Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

Mechanical Forces Control Assembly and Disassembly of a Key Cell Protein

Published: Tuesday, April 02, 2013
Last Updated: Tuesday, April 02, 2013
Bookmark and Share
Researchers have for the first time demonstrated that mechanical forces can control the depolymerization of actin.

The research suggests that forces applied both externally and internally may play a much larger role than previously believed in regulating a range of processes inside cells.

Using atomic force microscopy (AFM) force-clamp experiments, the research found that tensile force regulates the kinetics of actin dissociation by prolonging the lifetimes of bonds at low force range, and by shortening bond lifetimes beyond a force threshold. The research also identified a possible molecular basis for the bonds that form when mechanical forces create new interactions between subunits of actin.

Found in the cytoskeleton of nearly all cells, actin forms dynamic microfilaments that provide structure and sustain forces. A cell’s ability to assemble and disassemble actin allows it to rapidly move or change shape in response to the environment.

The research was reported March 4 in the early online edition of the journal Proceedings of the National Academy of Sciences (PNAS). The work was supported by the National Institutes of Health (NIH).

“For the first time, we have shown that mechanical force can directly regulate how actin is assembled and disassembled,” said Larry McIntire, chair of the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University and corresponding author of the study. “Actin is fundamental to how cells accomplish most of their functions and processes. This research gives us a whole new way of thinking about how a cell can do things like rearrange its cytoskeleton in response to external forces.”

The external forces affecting a cell could arise from such mechanical actions as blood flow, trauma to the body, or the loading of bones and other tissue as organisms move around.

“Forces are applied to cells all the time, and often they are directional, not uniformly applied in a certain direction,” said McIntire. “The cell can rearrange its cytoskeleton to either accommodate the forces that are being applied, or apply its own forces to do something – such as moving to go after food.”

Because these forces regulate the polymerization and depolymerization of actin, they load the actin fibers in a specific direction, affecting the duration of bonds that may influence cellular growth in one direction, he said.

For instance, tensile forces applied to the actin produce catch bonds, in which the bond lifetime increases as the force increases. These catch bonds have been shown to exist in other proteins, but actin is the most important protein known to form the structures. Most bonds at the cellular level are slip bonds which, unlike catch bonds, dissociate more quickly with application of force.

The researchers used a specially-constructed AFM to conduct their experiments. The tip was coated with actin monomers, while a polystyrene surface below the AFM tip was coated with either monomeric or filamentous actin. To study the catch-slip bonds, the tip was driven close to the surface to allow bond formation, then retracted to pull on the bond. The tension was held stationary to measure the bond lifetime at a constant force.

The research team also used molecular dynamics simulations to predict the specific amino acids likely to be important in forming the catch bonds. Experiments using specialized reagents confirmed the molecular mechanism, a lysine-glutamic acid-salt bridge believed to be responsible for forming long-lived bonds between actin sub-units when force is applied to them.

“What we found was that when you apply force, the force induces additional interactions at the atomic scale,” said Cheng Zhu, a Regents’ professor in the Coulter Department of Biomedical Engineering and co-corresponding author of the paper. “When you apply force, you find that residues that had previously not been making contact are now interacting. These are force-induced interactions.”

Proof that force application can play a role in the internal functions of cells demonstrates the growing importance of a relatively new field of research known as mechano-biology, which studies how mechanical activities affect living tissues.

“We know that the cell can sense the mechanical environment around it,” said Zhu, who holds the J. Erskine Love Endowed Chair in Engineering. “One of the cell’s responses to the mechanical environment is to change shape and reorganize the actin cytoskeleton. Previously, it was thought that sensory molecules at the cell surface were required to convert the mechanical cues into biochemical signals before the actin cytoskeleton could be altered. The mechanism we describe can bypass the cellular signaling mechanisms because actin bears the force in the cell.”

The work sets the stage for additional research into other biochemical reactions that may be produced by the application of force.

“It’s becoming more and more clear that the ability of the cell to vary its mechanical environment, in addition to responding to what’s going on outside it, is crucial to a lot of what goes on with the biochemistry in the cell functions,” McIntire added. “If you can change the structure of the amino acids by pulling on them, and that force is applied to an enzymatic site, you can increase or decrease the enzymatic activity by changing the local structure of the amino acids.”

