Two amino acids are the Marie Kondo of molecular liquid phase separation
The discovery advances a novel area of cell biology and provides
important clues about causes of cellular disfunction and disease

Date:
September 15, 2020
Source:
Advanced Science Research Center, GC/CUNY
Summary:
Biologists have identified unique roles for the amino acids arginine
and lysine in contributing to molecule liquid phase properties
and their regulation.



FULL STORY ==========================================================================
The last several years have brought mounting evidence that the molecules
inside our cells can self-organize into liquid droplets that merge
and separate like oil in water in order to facilitate various cellular activities. Now, a team of biologists at the Advanced Science Research
Center at The Graduate Center, CUNY (CUNY ASRC) have identified unique
roles for the amino acids arginine and lysine in contributing to liquid
phase properties and their regulation. Their findings are available
today online in Nature Communications.


========================================================================== Known as liquid-liquid phase separation, the process allows some molecules within a cell to cloister themselves into membraneless organelles in order
to carry out certain duties without interruption from other molecules. The mechanism can also allow molecules to create multiphase droplets that
resemble, say, a drop of honey inside a drop of oil surrounded by water
in order to carry out sophisticated jobs.

"This is a really exciting new research area because it uncovers a
core biological function that, when gone awry, may be at the root of
disease, particularly neurodegeneration as in ALS or Alzheimer's," said principal investigator and Graduate Center, CUNY Biochemistry Professor
Shana Elbaum- Garfinkle, whose lab at the CUNY ASRC Structural Biology Initiative conducted the study. "With an understanding of how individual
amino acids contribute to phase behavior, we can begin to investigate
what's going wrong in liquid phase separation that may interfere with
normal biological function and potentially design therapies that can
modulate the process." Researchers have suspected for a while that
arginine and lysine -- two of the 20 amino acids that make up all proteins
-- were responsible for regulating liquid phase separation, but they
weren't certain how each contributed to phase behavior and to creating the differing viscosities that cloister molecules into separate communities.

"Arginine and lysine are very similar amino acids in terms of both being positively charged, but they differ in terms of binding capability. We
were really curious to understand what effect this difference would
have on the material properties, such as viscosity or fluidity, of the
droplets they form," said Rachel Fisher, the paper's first author and a
postdoc in Elbaum- Garfinkle's lab. "We also wanted to know how these differences manifest themselves when the arginine and lysine systems
are combined. Will the droplets coexist? When we saw they did, we then
wanted to understand how we could modulate this multi-phase behavior."
To answer their questions, Elbaum-Garfinkle's team used a technique
called microrheology -- whereby tiny tracers are used to probe material structures - - to track and investigate the properties of arginine
and lysine droplets. They found that arginine-rich droplets were over
100 times more viscous than lysine- rich droplets, comparable to the
difference between a thick syrup or ketchup and oil. The viscosity
differences are significant enough that if lysine and arginine polymers
are combined, they don't mix. Instead, they create multi- phase droplets
that sit within one another like Dutch nesting dolls.

Additionally, arginine has such strong binding properties that under
some conditions it can compete with lysine and replace or dissolve
lysine droplets.

The researchers further identified ways to tune the balance between
competition and coexistence of the two phases. The results present a
novel mechanism for designing, controlling or intervening in molecular
liquid phases.


========================================================================== Story Source: Materials provided by
Advanced_Science_Research_Center,_GC/CUNY. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Rachel S. Fisher, Shana Elbaum-Garfinkle. Tunable multiphase
dynamics of
arginine and lysine liquid condensates. Nature Communications,
2020; 11 (1) DOI: 10.1038/s41467-020-18224-y ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200915090114.htm

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