'Liquid Lego' Nanodrops — Heartbeat on a chip?

The November 2007 Scientific American features an article by Gary Stix about a new technology in which water droplets encased in fat simulate cell membranes.

The dream: Simulate the pulsation of a heartbeat on a chip.

Here's the story.

A Simple Mimic — Water Droplets Encased In Fat Simulate Cell Membranes

A double layer of fat marks the property line that separates DNA, mitochondria, the endoplasmic reticulum and the rest of the elaborate internal machinery from everything that exists beyond the confines of a cell. Molecules of protein that poke through this lipid bilayer serve as communication channels for incoming and outgoing messages that regulate the body’s most basic activities.

Biologists have tried for decades to produce a simple model of the cell’s plasma membrane, particularly the openings to the outside world known as ion channels. The goal is not just academic. More than 60 ion-channel gene mutations have been linked to human diseases. Some drugs that target ion channels have achieved blockbuster status. Pharmaceutical companies could deploy such a model to simulate how new drugs interact with membrane proteins.

An ideal model has remained elusive. Some laboratories have focused on producing protocells — empty shells that are filled with cellular machinery that makes proteins or causes a fake cell to divide. Others have just created imitation cell membranes that simulate the electrical and chemical traffic at the cellular gateway. The most ambitious of these endeavors points toward a marriage of the work on protocells with membrane mimicry. It involves research at the University of Oxford and Duke University in which water droplets enveloped in a layer of fat come together to form bilayers into which membrane channels or pores can be inserted.

The droplets are manufactured by dissolving lipids in a small reservoir of oil. Water droplets measuring less than a millimeter across join the mix, causing the lipids to form a coating on the droplets of no more than half the thickness of a cell membrane. “These systems are very stable, like a robust soap bubble with a skin that’s a biological surface,” Matthew Holden, a postdoctoral fellow at the Oxford laboratory of chemist Hagan Bayley, where much of the research took place [see “Building Doors into Cells,” by Hagan Bayley; Scientific American, September 1997].

Dubbed “liquid Lego,” the droplets are intended to be a test bed for exploring the workings of not just a single cell membrane but an entire network of protocells. When a droplet joins with one of its neighbors, the two form the equivalent of a complete membrane. Ultimately, the team would like to engineer droplets with different characteristics, varying the pH of the water inside a droplet or the types of membrane channels used. Alternatively, different droplets may contain different drugs. The objective is to demonstrate how cells that constitute heart, brain or lung tissues communicate among themselves. “The new preparation of nanodrops holds enormous promise,” says Bob Eisenberg, chairman of biophysics and physiology at Rush University Medical Center in Chicago. “It will allow manipulation of ion channels in new ways; it will allow systems to be built from arrays of drops that show interesting properties.”

For the moment, simulating the pulsations of a heartbeat on a chip remains a dream, although the necessary tools are starting to come forth. In the June 16 online Journal of the American Chemical Society, Holden and his colleagues recount how they sent current through a chain of 16 droplets by plugging electrodes into various droplets along the network. They inserted bacterial pores (surrogates for ion channels) into the lipid protomembranes and also showed how electrodes could be used to add or remove droplets while keeping the network intact.

Two droplet experiments demonstrated the prospect of one day building autonomous systems that power themselves or make their own components. The paper describes a battery devised by infusing droplets with differing concentrations of ions and, separately, a current generated when droplets were infused with a membrane protein (bacteriorhodopsin) that causes protons to flow when exposed to green light.

The last unrealized step, of course, would be to insert DNA and organelles from a cell that could encode the desired ion channel from within the droplet. Then all scientists might have to do is just turn on the lights and watch the show.

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The caption for the photo at the top reads, "Liquid Lego: Fat-covered droplets snap together to form the initials for the University of Oxford, where these imitation cells, each of which holds 200 nanoliters of water, were first concocted."