This is one in a series presenting news on technology and innovation, made possible with generous support from the Lemelson Foundation.
A new set of tools can pull individual molecules out of a living cell without killing it.
Think of it like a set of tweezers for use in the world’s smallest game of “Operation.”
Normally, sampling what’s in a cell requires breaking it open. “You basically kill the cell to get access,” says Orane Guillaume-Gentil. She did not work on the new device. This microbiologist at ETH Zurich in Switzerland is, however, familiar with the idea. With older tools, she points out, “It’s not possible to look at one cell and follow it over time.” It would be dead after the first look.
Because the new technique is so gentle, it can be used on the same cell over and over. That could show how a cell responds to growth or to things in its environment. And it might help people better understand how healthy cells work, and what goes wrong inside sick cells.
The researchers used their tweezers to extract molecules from different types of cells. First the team stained its cells with dyes. These glowed when the dyes glommed onto particular targets, such as DNA. Those target molecules would now stand out when researchers viewed them under a microscope. And that helped them guide their tweezers to extract the desired substance.
The researchers have removed DNA from human bone-cancer cells. They also entered human artery cells to nab messenger RNA. It’s a type of molecule that holds the instructions for building proteins. Extracting this mRNA from two different spots in a single cell, one hour apart, confirmed that the tweezers could be used to sample a cell more than once.
Joshua Edel is a chemist at Imperial College London in England. Key to his group’s new tool is a sharp, glass rod. Its thin tip is less than 100 nanometers across. That’s about a tenth the diameter of a red blood cell. At the end of this rod are two electrodes. Each is made of a carbon-based material, such as graphite.
When Edel’s team applies an electric voltage to the tweezers, a powerful electric field develops around the electrodes. This attracts and traps small molecules within about 300 nanometers of the rod’s tip. Once in this electric net, molecules stay put until the voltage is turned off. Only then can the molecules drift away.
And these new tools can retrieve cargo bigger than a single molecule. For instance, mitochondria (My-toh-KON-dree-uh) are big structures in cells that convert nutrients into energy. Edel’s team used its nanotweezers to remove mitochondria from the nerve cells found in mouse brains.
So far, the researchers have only used their tweezers to operate on cells in petri dishes. But Edel says his team plans to test its pluckers on cells living inside growing tissues.
They described their nanotweezers online December 3 in Nature Nanotechnology.
This tool is “very powerful,” says Pak Kin Wong. He’s a biomedical engineer at Pennsylvania State University, in State College. Indeed, he notes, the new tool should make it possible to get a more detailed view of what goes on inside cells. For instance, plucking proteins and other stuff from different parts of a cell might highlight what role each plays.
Alexandra-Chloe Villani works in Cambridge, Mass. There, she studies genomics and immunology at Massachusetts General Hospital and the Broad Institute of MIT and Harvard. She believes these gentle tools might one day help in projects like the Human Cell Atlas. It aims to create unique “ID” cards for each type of cell in the human body. Each ID would describe how a particular type of cell works.
Sampling DNA from different cells might help researchers also search for random changes in genes known as mutations, Edel says. Those mutations might underlie different diseases.
Monitoring the molecular makeup of cells over time also could reveal how cells are affected by illnesses or respond to new drugs, adds Guillaume-Gentil.
artery Part of the body’s circulation system. There are several. Each is a major tube running between the heart and blood vessels that will move blood to all parts of the body.
biomedical engineer An expert who uses science and math to find solutions to problems in biology and medicine; for example, they might create medical devices such as artificial knees.
cancer Any of more than 100 different diseases, each characterized by the rapid, uncontrolled growth of abnormal cells. The development and growth of cancers, also known as malignancies, can lead to tumors, pain and death.
cell The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall. Depending on their size, animals are made of anywhere from thousands to trillions of cells. Most organisms, such as yeasts, molds, bacteria and some algae, are composed of only one cell.
develop To emerge or come into being, either naturally or through human intervention, such as by manufacturing. (in biology) To grow as an organism from conception through adulthood, often undergoing changes in chemistry, size and sometimes even shape.
diameter The length of a straight line that runs through the center of a circle or spherical object, starting at the edge on one side and ending at the edge on the far side.
