Emory Study Finds Muscle Actin Filaments Can Grow From an End Once Thought Impossible

Muscle cells face a persistent puzzle: the actin filaments that let muscles contract must stay precisely the right length, yet they continually age and need rebuilding. Biophysicists at Emory University have now identified a mechanism that helps explain how, showing for the first time that actin can grow from an end long thought unable to support this kind of assembly. The findings, published in Nature Communications, could improve understanding of muscle disorders such as dilated cardiomyopathy, a leading cause of heart failure.

"We've made a fundamental advance in understanding how the cellular cytoskeleton is assembled, especially in muscle cells," said Shashank Shekhar, an Emory physics professor and the study's senior author. Each actin filament has two ends — a pointed, or minus, end and a barbed, or plus, end — and the standard model used for 40 years held that filaments grow only at the plus end while losing units from the minus end, a process called treadmilling.

In muscle cells, that model runs into a problem: the plus end of actin filaments inside the muscle's contractile units, called sarcomeres, is capped by a protein that blocks new material from attaching, yet filaments still need replacing as their proteins age. The Emory team found that leiomodin 2 instead lets actin filaments grow from the minus end — a mechanism "previously thought impossible," Shekhar said.

"We also provide a molecular explanation for how defects in leiomodin can disrupt the assembly of the contractile machinery of the heart," said Sudipta Biswas, an Emory PhD candidate and the study's first author. A genetic mutation affecting leiomodin has been linked to dilated cardiomyopathy, which progressively weakens heart muscle and reduces its ability to pump blood.

Within a sarcomere, actin filaments slide past myosin, shortening the structure like pulling a drawstring while the filaments themselves keep the same length. "From birth to death, the length of the actin filaments in muscle cells stays the same," Shekhar said. "It's very tightly controlled."