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Mysterious cellular droplets come into focus

Increase font size  Decrease font size Date:2020-09-14   Views:19

The world inside the human cell has grown a bit more interesting in recent years as the role of a new biological structure became clearer.

It was long believed that most important operations in the cell occur within organelles. "They're there to do certain functions. For instance, mitochondria generate the energy that everything runs on," explained Aleksei Aksimentiev, a professor of physics at the University of Illinois at Urbana-Champaign. "What is common to all of them is that they're surrounded by a lipid membrane. What people recently discovered is there are organelles that don't have lipid bilayers. They assemble spontaneously in the form of droplets. And those organelles have particular functions."

In recent years, with improved imaging capabilities, the roles, occurrence, and behavior of these membrane-less organelles have become clearer. In 2017 they were given a name: biological condensates. They are thought to play a role in DNA repair and aging, and researchers believe a number of neurological diseases are related to the condensate not working properly, including Amyotrophic lateral sclerosis, or ALS, where nerve cells break down, leading to loss of muscular function.

"Let's say you have DNA and it suddenly has a break. It's usually a really bad thing, because it cannot replicate, but there's a machinery that will come and repair it," he explained. "A bubble of condensate forms that miraculously attracts only the molecules that are required to repair the DNA. There are all kinds of different condensates and they all recruit the right molecules somehow."

How do these membrane-less organelles spontaneously form? And how do they recruit other molecules to help them?

The physics of this process appears similar to phase separation, like how oil and water spontaneously form droplets in the right conditions, but with some differences. In normal phase separation, temperature usually motivates the separation. In biology, it is a change in concentrations.

"We don't know exactly how it works," Aksimentiev said. "I'm specifically interested in how this recruitment happens, and how molecules recognize other molecules."

Aksimentiev is using the Frontera supercomputer at the Texas Advanced Computing Center (TACC), one of the fastest in the world, to better understand this process. Over the last decade, he and others developed the tools and methods to explore the behavior of biological systems at the atomic level using molecular dynamics simulations.

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