Source abstract
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.
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Affiliations
Center for Complex Biological Systems, University of California Irvine 1 , Irvine, California 92697-2280, USA
Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California Irvine 2 , Irvine, California 92697-2730, USA
Department of Biomedical Engineering, University of California Irvine 3 , Irvine, California 92697-2715, USA
Department of Chemical and Biomolecular Engineering, University of California Irvine 4 , Irvine, California 92697-2580, USA
NSF-Simons Center for Multiscale Cell Fate Research, University of California Irvine 5 , Irvine, California 92697, USA
Funding
Simons Foundation · Training Program in Cardiovascular Applied Research and Entrepreneurship · Division of Mathematical Sciences