Each week, staff writer Paul Wood interviews a different high-tech difference-maker. This week, meet University of Illinois mechanical science and engineering Professor TAHER SAIF, who works on the mechanics of living cells, as well as nanoscale materials. In 2014, his lab developed the first autonomous, self-propelled biohybrid swimming robot at sub-millimeter scale. It was powered by beating cardiac muscle cells from rats. Now, he has led a team to take the first step toward intelligent biohybrid swimmers by incorporating neurons on board.
Tell us what’s different about your biobots.
University of Illinois’ College of Engineering is the home of the new invention of biological machines. Unlike conventional machines that need assembly, these machines self-emerge from interactions between living cells and engineered scaffolds. Rashid Bashir and I have jointly pioneered the field by developing a series of self-propelled biohybrid walking biobots and swimmers.
What is the latest innovation?
The recent biohybrid swimmer paved the way towards intelligent machines. In contrast to only muscle cells that propelled the previous biorobots, this new generation brings neurons, the new players, on board. The neurons spontaneously send out long cables of axons towards the muscle tissues that wrap around the two tails of the swimmer. These axons form junctions with the muscles, just like our neurons form neuro-muscular junctions with our muscles that allow us to walk and talk.
Neurons also form a network among themselves. So the neurons and muscles emerge into a self-assembled integrated system, through as-yet-unknown crosstalk between each other at multiple length and time scales. This can be viewed development in vitro. The neurons stimulate the muscle by firing in a periodic fashion. The muscles contract and bend the tails, like the flagella of bacteria, which propels the swimmer forward.
Being driven by neurons, this new swimmer opens the possibility of imbuing them with training, sensing, memory and learning in the future. For example, the neurons may sense the environment, and when a threshold is exceeded, they may fire on demand and propel the swimmer in the desired direction.
How does light pay into this scenario?
The neurons we used are opgenetic, i.e., they are light sensitive. In response to light exposure, they fire. This allowed us to test the swimmers for their light sensitivity. When we shine light, the neurons fire synchronously and periodically. In response, the muscles contract periodically and the swimmer swims.
How did the ability come about?
The neurons are modified to express an ion channel that responds to light with a specific wavelength. When light is shined, these channels open and allow ion transport, which leads to the firing of the neurons.
Who else is on your team?
The research team includes graduate student Onur Aydin, graduate student Xiastian Zhang, Professor Mattia Gazzola and graduate student Gelson J. Pagan-Diaz.
What sort of cell tissue did you use?
We used neurons derived from mouse embryonic stem cells and skeletal muscle cells. The muscle cells interact with each other and form a muscle tissue, which serves as the actuator for the swimmer.
Why did you decide to model the bots on sperm? Do they have an easy-to-mimic movement?
Our 2014 swimmer mimicked a sperm. This current swimmer has two tails originating from the head where the neurons are. The muscle wraps around the tails near their base and pulls them towards each other when stimulated. This two-tailed design generates much higher propulsive force compared to a one-tailed swimmer predicted by our computational model carried out by Professor Gazzola’s lab.
Do your new bots sense the environment?
They sense only light at this point. But the neurons can be programmed to sense other environmental signals as well.
What kind of tissue is used?
We do not use any pre-formed tissue. We put the cells mixed with extracellular matrix (ECM), collagen and Matrigel. The cells interact with each other and the ECM to form the muscle tissue all by themselves. Similarly, the neurons interact with each other and form the neural network. The neurons and the muscle also interact with each other to form the neuro-muscular junctions. Professor Gazzola used computational models to find physical attributes for the fastest and most efficient swimming.
How can this research lead to more biohybrid neuromuscular designs?
This swimmer serves as the first platform demonstrating the integration of neurons and muscles where muscles can generate force and carry out mechanical work when stimulated by the neurons. This will allow to design a variety of biohybrid machines, including walkers and swimmers with programmable neuronal networks that can sense the environment and stimulate the muscles as needed to steer the motion of the biobots, and in vitro neuro-muscular units that can allow us to study the effect of exercise on neuronal function as well as explore neuro-muscular disease.
No two bots are the same. Why is that?
Each biobot emerges itself through interactions between multiple types of cell (neurons and muscle cells in our case). The cells also interact with the engineered scaffold that hosts them. The scaffold only guides their interaction. These living machines are not manufactured in the conventional way, where components are assembled in an identical way. Hence two biobots are not identical as two cars are or two TVs are.
Who supported your research?
The National Science Foundation Science and Technology Center – Emergent Behavior for Integrated Cellular Systems and NSF’s Emergent Frontiers in Research and Innovation grant supported this research.
Have you ever make any mistakes you’ve been able to learn from?
Yes, initially we had difficulty in forming muscle tissues of the swimmers. We learned that tissues cannot form when the cell density in the ECM mixture is below a critical value, or the space between the cells in the ECM is above a critical distance.
TECH TIDBITS ... from TAHER SAIF
Do you have a favorite thing to follow on social media, or an app you really like? I am not on any social media.
What are you reading right now? I love to read non-fiction books, poems and philosophical writings. I just finished reading the book “Bad Blood,” by John Carreyrou. The philosophical writings of Rumi (Jalal ad-Din Muhammad Rumi), the 13th century Persian poet, are part of my everyday reading.
Do you have an entrepreneur hero? Muhammad Yunus, who introduced social banking, microcredit and microfinance. He is the founder of Grameen Bank.