DNA (short for deoxyribonucleic acid) A long, double-stranded and spiral-shaped molecule inside most living cells that carries genetic instructions. It is built on a backbone of phosphorus, oxygen, and carbon atoms. In all living things, from plants and animals to microbes, these instructions tell cells which molecules to make.
electric field A region around a charged particle or object within which a force would be exerted on other charged particles or objects.
electrode A device that conducts electricity and is used to make contact with non-metal part of an electrical circuit, or that contacts something through which an electrical signal moves.
engineer A person who uses science to solve problems. As a verb, to engineer means to design a device, material or process that will solve some problem or unmet need.
environment The sum of all of the things that exist around some organism or the process and the condition those things create. Environment may refer to the weather and ecosystem in which some animal lives, or, perhaps, the temperature and humidity (or even the placement of things in the vicinity of an item of interest).
extract (v.) To separate one chemical (or component of something) from a complex mix.
field (in physics) A region in space where certain physical effects operate, such as magnetism (created by a magnetic field), gravity (by a gravitational field), mass (by a Higgs field) or electricity (by an electrical field).
gene (adj. genetic) A segment of DNA that codes, or holds instructions, for a cell’s production of a protein. Offspring inherit genes from their parents. Genes influence how an organism looks and behaves.
graphite Like diamond, graphite (the substance found in pencil lead) is a form of pure carbon. Unlike diamond, graphite is very soft. The main difference between these two forms of carbon is the number and type of chemical bonds between carbon atoms in each substance.
immunology The field of biomedicine that deals with the immune system. A doctor or scientist who works in that field is known as an immunologist.
messenger RNA A type of genetic material that is copied from DNA. It carries the instructions for building a cell’s proteins.
microbiology The study of microorganisms, principally bacteria, fungi and viruses. Scientists who study microbes and the infections they can cause or ways that they can interact with their environment are known as microbiologists.
microscope An instrument used to view objects, like bacteria, or the single cells of plants or animals, that are too small to be visible to the unaided eye.
mitochondria (sing. mitochondrion) Structures in all cells (except bacteria and archaea) that break down nutrients, converting them into a form of energy known as ATP.
molecule An electrically neutral group of atoms that represents the smallest possible amount of a chemical compound. Molecules can be made of single types of atoms or of different types. For example, the oxygen in the air is made of two oxygen atoms (O2), but water is made of two hydrogen atoms and one oxygen atom (H2O).
mutation (v. mutate) Some change that occurs to a gene in an organism’s DNA. Some mutations occur naturally. Others can be triggered by outside factors, such as pollution, radiation, medicines or something in the diet. A gene with this change is referred to as a mutant.
nanotechnology Science, technology and engineering that deals with things and phenomena at the scale of a few billionths of a meter or less.
nerve A long, delicate fiber that transmits signals across the body of an animal. An animal’s backbone contains many nerves, some of which control the movement of its legs or fins, and some of which convey sensations such as hot, cold or pain.
nutrient A vitamin, mineral, fat, carbohydrate or protein that a plant, animal or other organism requires as part of its food in order to survive.
online (n.) On the internet. (adj.) A term for what can be found or accessed on the internet.
petri dish A shallow, circular dish used to grow bacteria or other microorganisms.
protein A compound made from one or more long chains of amino acids. Proteins are an essential part of all living organisms. They form the basis of living cells, muscle and tissues; they also do the work inside of cells. Among the better-known, stand-alone proteins are the hemoglobin (in blood) and the antibodies (also in blood) that attempt to fight infections. Medicines frequently work by latching onto proteins.
random Something that occurs haphazardly or without reason, based on no intention or purpose.
red blood cell Colored red by hemoglobin, these cells move oxygen from the lungs to all tissues of the body. Red blood cells are too small to be seen by the unaided eye.
tissue Made of cells, it is any of the distinct types of materials that make up animals, plants or fungi. Cells within a tissue work as a unit to perform a particular function in living organisms. Different organs of the human body, for instance, often are made from many different types of tissues.
unique Something that is unlike anything else; the only one of its kind.
voltage A force associated with an electric current that is measured in units known as volts. Power companies use high-voltage to move electric power over long distances.