Biophysicists announced on July 29 that they have uncovered how muscles form at the molecular level and maintain their function, a discovery published in Nature Communications that may inform treatments for muscle diseases such as dilated cardiomyopathy.
"We've made a fundamental advance in understanding how the cellular cytoskeleton is assembled, especially in muscle cells," said Shashank Shekhar, assistant professor of physics at Emory University and senior author of the study.
The research challenges a four-decade-old model explaining how filaments of actin—a protein essential to cellular movement—form and maintain their length. "Our work challenges a long-standing paradigm by uncovering a new mechanism, previously thought impossible, by which the protein leimodin builds actin filaments in muscle," Shekhar said.
Sudipta Biswas, an Emory PhD candidate and first author of the paper, said, "We also provide a molecular explanation for how defects in leimodin can disrupt the assembly of the contractile machinery of the heart." A genetic mutation in leimodin is linked to dilated cardiomyopathy, which weakens heart muscles and impairs blood pumping ability.
The study focused on leiomodin 2 found near pointed ends of actin filaments in cardiac muscle cells. Using microfluidic-assisted total internal reflection fluorescence microscopy (mf-TIRF), researchers observed that actin filaments grow from their pointed ends when anchored by leiomodin. "We provided the first direct molecular evidence that actin filaments grow from their pointed ends," Biswas said. "We proved those who thought this wasn't possible wrong."
Co-authors include Tania Larrinaga (University of Arizona; Icahn School of Medicine), Sandeep Choubey (Institute of Mathematical Sciences; Homi Bhabha National Institute), and Carol Gregorio (Icahn School). The research was supported by grants from federal agencies.
