Three-dimensional heart muscle on a two-dimensional chip
Researchers at Johns Hopkins University (Baltimore, Maryland), working under the leadership of Andre Levchenko, in collaboration with colleagues from Seoul National University (Korea), have created a chip that, thanks to the unique nanorelief of the surface, allows you to grow cardiac muscle tissue that practically does not differ from natural. It is noteworthy that for the formation of muscle tissue, cardiomyocytes did not need any chemical factors, but followed exclusively their "nano-sense", which allowed them to read the information necessary for growth and functioning from the nanorelief of the chip surface.
The development and functioning of all tissues, including the heart muscle, in the body directs and supports the extracellular (extracellular) matrix – a highly structured framework consisting of fibers. Therefore, muscle tissue grown on a flat surface will never have all the characteristics of the tissue of a living organism.
To solve this problem, scientists have developed a chip whose consistency and surface structure correspond to the parameters of the extracellular matrix as much as possible. The chip consists of a glass base on which a layer of hydrogel is applied, made of biocompatible polyethylene glycol and having a complex two-dimensional structure represented by long grooves and scars. Researchers have created various variants of chips, with the width of the grooves from 50 to 800 nm, the width of the scars – from 150 to 800 nm and the height of the scars – from 200 to 500 nm. This made it possible to regulate the structure of the grown muscle tissue.
Cardiomyocytes placed on a ribbed chip stretched out after two days and began to grow along the grooves of the hydrogel. Moreover, they actively formed contacts between the layers of cells, which gave the whole culture a structure similar to that of a real heart muscle (left). At the same time, the cells cultured on a smooth hydrogel surface remained small and practically did not form intercellular contacts (right). After a few more days, the cells grown on the structured surface, like a real heart muscle, began to conduct electric waves and contract in a strictly defined direction.
According to Levchenko, the most surprising thing for the authors was the fact that changing the nanorelief of the surface makes it possible to influence the functions and structure of the cultivated tissue. This demonstrates a high degree of "nanosensitivity" of cells, provided by their ability to fit snugly to the smallest surface curvatures. The results obtained indicate that the extracellular matrix is a powerful means of controlling cell growth at the nanoscale, and the reproduction of its properties will allow researchers to create fully functioning cardiac muscle tissue without the use of additional chemical signals.
The device of the chip and the experiments carried out using it are described in the preliminary on-line version of the Proceedings of the National Academy of Sciences in the article "Nanoscale cues regulate the structure and function of macroscopic cardiac tissue constructs" (in additional materials to the article there are videos with differently, depending on the structure of the surface, shrinking cardiomyocytes). The authors of the article believe that the new chip can be used to develop new methods of treatment and diagnosis of heart diseases.
Portal "Eternal youth" http://vechnayamolodost.ru according to ScienceDaily: Heart cells on lab chip display 'nanosense' that guides behavior.
22.12.2009