Tag Archives: artificial cells

Tractor beams for artificial cells

This particular piece has videos of cells moving around. I won’t be including all of them but they are weirdly fascinating. First, a May 14, 2018 news item on Nanowerk announces the latest in tractor beam news from the Imperial College London (ICL; UK),

Researchers have used lasers to connect, arrange and merge artificial cells, paving the way for networks of artificial cells that act like tissues.

The team say that by altering artificial cell membranes they can now get the cells to stick together like ‘stickle bricks’ – allowing them to be arranged into whole new structures.

Biological cells can perform complex functions, but are difficult to controllably engineer.

Artificial cells, however, can in principle be made to order. Now, researchers from Imperial College London and Loughborough University have demonstrated a new level of complexity with artificial cells by arranging them into basic tissue structures with different types of connectivity.

These structures could be used to perform functions like initiating chemical reactions or moving chemicals around networks of artificial and biological cells. This could be useful in carrying out chemical reactions in ultra-small volumes, in studying the mechanisms through which cells communicate with one another, and in the development of a new generation of smart biomaterials.

A May 14, 2018 ICL press release by Hayley Dunning , which originated the news item, provides more detail,

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 today 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

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.

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

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.

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.”

Here’s one of the videos that has been embedded with ICL press release,

You can see the whole series if you go to the May 14, 2018 ICL press release.

Here’s a link to and a citation for the paper,

Sculpting and fusing biomimetic vesicle networks using optical tweezers by Guido Bolognesi, Mark S. Friddin, Ali Salehi-Reyhani, Nathan E. Barlow, Nicholas J. Brooks, Oscar Ces, & Yuval Elani. Nature Communicationsvolume 9, Article number: 1882 (2018) doi:10.1038/s41467-018-04282-w Published: 14 May 2018

This paper is open access.

An entire chemistry lab (nanofactory) in a droplet

I love the blue in this image, which illustrates the thousand-droplets test, research suggesting the possibility of a nanofactory or laboratory within a droplet ,

Droplets with a diameter of only a few micrometers act as the reaction vessels for a complex oscillating reaction - Photo: Maximilian Weitz / TUM

Droplets with a diameter of only a few micrometers act as the reaction vessels for a complex oscillating reaction – Photo: Maximilian Weitz / TUM

A Feb. 19, 2014 news item on Azonano reveals more,

An almost infinite number of complex and interlinked reactions take place in a biological cell. In order to be able to better investigate these networks, scientists led by Professor Friedrich Simmel, Chair of Systems Biophysics and Nano Biophysics at the Technische Universitaet Muenchen (TUM) try to replicate them with the necessary components in a kind of artificial cell.

This is also motivated by the thought of one day using such single-cell systems for example as “nanofactories” for the production of complex organic substances or biomaterials.

All such experiments have so far predominantly worked with very simple reactions, however. NIM Professor Friedrich Simmel and his team have now for the first time managed to let a more complex biochemical reaction take place in tiny droplets of only a few micrometers in size. Together with co-authors from the University of California Riverside and the California Institute of Technology in Pasadena, USA, the scientists are presenting their findings in the current edition of Nature Chemistry.

The Feb. 18, 2014 TUM press release, which originated the news item, details the experiements,

Shaking once – investigating thousands of times

The experiment is conducted by putting an aqueous reaction solution into oil and shaking the mixture vigorously. The result is an emulsion consisting of thousands of droplets. Employing only a tiny amount of material, the scientists have thus found a cost-efficient and quick way of setting up an extremely large number of experiments simultaneously.

As a test system, the researchers chose a so-called biochemical oscillator. This involves several reactions with DNA and RNA, which take place repetitively one after the other. Their rhythm becomes visible because in one step two DNA strands bind to each other in such a way that a fluorescent dye shines. This regular blinking is then recorded with special cameras.

Small droplets – huge differences

In the first instance, Friedrich Simmel and his colleagues intended to investigate the principal behavior of a complex reaction system if scaled down to the size of a cell. In addition, they specifically wondered if all droplet systems displayed an identical behavior and what factors would cause possible differences.

Their experiments showed that the oscillations in the individual droplets differed strongly, that is to say, much stronger than might have been expected from a simple statistical model. It was above all evident that small drops display stronger variations than large ones. “It is indeed surprising that we could witness a similar variability and individuality in a comparatively simple chemical system as is known from biological cells”, explains Friedrich Simmel the results.

Thus, it is currently not possible to realize systems which are absolutely identical. This de facto means that researchers have to either search for ways to correct these variations or factor them in from the start. On the other hand, the numerous slightly differing systems could also be used specifically to pick out the one desired, optimally running set-up from thousands of systems.

Investigating complex biosynthetic systems in artificial cells opens up many other questions, as well. In a next step, Friedrich Simmel plans to address the underlying theoretical models: “The highly parallel recording of the emulsion droplets enabled us to acquire plenty of interesting data. Our goal is to use these data to review and improve the theoretical models of biochemical reaction networks at small molecule numbers.”

Here’s link to and a citation for the paper,

Diversity in the dynamical behaviour of a compartmentalized programmable biochemical oscillator by Maximilian Weitz, Jongmin Kim, Korbinian Kapsner, Erik Winfree, Elisa Franco, & Friedrich C. Simmel. Nature Chemistry (2014) doi:10.1038/nchem.1869 Published online 16 February 2014

This paper is behind a paywall.