Plastic shows promise for use in human body

Engineers at The University of Texas at Austin have found a way to modify a plastic to anchor molecules that promote nerve regeneration, blood vessel growth or other biological processes.

In the study led by Dr. Christine Schmidt, the researchers identified a piece of protein from among a billion candidates that could perform the unusual feat of attaching to polypyrrole, a synthetic polymer (plastic) that conducts electricity and has shown promise in biomedical applications. When the protein piece, or peptide, was linked to a smaller protein piece that human cells like to attach to, polypyrrole gained the ability to attach to cells grown in flasks in the laboratory.

“It will be very useful from a biomedical standpoint to be able to link factors to polypyrrole in the future that stimulate nerve growth or serve other functions,” said Schmidt, an associate professor of biomedical engineering at the university.

Schmidt is the principal author for the study conducted with colleague Dr. Angela Belcher at Massachusetts Institute of Technology. It was published online May 15 by the journal Nature Materials.

Polypyrrole is of interest for tissue engineering and other purposes because it is a non-toxic plastic that conducts electricity. As a result, it could be used to extend previous experiments in Schmidt’s laboratory. The experiments involve wrapping a tiny strip of plastic around damaged, cable-like extensions of nerve cells called neurites to help them regenerate.

“We can apply an electric field to this synthetic material and enhance neurite repair,” said Schmidt. The newly gained ability to attach proteins to polypyrrole, she said, will mean that growth-enhancing factors could also be linked to this plastic wrapping, further stimulating neurite regeneration.

Working with Schmidt and Belcher, the paper’s lead authors, graduate students Archit Sanghvi and Kiley Miller identified the peptide that attaches to polypyrrole from among the billion alternatives initially analyzed. These unique peptides were displayed on the outer surface of a harmless type of virus called a bacteriophage that was purchased commercially.

To hunt for the plastic-preferring peptide, Sanghvi and Miller added a solution containing bacteriophages that displayed different peptides to a container with polypyrrole stuck on its inner surface. The bacteriophages that didn’t wash away when exposed to conditions that hinder attachment were retested on a new polypyrrole-coated container, a process that was repeated four more times.

The sticky peptide selected, known as T59, is a string of 12 amino acids. To make certain that something else on the outer surface of the bacteriophage virus wasn’t responsible for its perceived stickiness, the researchers demonstrated that T59 by itself could attach to immobilized polypyrrole, using synthetic copies of it made at the university’s Institute for Cellular and Molecular Biology. In addition, they determined that a certain amino acid, aspartic acid, had to be a part of T59 for it to attach well to the plastic.

Aspartic acid carries a negative charge, which in T59 appeared to be drawn to the positively charged surface of the polypyrrole the way magnets of opposite charges cling together. Yet other peptides containing aspartic acid didn’t attach to polypyrrole, leading the researchers to speculate that something contributed by the other amino acids in T59 influenced its 3-dimensional shape in a way that augmented its plastic preference.

“This aspartic acid is just one piece of the puzzle,” Sanghvi said. “There are still more pieces to put together.”

The researchers also evaluated how well T59 clings to polypyrrole. They attached copies of the peptide to the tip of an atomic force microscope at the university’s Center for Nano- and Molecular Science and Technology. The tip of this specialized microscope is normally passed across the surface of a material to “map” its peaks and valleys. In this case, the surface was a layer of polypyrrole, and the resistance of the peptide-coated tip to being passed across the surface revealed how well T59 clung to the plastic.

“They had a moderately strong interaction, which is useful to know,” Schmidt said, referring to the need for a stable attachment between polypyrrole and biological molecules that T59 would be used to link to.

Schmidt’s laboratory intends to study T59 as a linker to other molecules in the future, possibly including vascular endothelial growth factor, which stimulates the growth of new blood vessels. In addition, they will use the bacteriophage analysis approach, called high-throughput combinatorial screening, to look for peptide linkers for other plastics such as polyglycolic acid under study for tissue-repair or tissue-engineering purposes.

“This is a powerful technique that can be used for biomaterials modification,” Schmidt said, “and it hasn’t really been explored very much until now.”

From UT Austin

    據(jù)英國《自然》雜志2005年5月15日報道,，美國德克薩斯大學的科學家們將特定塑膠粘附于人體分子上，可應用于促進神經(jīng)再生、血管生長等生物學領域,。

    該項目的研究人員對十億個蛋白質塊進行挑選，確定其中一個能有效粘附在一種名叫聚咯（polypyrrole）的塑膠上,。聚咯是一種聚合體（塑膠）,，具有很強的導電性和生物活性。一旦蛋白質塊或縮氨酸與更小的蛋白質塊相連接,，聚咯就能夠粘附于其中的細胞上,。

    項目負責人施密特指出，從生物醫(yī)學的角度來看,，這項研究非常有用,。聚咯作為一種能導電的無毒塑膠，在組織工程等方面具有很大的價值,。施密特用一小條聚咯將受損的神經(jīng)突包裹起來,，以幫助其再生。她說：“我們可以在這種合成材料上加上電場,，以此來提高神經(jīng)突的再生能力,。”

    同時，研究人員還從數(shù)十億個蛋白質塊中確定了一種獨特的縮氨酸,。這種縮氨酸通常利用一種被稱為抗菌素的無害病毒外表面來顯示,。為了尋求具有親-塑膠性的縮氨酸，他們將一種含有抗菌素的溶液加入容器中,，并將聚咯粘附在容器的內(nèi)表面上,。然后把沒有沖掉的抗菌素倒入另一個內(nèi)表面覆有聚咯的容器內(nèi)，如此重復4次,。

    德克薩斯大學細胞和分子生物學研究所的科學家利用人造模式證明了,，這種被稱為T59的粘性縮氨酸具有極強的粘性。此外,，他們還確定T59種有某種特定的氨酸基——天冬氨酸,，有助于增強T59在塑膠上的粘附性能。

    天冬氨酸帶有一個負電子，因此能夠與聚咯表面的正電子相互吸引,。但是其它包含有天冬氨酸的縮氨酸無法粘附于聚咯上,，研究人員推測可能是由于T59種其它氨基酸影響了其3-D形狀，增強了其親-塑膠的性能,。

    研究人員還對T59在塑膠上的粘性進行了評估,。他們將縮氨酸粘附于原子顯微鏡的探針上，然后將探針通過一層聚咯表面,，探針產(chǎn)生的阻力就顯示出T59與塑膠的粘性,。

    施密特實驗室準備將T59作為未來分子間連接器進行研究，此外,，他們還將利用抗菌素分析方法來尋求其它可粘附有縮氨酸的塑膠,。