August 14, 2023 ─ Researchers at the Hebrew University of Jerusalem (HU) and Shiv Nadar University in India have found that Cytochrome P450, an enzyme essential for the metabolism of many drugs, also acts as a soft 4-D robot that senses and responds to stimuli in a living organism.

The findings, published in Trends in Chemistry, indicate new avenues in soft robotics research as 4-D materials gain significance. These materials, such as hydrogels produced through 3-D printing, resemble enzymes in their ability to sense and induce changes. The implications of this discovery extend beyond the realm of biology and chemistry, potentially revolutionizing fields like artificial intelligence design and self-evolving polymers/gels synthesis.

Cytochromes P450 (CYP450s) play a crucial role in various biological processes. They are particularly prominent in the metabolism of drugs and xenobiotics. The researchers’ simulations demonstrated that CYP450s act as 4-D nanomachines which have the ability to sense and respond to stimuli in “living matter.”

“We have discovered that CYP450s act as soft-robot machines in ‘living matter,’ displaying a remarkable sensing and response-action capability,” stated Prof. Sason Shaik, co-lead researcher and Emeritus Professor of Chemistry, Institute of Chemistry at Hebrew University. “This is an exciting revelation, and we believe that similar mechano-transduction mechanisms of soft-impact cues might be at work in other soft robot machines in nature.”

A biological nanomachine is a macromolecular machine commonly found within a cell, which frequently performs tasks essential for life. The enzyme’s ability to function in a restricted space, its strategic residue placements, and its channels of access allow it to act as a sensor, which makes it a soft 4-D robot. Thus, CYP450s, and all biological nanomachines present in “living matters” are essentially soft 4-D robots.

“We are entering an exciting era for chemistry, where soft robotics and intelligent design of nanomachines can lead to unprecedented advancements,” says Dr. Kshatresh Dutta Dubey, co-researcher of the study. “Future researchers may witness the creation of self-evolving polymers and perpetual nanomachines capable of synthesizing new molecules at will.”