For the first time, scientists have had a peak at the intricate workings of a cell from the inside. Miniscule tracking devices that resemble tiny spiders have been slipped into the interior of egg cells at the moment of fertilisation, giving a singular view of the processes that govern the beginning of development.
This work on one-cell embryos is set to shift our understanding of the mechanisms that underpin cellular behaviour in general, and may ultimately provide insights into what goes wrong in ageing and disease.
The research, led by Professor Tony Perry from the Department of Biology and Biochemistry at the University of Bath, involved injecting a silicon-based nanodevice together with sperm into the egg cell of a mouse. The result was a healthy, one-cell embryo containing a tracker.
The tiny devices behave a little like spiders, complete with eight highly flexible ‘legs’. The legs measure the ‘pulling and pushing’ forces exerted in the cell interior to a very high level of precision, thereby revealing the cellular forces at play and showing how intracellular matter rearranged itself over time.
The nanodevices are incredibly thin – similar to some of the cell’s structural components, and measuring 22 nanometres, making them approximately 100,000 times thinner than a pound coin. This means they have the flexibility to register the movement of the cell's cytoplasm as the one-cell embryo develops towards becoming a two-cell embryo.
“This is the first glimpse of the physics of any cell on this scale from within,” said Professor Perry. “It’s the first time anyone has seen from the inside how cell material moves around and organises itself.”
Why probe a cell’s mechanical behaviour?
The activity within a cell determines how that cell functions, explains Professor Perry. “The behaviour of intracellular matter is probably as influential to cell behaviour as gene expression – and probably influences gene expression,” he said.
Until now, however, this complex dance of cellular material has remained largely unstudied because it is so technically challenging. As a result, scientists have been able to identify the elements that make up a cell, but not how the cell interior behaves as a whole.
“From studies in biology and embryology, we know about certain molecules and cellular phenomena, and we have woven this information into a reductionist narrative of how things work, but now this narrative is changing,” said Professor Perry.
The narrative was written largely by biologists, who brought with them the questions and tools of biology. What was largely missing was physics. Physics asks about the forces driving a cell’s behaviour, and provides a top-down approach to finding the answer.
"We can now look at the cell as a whole, not just the nuts and bolts that make it,” said Professor Perry.
Mouse embryos were chosen for the study because of their relatively large size (they measure 100 microns, or 100-millionths of a metre, in diameter, compared to a regular cell which is only 10 microns [10-millionths of a metre] in diameter). This meant that inside each embryo, there was space for a tracking device.
The researchers made their measurements by examining video recordings taken through a microscope as the one-cell embryo developed.
“Sometimes the devices were pitched and twisted by forces that were even greater than those inside muscle cells,” said Professor Perry. “At other times, the devices moved very little, showing the cell interior had become calm. There was nothing random about these processes – from the moment you have a one-cell embryo, everything proceeds in a predictable way. The physics is programmed.”
The results add to an emerging picture of biology that suggests material inside a living cell is not static, but instead changes its properties in a pre-ordained way as the cell performs its function or responds to the environment. The work may one day have implications for our understanding of how cells age, or stop working as they should, which is what happens in disease.
The study is published in this month's issue of Nature Materials and involved a trans-disciplinary partnership between biologists, materials scientists and physicists based in the UK, Spain and the USA.