ScienceDaily/Brown University: Computer models provide new understanding of sickle cell disease

ScienceDaily

Science News
from research organizations

Computer models provide new understanding of sickle cell disease

Date:
    July 28, 2017
Source:
    Brown University
Summary:
    Simulations developed by mathematicians provide new details of how sickle cell disease manifests inside red blood cells, which could help in developing new treatments.
Share:

FULL STORY
A new modeling technique enables researchers to see what happens inside red blood cells affected by sickle cell disease.
Credit: Karniadakis lab / Brown University

Computer models developed by Brown University mathematicians show new details of what happens inside a red blood cell affected by sickle cell disease. The researchers said they hope their models, described in an article in the Biophysical Journal, will help in assessing drug strategies to combat the genetic blood disorder, which affects millions of people worldwide.

Sickle cell disease affects hemoglobin, molecules within red blood cells responsible for transporting oxygen. In normal red blood cells, hemoglobin is dispersed evenly throughout the cell. In sickle red blood cells, mutated hemoglobin can polymerize when deprived of oxygen, assembling themselves into long polymer fibers that push against the membranes of the cells, forcing them out of shape. The stiff, ill-shaped cells can become lodged in small capillaries throughout the body, leading to painful episodes known as sickle cell crisis.

"The goal of our work is to model both how these sickle hemoglobin fibers form as well as the mechanical properties of those fibers," said Lu Lu, a Ph.D. student in Brown Division of Applied Mathematics and the study's lead author. "There had been separate models for each of these things individually developed by us, but this brings those together into one comprehensive model."

The model uses detailed biomechanical data on how sickle hemoglobin molecules behave and bind with each other to simulate the assembly of a polymer fiber. Prior to this work, the problem had been that as the fiber grows, so does the amount of data the model must crunch. Modeling an entire polymer fiber at cellular scale using the details of each molecule was simply too computationally expensive.

"Even the world's fastest supercomputers wouldn't be able to handle it," said George Karniadakis, professor of applied math at Brown and the paper's senior author. "There's just too much happening and no way to capture it all computationally. That's what we were able to overcome with this work."

The researchers' solution was to apply what they call a mesoscopic adaptive resolution scheme or MARS. The MARS model calculates the detailed dynamics of each individual hemoglobin molecule only at the each end of polymer fibers, where new molecules are being recruited into the fiber. Once four layers of a fiber have been established, the model automatically dials back the resolution at which it represents that section. The model retains the important information about how the fiber behaves mechanically, but glosses over the fine details of each constituent molecule.

"By eliminating the fine details where we don't need them, we develop a model that can simulate this whole process and its effects on a red blood cell," Karniadakis said.

Using the new MARS simulations, the researchers were able to show how different configurations of growing polymer fibers are able to produce cells with different shapes. Though the disease gets its name because it causes many red blood cells take on a sickle-like shape, there are actually a variety of abnormal cell shapes present. This new modeling approach showed new details about how different fiber structures inside the cell produce different cell shapes.

"We are able to produce a polymerization profile for each of the cell types associated with the disease," Karniadakis said. "Now the goal is to use these models to look for ways of preventing the disease onset."

There are only two drugs on the market that has been approved by the FDA for treating sickle cell, Karniadakis says. One of them, called hydroxyurea, is thought to work by boosting the amount of fetal hemoglobin -- the kind of hemoglobin that babies are born with -- in a patient's blood. Fetal hemoglobin is resistant to polymerization and, when present in sufficient quantity, is thought to disrupt the polymerization of sickle cell hemoglobin.

Using these new models, Karniadakis and his colleagues can now run simulations that include fetal hemoglobin. Those simulations could help to confirm that fetal hemoglobin does indeed disrupt polymerization, as well as help to establish how much fetal hemoglobin is necessary. That could help in establishing better dosage guidelines or in developing new and more effective drugs, the researchers say.

"The models give us a way to do preliminary testing on new approaches to stopping this disease," Karniadakis said. "Now that we can simulate the entire polymerization process, we think the models will be much more useful."

Story Source:

Materials provided by Brown University. Note: Content may be edited for style and length.