The research was inspired by a 2005 paper from the Shu Chien lab at the University of California at San Diego, and was carried out by Georgia Tech graduate student Cho-yin Lee (now at the National Taiwan University Hospital) and research scientist Jizhong Lou (now at the Chinese Academy of Sciences), with intellectual input from Suzanne B. Eskin from Georgia Tech and Shoichiro Ono from Emory University.  Kuo-kuang Wen and Melissa McKane from the laboratory of Peter A. Rubenstein at the University of Iowa provided actin mutants used in the research.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More Than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Predictive Model for Breast Cancer Progression
Biomedical engineers have demonstrated a proof-of-principle technique that could give women and their oncologists more personalized information to help them choose options for treating breast cancer.
Tuesday, October 06, 2015
Microneedle Patch For Measles Vaccination Could Be A Global Game Changer
A new microneedle patch being developed by the Georgia Institute of Technology and the Centers for Disease Control and Prevention (CDC) could make it easier to vaccinate people against measles and other vaccine-preventable diseases.
Wednesday, April 29, 2015
Studies Reveal Diverse Molecular Mechanisms Underlying Evolution
Researchers have sequenced the genomes and transcriptomes of five species of African cichlid fishes and uncovered a variety of features that enabled the fishes to thrive in new habitats and ecological niches within the Great Lakes of East Africa.
Monday, September 08, 2014
New Evidence that Cancer Cells Change While Moving throughout Body
For the majority of cancer patients it is the spread or “metastasis” of cancer cells from the primary tumor to secondary locations throughout the body that is the problem.
Wednesday, September 04, 2013
Startup Launched from Georgia Tech-Emory University Research Receives $7.9 Million
Clearside Biomedical, Inc. has received $7.9 million in funding to continue drug and technology development for treatment of ocular diseases.
Tuesday, April 02, 2013
Genetic Packing: Successful Stem Cell Differentiation Requires DNA Compaction, Study Finds
New research findings show that embryonic stem cells unable to fully compact the DNA inside them cannot complete their primary task: differentiation into specific cell types that give rise to the various types of tissues and structures in the body.
Wednesday, May 16, 2012
Scientific News
High Throughput Mass Spectrometry-Based Screening Assay Trends
Dr John Comley provides an insight into HT MS-based screening with a focus on future user requirements and preferences.
Promising Drug Combination for Advanced Prostate Cancer
A new drug combination may be effective in treating men with metastatic prostate cancer. Preliminary results of this new approach are encouraging and have led to an ongoing international study being conducted in 196 hospitals worldwide.
A Cellular Symphony Responsible for Autoimmune Disease
Broad Institute researchers have used a novel approach to increase our understanding of the immune system as a whole.
When it Comes to Breast Cancer, Common Pigeon is No Bird Brain
If pigeons went to medical school and specialized in pathology or radiology, they’d be pretty good at distinguishing digitized microscope slides and mammograms of normal vs. cancerous breast tissue, a new study has found.
Editing of LIMS Data Made Faster and More Efficient in Matrix Gemini
The latest version of the Matrix Gemini LIMS (Laboratory Information Management System) from Autoscribe Informatics now provides faster and more efficient editing of LIMS data by eliminating the need for a second editing screen.
University of Edinburgh, Selcia Achieve Key Milestones in Drug Development Program
Scientists from the University of Edinburgh, working with Selcia, have successfully passed the 20-month milestone targets of a 30-month Wellcome Trust SDDi £2.5 million project to design novel treatments for sleeping sickness.
Red Clover Genome to Help Restore Sustainable Farming
The Genome Analysis Centre (TGAC) in collaboration with IBERS, has sequenced and assembled the DNA of red clover to help breeders improve the beneficial traits of this important forage crop.
How a Genetic Locus Protects Adult Blood-Forming Stem Cells
Mammalian imprinted Gtl2 protects adult hematopoietic stem cells by restricting metabolic activity in the cells' mitochondria.
Genetic Basis of Fatal Flu Side Effect Discovered
A group of people with fatal H1N1 flu died after their viral infections triggered a deadly hyperinflammatory disorder in susceptible individuals with gene mutations linked to the overactive immune response, according to a recent study.
New Tech Vastly Improves CRISPR/Cas9 Accuracy
A new CRISPR/Cas9 technology developed by scientists at UMass Medical School is precise enough to surgically edit DNA at nearly any genomic location, while avoiding potentially harmful off-target changes typically seen in standard CRISPR gene editing techniques.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos