Navigation Links
Motor proteins may be vehicles for drug delivery
Date:3/20/2009

Specialized motor proteins that transport cargo within cells could be turned into nanoscale machines for drug delivery, according to bioengineers. Chemical alteration of the proteins' function could also help inhibit the growth of cancerous tumors.

Each cell in the body contains motor proteins that ferry cargo such as chromosomes, mitochondria or bundles of proteins, either from the center of the cell to its outskirts or from the periphery toward the nucleus. Most motor proteins contain two motor domains, or heads, that are attached to a shared cargo-binding domain, or tail.

"Think of it as a freight train at the molecular level," said William Hancock, associate professor of bioengineering, Penn State. "And it runs on cylindrical tracks -- or microtubules -- made of many protein subunits meshed together into a long polymer that is one ten thousandth the diameter of hair."

Hancock and his colleagues are studying a particular motor protein known as kinesin-2. They are trying to understand the molecular mechanics of how these nanometer-scale proteins move within the cell.

"Kinesin motor proteins move by changing their shape," explains Hancock. "The two motor domains alternately bind to the microtubule, generate force and then detach, and the resulting displacement drags the cargo forward."

To power this hand-over-hand motion, the proteins convert the chemical energy of ATP molecules -- a common energy source in cells -- into mechanical work. But there is a problem if the proteins fall off their tracks.

"When a motor binds to the microtubule, it 'walks' about 100 steps -- each step being eight nanometers -- before detaching," said Hancock, whose findings appeared in a recent issue of Current Biology. "And the proteins are so small that if both motor domains let go, the proteins and their cargo would diffuse away within a few milliseconds. This profound effect of diffusion is one of the places where the nanoscale world fundamentally differs from the macro-scale world we normally live in."

The key to successfully hauling the cargo from one point to another lies in perfect coordination between the two motor domains. At any given time, one of the motor domains always needs to be bound to the track.

"Each motor domain is by itself an enzyme that continually alters the mechanics and the biochemistry of the other," explained Hancock, whose work is funded by the National Institutes of Health. "And we are trying to understand the mechanical coordination between the two domains. You can think of it like walking on two feet, but there's no brain to control when a step is taken, only a mechanical connection between the two feet."

The researchers have found that the tether that links the motor domains to the rest of the molecule is longer in kinesin-2 motors than in other kinesin proteins, which prevents efficient mechanical coordination between the two motor domains.

"If you think of this linker domain as a taut bungee cord, any force at one end will be communicated very efficiently to the other end. So the two motors can communicate very efficiently and the timing of their steps is tightly coordinated," Hancock said. "But if the cord is very loose, the forces from one motor domain are poorly communicated to the other and the precise timing of their steps is disrupted. This is a big effect and it reduces the performance of kinesin-2."

To confirm their findings, the researchers artificially lengthened the tethers on kinesin-1 motor proteins. These motors ferry chemicals over much greater distances -- such as in neurons that can be a meter long -- and the coordination between their two motor domains is very efficient.

The researchers found that when the tethers on kinesin-1 motors were lengthened, the communication between the two heads was diminished.

Hancock believes that the insight into the relationship between the length of the tether and the communication between the motor domains could offer new targets for drugs that inhibit kinesins.

"There are a lot of kinesins involved in cell division, and cancer is uncontrolled cell division," said Hancock. "Our hope is that this knowledge will help in the design of new drugs that block the motors during cell division and thereby slow the growth of tumors."

The researchers also believe that the kinesin transport system could in the future be engineered onto microchips.

"Our idea is that you can hook up cargo -- drugs, antibodies, sequences of DNA or RNA -- and the motors would carry them through microchannels on a lab-on-a-chip type of device," added Hancock. "We have already had success with incorporating these proteins into microengineered channels and achieving transport in these systems."


'/>"/>

Contact: Amitabh Avasthi
aem1@psu.edu
814-865-9481
Penn State
Source:Eurekalert

Related medicine news :

1. VIDEO from Medialink and General Motors: On and Off the Track
2. CDC Study Links Thimerosal in Vaccines to Motor/Phonic Tics and Deficits in Attention, Behavior Control, Verbal IQ
3. Hospital-led Coalition Cautions Motorists on New Risks October 1, Lauds Legislative Leaders for Scheduling No-fault Hearings Next Week
4. Paramed Announces Release of Motorized Stair-Climbing Chair
5. General Mills #43, M&Ms #38 Driving Passionately Pink for the Cure at Lowes Motor Speedway NASCAR Race
6. General Motors, Virginia Tech scientists collaborate to advance neuroinformatics
7. New Book Links Motorcycle Radiation to Cancer Risk
8. Motorcycle Radiation May Be Linked to Cancer Risk
9. Songbirds offer clues to highly practiced motor skills in humans
10. Ford Motor Company Fund Continues Longtime Support to Cancer Care
11. CVS Samaritan Van Program Celebrates 30 Years of Helping Motorists on the Nations Highways
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/11/2016)... St. Petersburg, FL (PRWEB) , ... February 11, ... ... care providers and advocates will discuss how to improve care by making data ... and pediatric heart disease. The Summit on Transparency and Public Reporting of Pediatric ...
(Date:2/11/2016)... ... February 11, 2016 , ... veEDIS Clinical ... technology, with highly adaptable algorithms, has been updated to help Emergency Department physicians ... symptoms consistent with Zikas and a travel history to affected regions, or potential ...
(Date:2/11/2016)... ... February 11, 2016 , ... Life is known for throwing curves. It’s ... older, who gather once a year to play softball to raise money through ... the more than 50 players who competed in this year’s softball tournament share a ...
(Date:2/11/2016)... FRANCISCO (PRWEB) , ... February 11, 2016 , ... ... Houston-based multi-specialty practice Village Family Practice , will be presenting at the ... 2016, in Las Vegas, Nev. , During his session, “ Coding for ...
(Date:2/11/2016)... ... 11, 2016 , ... Pixel Film Studios brings the spirit of the holiday ... Christmas edition of the ProDrop series. Pick and choose from 30 unique designs inspired ... of Christmas using ProDrop's wintry generators. ProDrop Christmas is a Final Cut Pro X ...
Breaking Medicine News(10 mins):
(Date:2/11/2016)... , Feb. 11, 2016  Proliant Biologicals is proud ... Serum Albumin (BSA) manufacturing facility.  The facility is located ... , in Feilding. Boone ... to functionally duplicate the systems in the U.S. facility, ... used for U.S. installations.  --> ...
(Date:2/11/2016)... Breast Cancer Therapeutics in Asia-Pacific Markets to 2021 ... breast cancer market will experience considerable expansion from $1.9 billion ... Annual Growth Rate (CAGR) of 8.5%. --> Breast ... that the Asia-Pacific (APAC) breast cancer ... to $3.4 billion by 2021, at a Compound Annual Growth ...
(Date:2/11/2016)... , Feb. 11, 2016  AbbVie, a ... AbbVie Rheumatology Scholarship, designed to provide financial support ... as they pursue higher education goals. Fifteen scholars ... the 2016-2017 school year. The AbbVie Rheumatology Scholarship ... Haas , vice president, corporate social responsibility, brand ...
Breaking Medicine Technology: