Navigation Links
UCLA study shows cell-penetrating peptides for drug delivery act like a Swiss Army Knife

Cell-penetrating peptides, such as the HIV TAT peptide, are able to enter cells using a number of mechanisms, from direct entry to endocytosis, a process by which cells internalize molecules by engulfing them.

Further, these cell-penetrating peptides, or CPPs, can facilitate the cellular transfer of various molecular cargoes, from small chemical molecules to nano-sized particles and large fragments of DNA. Because of this ability, CPPs hold great potential as in vitro and in vivo delivery vehicles for use in research and for the targeted delivery of therapeutics to individual cells.

But exactly how cell-penetrating peptides and particularly the HIV TAT peptide accomplish these tasks has so far been a mystery.

"The HIV TAT peptide is special. People discovered that one can attach almost anything to this peptide and it could drag it across the cell," said Gerard Wong, a professor of bioengineering and of chemistry and biochemistry at the UCLA Henry Samueli School of Engineering and Applied Science and the California NanoSystems Institute at UCLA. "So there are obvious beneficial drug-delivery and biotechnology applications."

In a new study published in Proceedings of the National Academy of Sciences, UCLA Engineering researchers, including Wong and bioengineering professors Timothy Deming and Daniel Kamei, identify how HIV TAT peptides can have multiple interactions with the cell membrane, the actin cytoskeleton and specific cell-surface receptors to produce multiple pathways of translocation under different conditions.

Moreover, because the researchers now understand how cell-penetrating peptides work, they say it is possible to formulate a general recipe for reprograming normal peptides into CPPs.

"Prior to this, people didn't really know how it all worked, but we found that the HIV TAT peptide is really kind of like a Swiss Army Knife molecule, in that it can interact very strongly with membranes, as well as with the cytoskeletons of cells," said Wong, the study's lead author. "The second part wasn't well appreciated by the field."

In addition to the membrane activity, researchers discovered that the HIV TAT peptide also creates its own binding site out of the membrane. This means the peptide can actually go through the membrane and induce the cytoskeleton directly to have an endocytotic event.

"We found that there are two channels of activity," Wong said. "Because of the peculiar sequence of HIV TAT, it's very good at being able to interact with membranes. Further, with the high-density packing of charged amino acids in the peptide, it can also interact very strongly with the cell's cytoskeleton, as well as its receptors."

In addition, the researchers noticed that small cargoes can be transferred directly, while cargoes larger than a few nanometers needed to be anchored to the membrane by the TAT peptide.

Deming, who specializes in synthetic methods, prepared the polypeptide samples for use in the experiments. Kamei, an expert in cellular trafficking, performed cell-based endocytosis experiments using inhibitor drugs and confocal microscopy to identify dominant mechanisms of endocytosis.

"This research is exciting because cell-penetrating peptides have been used in the area of drug delivery for some time," Kamei said. "Gaining any additional understanding of these delivery agents will help in future drug-carrier designs."

It is the group's hope that the new understanding gained from their study will be used to engineer new molecules that are more effective in delivering therapeutic agents.

"This collaboration was important because it combined expertise in the areas of synthesis, characterization and cellular trafficking to address a very relevant problem," Kamei said. "I definitely see more opportunity for combining these areas to tackle other problems in the growing field of biomaterials."


Contact: Wileen Wong Kromhout
University of California - Los Angeles

Related biology news :

1. Long-term study shows effect of climate change on animal diversity
2. £2 million study to reveal workings of dementia genes
3. New study looks to define evangelicals and how they affect polling
4. CU-Boulder study suggests air quality regulations miss key pollutants
5. Researchers study acoustic communication in deep-sea fish
6. Study reveals homeowner perceptions in fire-prone areas
7. Researchers study how pistachios may improve heart health
8. Study: urban black bears live fast, die young
9. New study indicates link between weight gains during pregnancy and dieting history
10. Study reveals specific gene in adolescent men with delinquent peers
11. Sweat it out: UH study examines ability of sweat patches to monitor bone loss
Post Your Comments:
(Date:10/12/2015)... , Oct. 12, 2015 ... end-to-end authentication infrastructure company, will introduce its ... captures four prints simultaneously, providing an unprecedented ... well as discuss the new biometric standard ... highlight how enterprises from financial services to ...
(Date:10/8/2015)... , 8. Oktober 2015 Die ... tätiges Unternehmen des Bereiches Tracking, hat heute ... der Gefängnisbehörde Virginias (Department of Corrections – ... Überwachungsdienste für alle Strafen geliefert werden, die ... , Präsident für den Amerikanischen Kontinent der ...
(Date:10/6/2015)... , Oct. 6, 2015  Maverix Biomics, ... announced enhancements to its software portfolio with the ... kit for differential expression in eukaryotes. The software ... is a cloud-based genomic analysis solution that leverages ... discovery from next-generation sequencing efforts. Garry ...
Breaking Biology News(10 mins):
(Date:10/13/2015)... , October 13, 2015 ... in the development of innovative peptide and gene-based immunotherapeutics ... disease, will be a featured presenting company at the ... the Wyndham Grand Hotel in Jupiter, Florida ... TapImmune, Inc. (TPIV), a clinical-stage immunotherapy company specializing ...
(Date:10/13/2015)... ... October 13, 2015 , ... SonaCare ... announced today that it received de novo clearance from the U.S. Food and ... the ablation of prostate tissue. Sonablate® is the first High Intensity Therapeutic Ultrasound ...
(Date:10/12/2015)... ... October 12, 2015 , ... Spirax Sarco, the leader ... of the CSM-C 600 compact clean steam generator . This unit is ... the requirements of HTM2031, HTM2010, and EN285 standards. The CMS-C 600 generator can ...
(Date:10/12/2015)... , 12 de octubre de 2015 El ... llegó a un récord en el congreso con su ... de la International Plasma Awareness Week (IPAW), que se ... está patrocinada por la Plasma Protein Therapeutics Association ... , Aumentar la concienciación mundial acerca ...
Breaking Biology Technology: