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Gene Therapy: Polymer Translocation Pulled through a Narrow Pore

Date:
March 12, 2008
Source:
Biophysical Society
Summary:
When polymeric molecules squeeze through a nanometer-sized pore in membranes, in a process known as translocation, they leave a distinct signature at the pore. Present-day techniques can exploit translocation to recognize individual polymeric molecules by analyzing these signatures. Interestingly, one encounters translocation more frequently as a serious bottleneck: the prospect of polymeric molecules passing through nanometer-sized pores in inter/intra-cellular membranes hinders efficient delivery of drug molecules to their activation sites, and of healthy gene fragments to their target sites in gene therapy.
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When polymeric molecules squeeze through a nanometer-sized pore in membranes, in a process known as translocation, they leave a distinct signature at the pore. Present-day techniques can exploit translocation to recognize individual polymeric molecules by analyzing these signatures. Interestingly, one encounters translocation more frequently as a serious bottleneck: the prospect of polymeric molecules passing through nanometer-sized pores in inter/intra-cellular membranes hinders efficient delivery of drug molecules to their activation sites, and of healthy gene fragments to their target sites in gene therapy.

The physics of translocation is complex since our intuition, based on the macroscopic world, fails: concepts, such as "translocation is slow because the pore resists the passage of the molecule through friction", cannot be trusted at the nanoscale. Instead, other concepts like fluctuations in translocation dynamics at a molecular level are much more important.

Recently, we have made a significant breakthrough in understanding the physics of translocation. Starting from the microscopic dynamics of the polymeric molecule, we showed that its translocation behavior is strongly dominated by "memory effects" in the molecule. Each translocative step forward for the molecule through the pore generates a restoring tension that makes a following backward step through the pore very likely: as if the molecule remembers that it took a step forward, and it wants to return to the previous step.

Consequently, every part of the molecule passes back and forth through the pore many, many times. Two most striking consequences of these wild fluctuations are that under a constant pulling force, the speed of translocation is not uniform; and that a molecule twice as long does not take twice, but four times longer to translocate.

Having unraveled the memory effects of the molecule, we are in a pivotal position to devise new methods to suppress or enhance these memory effects --- and consequently, the back-and-forth fluctuation movements of the molecule through the pore --- by putting in control mechanisms to suit situation-specific requirements. For example, to facilitate faster delivery of drug molecules or healthy gene fragments one needs to suppress the memory effects, while to advance single-molecule characterization techniques using translocation, enhancement of the memory effects is required, so that a given part of the molecule revisits the pore more frequently.

The article titled "Passage Times for Polymer Translocation Pulled through a Narrow Pore" appears in Volume 94, Issue 5, of the Biophysical Journal, which is available online.


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Biophysical Society. "Gene Therapy: Polymer Translocation Pulled through a Narrow Pore." ScienceDaily. ScienceDaily, 12 March 2008. <www.sciencedaily.com/releases/2008/03/080310164903.htm>.
Biophysical Society. (2008, March 12). Gene Therapy: Polymer Translocation Pulled through a Narrow Pore. ScienceDaily. Retrieved July 22, 2024 from www.sciencedaily.com/releases/2008/03/080310164903.htm
Biophysical Society. "Gene Therapy: Polymer Translocation Pulled through a Narrow Pore." ScienceDaily. www.sciencedaily.com/releases/2008/03/080310164903.htm (accessed July 22, 2024).

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