Mini Tractor Beams Help Arrange Artificial Cells into Tissue Structures

Tractor beams and stickle bricks

Cells are the basic units of biology, which are capable of working together as a collective when arranged into tissues. In order to do this, cells must be connected and be capable of exchanging materials with one another.

The team were able to link up artificial cells into a range of new architectures, the results of which are published in Nature Communications.

The artificial cells have a membrane-like layer as their shell, which the researchers engineered to ‘stick’ to each other. In order to get the cells to come close enough, the team first had to manipulate the cells with ‘optical tweezers’ that act like mini ‘tractor beams’ dragging and dropping cells into any position. Once connected in this way the cells can be moved as one unit.

Lead researcher Dr Yuval Elani, an EPSRC Research Fellow from the Department of Chemistry at Imperial, said: “Artificial cell membranes usually bounce off each other like rubber balls. By altering the biophysics of the membranes in our cells, we got them instead to stick to each other like stickle bricks.

“With this, we were able to form networks of cells connected by ‘biojunctions’. By reinserting biological components such as proteins in the membrane, we could get the cells to communicate and exchange material with one another. This mimics what is seen in nature, so it’s a great step forward in creating biological-like artificial cell tissues.”

Building up complexity
 

Credit: Imperial College London

The video above shows one cell being dragged by the laser beam towards another cell, and the two cells’ membranes sticking together.

The team were also able to engineer a ‘tether’ between two cells. Here the membranes are not stuck together, but a tendril of membrane material links them so that they can be moved together.

A fluorescing cell (brighter white outline) dragged towards a non-fluorescing cell, and a tether strung between them. The non-fluorescing cell is then dragged to the left, pulling the fluorescing cell with it.

The video above shows a fluorescing cell (brighter white outline) dragged towards a non-fluorescing cell, and a tether strung between them. The non-fluorescing cell is then dragged to the left, pulling the fluorescing cell with it.

Once they had perfected the cell-sticking process, the team were able to build up more complex arrangements. These include lines of cells, 2D shapes like squares, and 3D shapes like pyramids. Once the cells are stuck together, they can be rearranged, and also pulled by the laser beam as an ensemble.
 

Credit: Imperial College London

The video above shows four artificial cells brought together first as a line, then a square, then a pyramid with one cell on the top. The whole structure is then dragged together by the laser.

Finally, the team were also able to connect two cells, and then make them merge into one larger cell. This was achieved by coating the membranes with gold nanoparticles.

When the laser beam at the heart of the ‘optical tweezer’ technology was concentrated at the junction between the two cells, the nanoparticles resonated, breaking the membranes at that point. The membrane then reforms as a whole.

The video above shows two cells sticking together, with a laser shone at the interface between them.

Credit: Imperial College London

The cells then merge into one larger cell.

Merging cells in this way allowed whatever chemicals they were carrying to mix within the new, larger cell, kicking off chemical reactions. This could be useful, for example, for delivering materials such as drugs into cells, and in changing the composition of cells in real time, getting them to adopt new functions.

Professor Oscar Ces, also from the Department of Chemistry at Imperial, said: “Connecting artificial cells together is a valuable technology in the wider toolkit we are assembling for creating these biological systems using bottom-up approaches.

“We can now start to scale up basic cell technologies into larger tissue-scale networks, with precise control over the kind of architecture we create.”

-