Page 29 - Abacoa Community News - November '24

Abacoa, Page 29

Science On The Cutting Edge from page 28 that cell membrane
lipids, or fats, help
send an electrical
pulse into cells after
experiencing pressure
and force. The
research illuminates
New Study Shows A Role For the path that pain

Cholesterol In Pain Perception signals take from
an injury site to the
brain, and connects
the many biological
players involved.
Im por t a nt l y, t h e Scott Hansen, Ph.D., places a slide designed to record cell
research shows how membrane shear into a super-resolution microscope.
excess cholesterol in Scott Hansen, Ph.D., with his
cell membranes may dSTORM super-resolution pain-relieving responses – so long as there’s no interference
interfere with pain microscope – lessening pain’s severity.
control. Scientists have previously documented the role of a
“Excess cholesterol is a feature in many diseases and mechanical force-sensing enzyme called PLD2 in these
disorders, including diabetes and diseases of aging,” said steps and its ability to activate a pain-relief providing
A cell membrane is illustrated to show the surface in red. Hansen, an associate professor of molecular medicine at potassium channel called TREK-1. Missing was an
Blue objects are proteins, including ion channels, which The Wertheim UF Scripps Institute. “This could be one understanding of how PLD2 and TREK-1 could be
can send electrical impulses into cells. Lipids, or fats, are in explanation for why we see more chronic pain in these activated by the membrane. PLD2 lacked the ability to
yellow. In this cross section, an ion channel associates with groups.” sense tension, the typical way that mechanosensors are
a lipid raft. The function of the lipid structures is regulated The study also adds to mounting evidence that the fatty engaged. Membrane lipids weren’t considered, perhaps
by cholesterol. Mechanical force can deplete the cholesterol molecules that make up cell membranes require structure because they were poorly understood, due to technical
and release the ion channel, changing activity within the to perform their many duties, he added. limitations.
cell. (Illustration by Scott Hansen, Ph.D., The Wertheim UF “Originally, science thought only proteins had “Until recently, the study of these cholesterol-
Scripps Institute.) structures with function,” said Hansen. “It looks like the containing lipid clumps, also called lipid rafts, has been
lipids can be added to that list.” difficult, because they are too small to be seen by a regular
Pressure On Cells Reduces Pain Signals, A cell is made of a fatty exterior membrane encasing a light microscope,” Hansen said.
But Excess Cholesterol Can Interfere, water-based interior. Advanced microscopes and other new Using a super-resolution microscope, Hansen and
Researchers Find technologies are revealing that the cell membrane isn’t simply colleagues documented in several cell types that pressure
a fatty sac, though. Rather, it’s a sophisticated collection of and stretching, or “shear,” caused changes to those fat
When you stub your toe or bump your head, you know sensors, pores, channels, receptors and cholesterol clumps molecules that temporarily altered the cell’s ability to
that rubbing the injury can lessen the ouch. But how? New held in place by precisely arranged fat molecules. activate pain relief. Studies in mice and fruit flies also
research from the lab of Scott B. Hansen, Ph.D., shows “There are two types of fats in the membrane, one is fluid, underscored their findings.
how physical pressure on cells can reduce pain signals, like olive oil, and a second contains cholesterol and is found The research raises interesting questions and
while excessive cholesterol clumps in cell membranes can as tiny, rigid clumps, more like lard,” Hansen said. “It wasn’t opportunities for more study, Hansen said. Many
interfere with that process. known that those fats might play a role in pain signaling.” proteins associate with these lipid structures, including
The research, carried out at The Herbert Wertheim UF To feel pain, first, the injury must be sensed. Second, the proteins involved in Alzheimer’s disease and
Scripps Institute for Biomedical Innovation & Technology, that injury message must convert to a signal that can travel inflammation. Understanding whether inflammation
appears in the scientific journal eLife, Feb. 26, 2024. rapidly through the body and be interpreted by the brain. The affects membrane cholesterol structure, especially in
Hansen and his colleagues’ discoveries are important lipid structure appears to sense the force and convert it into brain cells, may also prove important to understanding
for several reasons. They show for the first time a signal. The signal can then help activate the body’s own the pain-inflammation link.
“New types of non-opioid pain therapeutics are urgently
needed for people who live with chronic pain,” Hansen
said. “Understanding what factors set the threshold for
pain is an important step toward that goal.”
In addition to Hansen, the co-authors of the study,
“Mechanical activation of TWIK-related potassium
channel by nanoscopic movement and rapid second
messenger signaling,” include E. Nicholas Petersen,
Mahmud Arif Pavel, William W. Ja, Samuel S. Hansen, Hao
Wang, Keith R. Murphy, and Zixuan Yuan of The Wertheim
UF Scripps Institute; Heather A. Ferris of the University
of Virginia, Charlottesville; and Erik M. Jorgensen and
Manasa Gudheti of the Howard Hughes Medical Institute
and the University of Utah.
The work was supported by a Director’s New Innovator
Award to Hansen (DP2NS087943), an R21 (AG078845-
01), and R01 (R01NS112534) from the National Institutes
of Health, an R01 to Ja (R01AG045036) from the National
Institute on Aging, and a graduate fellowship to Petersen
from the Joseph B. Scheller & Rita P. Scheller Charitable
Foundation. The JPB Foundation supported the purchase
of a super resolution microscope.

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