On top of the meaning and mystery that humans heap on the heart, it is first and foremost, a muscle. And one that beats about once a second for a person’s entire life, with no rest. Given its vital importance, it’s ironic researchers have only recently made direct observations of its subcellular parts in motion.

Now, using new high-resolution microscopy, a team from thePerelman School of Medicine and the School of Engineering and Applied Science at the University of Pennsylvania found that molecular struts called microtubules (MT) interact with the heart’s contractile machinery to provide mechanical resistance for the beating of the heart.  Their findings, which could have implications for better understanding how microtubules affect the mechanics of the beating heart, and what happens when this goes awry, are published this week in Science.

Microtubules of the cell’s inner support system have diverse structural and signaling roles in heart muscle cells. Alterations in this microtubule network have been suggested to contribute to heart disease, but just how microtubules behave in the beating heart is poorly understood.

Direct observation of MTs during contraction is the most straightforward way to shed light on their contributions to heart function. The team observed temporal and spatial changes in MT shape during heart contraction. In addition, recent studies suggest that chemical changes to the MTs, called detyrosination (the removal of a tyrosine chemical group), regulate mechanotransduction, but it was unclear how.

Under Pressure

“We asked whether detyrosination alters how microtubules respond to changing physical pressure each time the heart contracts and relaxes,” said senior author Ben Prosser, PhD, an assistant professor of Physiology. “To answer these questions we used advanced imaging techniques to explore microtubule behavior in beating heart muscle cells from rodents.”

Under the microscope, cardiac muscle looks like interconnected bundles, termed myocytes. Heart myocytes are narrower and much shorter than skeletal muscle cells, with many mitochondria that produce the energy needed for all of that beating over a lifetime. “Heart muscle tissue is highly organized and that’s why it’s such an efficient machine,” Prosser explained.

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