegaard, Julius B, Saar, Kadi L, Weitz, David A, Knowles, Tuomas P J
Format: Article
Language:English
Subjects:
Agglomeration
Aggregates
Amyloid - chemistry
Fluctuation
Formations
Kinetics
Nucleation
Protein Multimerization
Proteins
Self assembly
Stochastic Processes
Stochasticity
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Biological systems are characterized by compartmentalization from the subcellular to the tissue level, and thus reactions in small volumes are ubiquitous in living systems. Under such conditions, statistical number fluctuations, which are commonly negligible in bulk reactions, can become dominant and lead to stochastic behavior. We present here a stochastic model of protein filament formation in small volumes. We show that two principal regimes emerge for the system behavior, a small fluctuation regime close to bulk behavior and a large fluctuation regime characterized by single rare events. Our analysis shows that in both regimes the reaction lag-time scales inversely with the system volume, unlike in bulk. Finally, we use our stochastic model to connect data from small-volume microdroplet experiments of amyloid formation to bulk aggregation rates, and show that digital analysis of an ensemble of protein aggregation reactions taking place under microconfinement provides an accurate measure of the rate of primary nucleation of protein aggregates, a process that has been challenging to quantify from conventional bulk experiments.
ISSN:0031-9007
1079-7114
DOI:10.1103/PhysRevLett.116.258103