Self-assembling bubbles and membranes for cell culture and much more

Working under the guidance of Professor Samuel I. Stupp, scientists at the Institute of BioNanotechnology in Medicine, part of Northwestern University (Chicago, USA), have developed a method of self-assembly of bubbles suitable for encapsulation and cell growth in culture. Stem cells placed inside the vesicles function normally for several weeks. This is due to the fact that the bubble membrane is permeable even to the largest protein molecules.

The researchers started working with two compounds of interest to them, which they dissolved in water and tried to mix the resulting solutions. Quite unexpectedly, at the moment of contact of liquids, a dense membrane was instantly formed, and scientists devoted further work to the study of the mechanisms of formation of which.

One of the compounds used in the work was the amphiphile peptide (peptide amphiphile, PA) synthesized by Stapp for the first time seven years ago, the small molecules of which played an important role in his work on regenerative medicine. The second compound is hyaluronic acid, a biopolymer found in the body as part of joints and cartilage.

Using these two compounds allowed scientists to create many different structures, the most important of which are liquid-filled dense membrane bubbles and flat membranes. The structures being created can be of almost any size and shape, manipulations can be performed on them with tweezers, as well as possible damage can be repaired by activating the self-assembly mechanism. Moreover, the material is strong enough and it can be sewn to biological tissues using suture material.

Large (hyaluronic acid) and small (amphiphilic peptide) molecules combine due to supramolecular interactions, and not covalent bonds, as in chemical reactions.

To create flat membranes, an amphiphilic peptide solution is placed on the bottom of a shallow container, on top of which a solution of hyaluronic acid is layered. As a result, a solid membrane is formed in the contact zone of liquids. With the help of various containers, the researchers obtained membranes of various shapes, including in the form of stars, triangles and hexagons. The opposite surfaces of such membranes have different chemical properties. When dried, the membranes acquire the density and strength of plastic.

For the formation of bubbles, the key point is the fact that hyaluronic acid molecules are larger and heavier than amphiphilic peptide molecules. The synthesis process in this case consists in pouring a solution of hyaluronic acid into a deep test tube filled with an amphiphilic peptide solution. As its heavy molecules sink, lighter peptide molecules cover the descending solution, resulting in the formation of a membrane bubble containing a solution of hyaluronic acid. (The process of forming a tiny bubble, not in a test tube, but in a drop of solution, can be seen in the video – short, but impressive). Damage to such bubbles is restored by placing a drop of an amphiphilic peptide solution at the rupture site, which is instantly tightened.

The authors also studied the viability of stem cells trapped inside membrane vesicles during self-assembly. When cultured in an appropriate nutrient medium (it gives the bubble a pinkish color in the figure), the cells contained in the bubbles remained viable for four weeks. In addition, the membrane is permeable even to large protein molecules of growth factors, which, penetrating into the vesicles, stimulate cell differentiation.

According to Stapp, genes, miRNAs and antibodies must also penetrate the membrane, which indicates the great potential of using the invention for research and medical purposes. For example, tumor cells can be placed inside such bubbles and their reactions to various treatments, as well as to molecular signals released by cells contained in neighboring bubbles, can be studied.

The membrane has a unique hierarchical structure. It is formed as a result of a dynamic self-assembly process and consists of hybrid fibers arranged perpendicular to the membrane plane, which include two types of molecules. Such a structure is very difficult to obtain with spontaneous self-assembly of materials. The authors believe that the selection of optimal compounds will make it possible to create, for example, a thick membrane structure suitable for the production of solar batteries, or nanocolons for catalytic nanodevices.

While the structure of bubbles and membranes is strictly ordered at the nanoscale, the bubbles and membranes themselves are not only visible to the naked eye, but can be almost any size.

Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of Northwestern University

04.04.2008