An adapted particle swarm optimization algorithm as a model for exploring premyofibril formation.

William Sherman,Anna Grosberg

doi:10.1063/1.5145010

Abstract

While the fundamental steps outlining myofibril formation share a similar scheme for different cell and species types, various granular details involved in the development of a functional contractile muscle are not well understood. Many studies of myofibrillogenesis focus on the protein interactions that are involved in myofibril maturation with the assumption that there is a fully formed premyofibril at the start of the process. However, there is little known regarding how the premyofibril is initially constructed. Fortunately, the protein α-actinin, which has been consistently identified throughout the maturation process, is found in premyofibrils as punctate aggregates known as z-bodies. We propose a theoretical model based on the particle swarm optimization algorithm that can explore how these α-actinin clusters form into the patterns observed experimentally. Our algorithm can produce different pattern configurations by manipulating specific parameters that can be related to α-actinin mobility and binding affinity. These patterns, which vary experimentally according to species and muscle cell type, speak to the versatility of α-actinin and demonstrate how its behavior may be altered through interactions with various regulatory, signaling, and metabolic proteins. The results of our simulations invite speculation that premyofibrils can be influenced toward developing different patterns by altering the behavior of individual α-actinin molecules, which may be linked to key differences present in different cell types.

Highlights

Across species, molecular interactions cause myofibrils to transmit forces both within and between neighboring myocytes with extreme precision, allowing for coordinated muscular contractions
There are conflicting reports regarding the dynamic movement of α-actinin in the early stages of myofibril formation that coincide with the muscle cell type
Focus was placed on the ideal distance parameter rm, which could coincide with the muscle cell type, and the cluster searching distance dth, which defined the necessary spatial distance for cluster recruitment to be considered

Summary

Introduction

Molecular interactions cause myofibrils to transmit forces both within and between neighboring myocytes with extreme precision, allowing for coordinated muscular contractions. This force transmission comes about because of synchronizing interactions across the highly ordered myofibril structure consisting of thick and thin filaments with α-actinin forming the mechanical link between thin actin filaments.. Stage myofibrils, termed premyofibrils, can be identified by the clusters of α-actinin distributed throughout their length.2,3 Following their formation, the spacing between these punctate α-actinin aggregates, designated as z-bodies, increases leading to α-actinin registration and lateral fusion amongst neighboring premyofibrils. This creates the striated patterns found on mature myofibrils referred to as z-lines.. This creates the striated patterns found on mature myofibrils referred to as z-lines. These patterns have been observed in various cell types across multiple species including cardiac cells, skeletal muscle cells, and flight muscle cells.

Methods

Results

Conclusion