Researchers mechanically divide liposomes in the lab

Growth and division are the fundamental characteristics of living cells. Yet the basic components essential for the functioning of these life processes remain shrouded in mystery. To answer this question, Siddharth Deshpande, a postdoctoral researcher at Cees Dekker’s lab at Delft University of Technology in the Netherlands dreams of constructing an autonomous, artificial cell using a bottom–up approach. Dr. Deshpande and team have now achieved a part of their goal by mechanically dividing liposomes, which are compositional equivalents of cell envelopes.

All living cells are enclosed in a lipid envelope. Thus, a liposome, which is a lipid bubble filled with water, is the simplest mimic of a living cell. Generating pure liposomes in a controlled fashion in the lab is not simple. To achieve this goal, Dr. Deshpande designed tiny fluid chambers with dimensions in the order of one-millionth of a metre to form stable liposomes. He reported this bubble-blowing method called octanol-assisted liposome assembly (OLA) in Nature in 2016 and in Nature Protocols in 2018.

The team’s next mission was to split these liposomes into ‘daughter’ liposomes. In the past, researchers have used different methods to divide liposomes. However, all these methods suffered from leaky daughter liposomes and asymmetric splitting.

Simple approach

In their latest study, published in ACS Nano journal, he kept the approach simple. “I thought why not collide them [liposomes] against a sharp wall inside the chamber to break them in two,” he said. He designed a wedge in the microfluidic chamber that physically blocked the newly formed liposomes as they progressed down the channel. By adding a fluorescent dye to the water inside the liposomes, the researchers visualised their fate using a microscope.

Although the technique sounds simple, the journey was not devoid of challenges. Splitting any sphere into multiple stable ones poses an inherent issue: the smaller spheres have a larger surface area to volume ratio than the parent sphere.

This means that either the surface area of the liposomes had to be increased or their volume had to be decreased to compensate for the change in surface area to volume ratio after division. The team overcame this issue by exploiting the fact that the liposome membrane permits passage of water. They flushed in a high-salt solution in the chamber to create an osmotic pressure difference. Consequently, the liposome exuded water with a resultant reduction in its volume.

“Combining growth and division would be truly fantastic,” said Deshpande regarding their plans of creating a truly autonomous artificial cell. Achieving the same would be interesting from a synthetic biology perspective and could further the understanding of cellular function.

(The author is a freelance science writer.)