Futuristic? Only in part. A research team from Northwestern University’s Institute for BioNanotechnology in Medicine has created such sacs and demonstrated that human stem cells will grow in them. The researchers also report that the sacs can survive for weeks in culture and that their membranes are permeable to proteins. Proteins, even large ones, can travel freely across the membrane.
This new and unexpected mode of self-assembly, to be published March 28 in the journal
Science, also can produce thin films whose size and shape can be tailored. The method holds promise for use in cell therapy and other biological applications as well as in the design of electronic devices by self-assembly, such as solar cells, and the design of new materials.
“We started with two molecules of interest, dissolved in water, and brought the two solutions together,” said Samuel I. Stupp, Board of Trustees Professor of Materials Science and Engineering, Chemistry and Medicine, who led the research.
“We expected them to mix, but, much to our surprise, they formed a solid membrane instantly on contact. This was an exciting discovery, and we then proceeded to investigate why it happened. Understanding the surprising molecular mechanism was even more exciting.”
One of the molecules is a peptide amphiphile (PA), small synthetic molecules that Stupp first developed seven years ago, which have been essential in his work on regenerative medicine. The other molecule is the biopolymer hyaluronic acid (HA), which is readily found in the human body, in places like joints and cartilage. Stupp recently had started a new research project on the regenerative medicine of cartilage, which drew him to hyaluronic acid.
“This is a clear example of informed discovery,” said Stupp, director of the Institute for BioNanotechnology in Medicine. “We knew there was something interesting about the interaction between peptide amphiphiles and biopolymers from our previous work on nanostructures that can cause blood vessels to grow. And we were particularly interested in hyaluronic acid because of its role in cartilage, a tissue that adults cannot regenerate and, when damaged in joints, causes grief to humans.”
Using just these two molecules, Stupp and his team can make many different structures, the two most important being sacs, which have a solid membrane on the outside and liquid inside, and flat membranes of any shape. The researchers can make the structures large or small, pick up the material with tweezers, stretch it and even easily repair the sacs through self-assembly should the material tear or have some other defect. The sacs also are robust enough to be sutured by surgeons to biological tissues.
The large (hyaluronic acid) and small (peptide amphiphile) molecules come together through supramolecular interactions, not by chemical reaction, in which covalent bonds are formed.
In the case of the flat membrane, the researchers put the peptide amphiphile solution at the bottom of a shallow mold and added on top the hyaluronic acid solution. The two interacted on contact, creating a solid. By varying the mold, the researchers produced a variety of shapes, including stars, triangles and hexagons, each having two chemically different surfaces. When dry, the materials are stiff and strong, like plastic.
In creating a sac, the researchers took advantage of the fact that hyaluronic acid (HA) molecules are larger and heavier than the smaller peptide amphiphile (PA) molecules. In a deep vial, they poured the PA solution and into that poured the HA solution. As the heavier molecules sank, the lighter molecules engulfed them, creating a closed sac with the HA solution trapped inside the membrane.
Having formed the sacs, Stupp and his team next studied human stem cells engulfed by the self-assembly process inside sacs that they placed in culture. The researchers found that the cells remained viable for up to four weeks, that a large protein -- a growth factor important in the signaling of stem cells -- could cross the membrane, and that the stem cells were able to differentiate.
“We expect that genes, siRNAs and antibodies will cross the membranes as well, making this mini cell biology lab a powerful device for research or therapies,” said Stupp. “For the development of cancer therapies, we will be able to confine cells within the sacs and study their reaction to different types of therapies as well as to signaling by different cells in neighboring sacs.”
In a clever demonstration of self-repair, if the sac’s membrane had a hole (from a needle injection, for example), the researchers simply placed a drop of the PA solution on the tear, which interacted with the HA inside, resulting in self-assembly and a sealed hole.
“The membrane is a fascinating and unusual structure with a high degree of hierarchical order,” said Stupp. “The membrane grows through a dynamic self-assembly process which generates hybrid nanofibers made up of both molecules and oriented perpendicular to the plane of the membrane. This architecture is very difficult to get spontaneously in materials. Using the right chemistry, the thick membrane structure could be designed to get conduits of charge in solar cells or nanoscale columns of catalytic nanostructures that would extend over arbitrary macroscopic dimensions.”
While the underlying, highly ordered structure of the sacs and membranes has dimensions on the nanoscale, the sacs and membranes themselves can be of any dimension and are visible to the naked eye.
Video: Self-assembling sacs form instantly when two aqueous solutions, one containing small molecules (first drop) and another containing high molecular weight polymers (green drop), are brought together.
Source: Northwestern University
Related stories:
Tiny sacs released by brain tumor cells carry information that may guide treatment
Microvesicles – tiny membrane-covered sacs – released from glioblastoma cells contain molecules that may provide data that can guide treatment of the deadly brain tumor. In their report in the December 2008
Nature Cell Biology, which is receiving early online release, Massachusetts General Hospital (MGH) researchers describe finding tumor-associated RNA and proteins in membrane microvesicles called exosomes in blood samples from glioblastoma patients. Detailed analysis of exosome contents identified factors that could facilitate a tumor's growth through delivery of genetic information or proteins, or signify its vulnerability to particular medications.
In scientific first, researchers correct decline in organ function associated with old age
As people age, their cells become less efficient at getting rid of damaged protein — resulting in a buildup of toxic material that is especially pronounced in Alzheimer's, Parkinson's disease, and other neurodegenerative disorders.
Einstein researchers discover important clue to the cause of Parkinson's disease
A glitch in the mechanism by which cells recycle damaged components may trigger Parkinson’s disease, according to a study by scientists at the Albert Einstein College of Medicine of Yeshiva University. The research, which appears in the January 2 advance online issue of The Journal of Clinical Investigation, could lead to new strategies for treating Parkinson’s and other neurodegenerative diseases.
How sneaky HIV escapes cells
Like hobos on a train, HIV, the virus that causes AIDS, uses a pre-existing transport system to leave one infected cell and infect new ones, Hopkins scientists have discovered. Their findings, published in the June issue of
Plos Biology, counter the prevailing belief that HIV and other retroviruses can only leave and enter cells by virus-specific mechanisms.
Crossing scientific boundaries to understand the rejection of drugs
A physicist from The University of Nottingham and a mathematical modeller from The University of Southampton are joining forces in the hope of answering a biological mystery — how do our bodies reject some of the drugs that are sent to cure us?
Persistent pollutant may promote obesity
Tributyltin, a ubiquitous pollutant that has a potent effect on gene activity, could be promoting obesity, according to an article in the December issue of
BioScience. The chemical is used in antifouling paints for boats, as a wood and textile preservative, and as a pesticide on high-value food crops, among many other applications.
Scientists discover a new way in which epigenetic information is inherited
Hereditary information flows from parents to offspring not just through DNA but also through the millions of proteins and other molecules that cling to it. These modifications of DNA, known as "epigenetic marks," act both as a switch and a dial – they can determine which genes should be turned on or off, and how much message an "on" gene should produce.
Scientists show how a protein that determines cell polarity prevents breast cancer
In breast tissue, cells lining the breast's ducts have a certain shape that is required to maintain both organ structure and function. All breast cancers display a loss of this characteristic organization, but very little is known about the molecules and pathways that regulate tissue structure and the role they play during cancer.
