Scientists use protein, RNA to make hollow, spherical sacks called
vesicles

Date:
June 23, 2020
Source:
University at Buffalo
Summary:
Using protein and RNA, scientists have created hollow, spherical
sacks known as vesicles. These bubble-like entities -- which form
spontaneously when specific protein and RNA molecules are mixed in
an aqueous buffer solution -- hold potential as biological storage
compartments. They could serve as an alternative to traditional
vesicles that are made from water- insoluble organic compounds
called lipids, researchers say.



FULL STORY ========================================================================== Using protein and RNA, scientists have created hollow, spherical sacks
known as vesicles.


========================================================================== These bubble-like entities -- which form spontaneously when specific
protein and RNA molecules are mixed in an aqueous buffer solution --
hold potential as biological storage compartments. They could serve as
an alternative to traditional vesicles that are made from water-insoluble organic compounds called lipids, researchers say.

"Our discovery has widespread implications, from understanding basic
cell biology to enabling possible biotechnological applications, such as targeted drug delivery or pesticide release," says Priya Banerjee, PhD, assistant professor of physics in the University at Buffalo College of
Arts and Sciences.

"These hollow spheres look and behave like the classical lipid vesicles
that people have been utilizing in bioengineering applications for
many years, with an important exception: They are not made by lipids."
"Because of the hollow structure resembling lipid vesicles, one may
envision a potentially exciting application where protein-RNA vesicles
are dispatched into cells for carrying out rescue missions by releasing biomolecules or changing the local subcellular environment," says
Davit Potoyan, PhD, assistant professor of chemistry at Iowa State
University. "Another reason to be excited is that these vesicles are
formed spontaneously from naturally occurring proteins and nucleic acids,
which may help to avoid issues of toxicity that might be seen in other
polymers designed to mimic lipid vesicles." The findings were published
on June 22 in the Proceedings of the National Academy of Sciences.

Banerjee and Potoyan led the project, along with Ibraheem Alshareedah,
a UB physics PhD student, and Mahdi Muhammad Moosa, PhD, a UB physics postdoctoral scholar, who did the experiments; and Muralikrishna Raju,
PhD, an Iowa State chemistry postdoctoral scholar who carried out
computer simulations.



==========================================================================
To make the micron-sized vesicles, scientists mixed naturally occurring cationic proteins with RNA in an aqueous buffer solution. At some concentrations, the protein and RNA molecules clustered together to
produce liquid droplets, akin to beads of oil floating in water. But at
other concentrations, the protein and RNA instead came together to form
the bubble- like vesicles.

As part of the research, the team also mapped out the conditions under
which each type of structure forms. Experiments and simulations showed
that the protein-RNA complexes coalesce spontaneously and are held
together because of weak electrostatic attraction, repulsive interactions
and chain entropy. A delicate balance of these forces dictates whether
liquid droplets or hollow vesicles will form, the researchers say.

"We argue that there is a tradeoff between these forces," Banerjee
says. "When you have too much repulsion, the protein and RNA molecules
stay separated. But when you balance these intricate forces, you
see a stabilization of these different structures, liquid droplets
or hollow condensates." After discovering the principle of how the
vesicles are formed, the team created similar hollow droplets using other building blocks, such as designed polypeptides and synthetic polymers, demonstrating that the findings could have broad applications.

"We also observed that similar lipid-free vesicles can form with many
proteins and RNA mimetics," Moosa says. "The ability to pick and choose
from a large pool of mimetics will allow customizable biotechnological application of these assemblies." UB has filed a provisional patent application for the lipid-free protein-RNA vesicles and the methods for
making the vesicles.



==========================================================================
The new study resulted from Banerjee's past work on protein-RNA
complexes, which focused on generating liquid droplets from protein and
RNA molecules.

In one experiment, "When we added more RNA to the droplets, immediately
these compartments, these beautiful bubble-like structures, started
forming inside those droplets," Banerjee recalls. "But it wasn't stable,
and it went away in a few minutes." That curious observation led his team
to start investigating how to create the hollow structures and keep them
intact for longer periods, which the new study achieves. The research
on both liquid and hollow droplets could lead to improved understanding
of how similar compartments form spontaneously inside human cells,
Banerjee says.

One intriguing aspect of the study is the formation of vesicular geometry, reminiscent of membranes, arising from protein and RNA molecules, the scientists say. Lipids are well-known building blocks for biological
membranes, but the new study suggests that other possibilities may
exist for creating membrane-like barriers in biological systems that
were previously not known, Banerjee says. Future studies could explore
whether and how cells might use protein-RNA membranes to perform certain biological functions.


========================================================================== Story Source: Materials provided by University_at_Buffalo. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Ibraheem Alshareedah, Mahdi Muhammad Moosa, Muralikrishna Raju,
Davit A.

Potoyan, Priya R. Banerjee. Phase transition of RNA-protein
complexes into ordered hollow condensates. Proceedings
of the National Academy of Sciences, 2020; 201922365 DOI:
10.1073/pnas.1922365117 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/06/200623145312.htm

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