Journal Reference:

    Lu Lu, He Li, Xin Bian, Xuejin Li, George Em Karniadakis. Mesoscopic Adaptive Resolution Scheme toward Understanding of Interactions between Sickle Cell Fibers. Biophysical Journal, 2017; 113 (1): 48 DOI: 10.1016/j.bpj.2017.05.050

Cite This Page:

    MLA
    APA
    Chicago

Brown University. "Computer models provide new understanding of sickle cell disease." ScienceDaily. ScienceDaily, 28 July 2017. <www.sciencedaily.com/releases/2017/07/170728153954.htm>.

RELATED STORIES
Custom Blood Cells Engineered by Researchers
Mar. 10, 2015 — Researchers have successfully corrected a genetic error in stem cells from patients with sickle cell disease, and then used those cells to grow mature red blood cells, they report. The study ... read more
Developing First Comprehensive Guidelines for Management of Sickle Cell Disease
Sep. 9, 2014 — The National Heart, Lung, and Blood Institute has released the first comprehensive, evidence-based guidelines for management of sickle cell disease from birth to end of life. Sickle cell anemia is ... read more
Regular Blood Transfusions Can Reduce Repeat Strokes in Children With Sickle Cell Disease
Aug. 20, 2014 — Regular blood transfusion therapy significantly reduces the recurrence of silent strokes and strokes in children with sickle cell anemia who have had pre-existing silent strokes, according to study ... read more
Computer Models Shed New Light on Sickle Cell Crisis
June 24, 2013 — Sickle cell crisis, a painful blood blockage common in people with sickle cell disease, isn't just about sickle-shaped red blood cells that block capillaries. According to new computer models, a ... read more
Most Popular
this week
HEALTH & MEDICINE
In Saliva, Clues to a 'Ghost' Species of Ancient Human
Brain Cells Found to Control Aging
How Physical Exercise Prevents Dementia
Study Finds 90 Percent of American Men Overfat
MIND & BRAIN
'Residual Echo' of Ancient Humans in Scans May Hold Clues to Mental Disorders
In Baby's Dirty Diapers, the Clues to Baby's Brain Development
Do All People Experience Similar Near-Death-Experiences?
Using Money to Buy Time Linked to Increased Happiness
LIVING & WELL
Eating at 'Wrong Time' Affects Body Weight, Circadian Rhythms
Rush Hour Pollution May Be More Dangerous Than You Think
Alcohol Boosts Recall of Earlier Learning, Study Suggests
Mediterranean-Style Diets Linked to Better Brain Function in Older Adults
Strange & Offbeat

HEALTH & MEDICINE
Sticky When Wet: Strong Adhesive for Wound Healing
Diet Choice, Reproduction of Fruit Flies Affected by Gut Bacteria
Anyone for Crispy Jellyfish?
New DNA Sunscreen Gets Better the Longer You Wear It
MIND & BRAIN
To Pick a Great Gift, It's Better to Give AND Receive
'Are We There Yet?' Explaining ADHD Science to Children
Do All People Experience Similar Near-Death-Experiences?
Talking to Yourself in the Third Person Can Help You Control Emotions
LIVING & WELL
Alcohol Boosts Recall of Earlier Learning, Study Suggests
Neuroticism May Postpone Death for Some
Meaningless Accelerating Scores Yield Better Performance
Social Status of Listener Alters Our Voice

    SD

    Health
    Tech
    Enviro
    Society
    Quirky

A-AA+
Free Subscriptions

Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

    Email Newsletters
    RSS Feeds

Follow Us

Keep up to date with the latest news from ScienceDaily via social networks:

    Facebook
    Twitter
    Google+
    LinkedIn

Mobile Apps

Get the latest news from ScienceDaily via our free mobile apps, available for download on the following platforms:

    iPhone/iPad
    Android

Have Feedback?

Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?

    Leave Feedback
    Contact Us

About This Site  |  Editorial Staff  |  Awards & Reviews  |  Contribute  |  Advertise  |  Privacy Policy  |  Terms of Use
Copyright 2017 ScienceDaily or by third parties, where indicated. All rights controlled by their respective owners.
Content on this website is for information only. It is not intended to provide medical or other professional advice.
Views expressed here do not necessarily reflect those of ScienceDaily, its staff, its contributors, or its partners.
99