Revolutionizing Drug Design with Tiny Light-Activated Machines

Calcium signaling is a key mechanism by which cells “talk” to each other to coordinate vital biological processes such as immune activation, muscle contraction, hormone release, nerve firing, and digestion.

In a recent study published in Natural Nanotechnologyresearchers from Paddy University revealed a powerful new method for directing cellular activity by using light-activated molecular machinery to generate calcium wave signals between cells.

People with heart difficulties, digestive problems, and other conditions can benefit from enhanced therapy with the help of this technology.

Most of the drugs developed to date use chemical binding forces to activate specific signaling cascades in the body. This was the first demonstration that, instead of chemical force, you can use mechanical force—induced, in this case, by a single molecule nanomachine—to do the same, which opened a new chapter in drug design.

Jacob Beckham, Lead Author of the Study and Graduate Student, Rice University

To trigger a calcium signaling response in smooth muscle cells, researchers used small molecule actuators that rotate when triggered by visible light.

Many major muscles of the human body are not under conscious control: Smooth muscle tissue lines the veins and arteries, regulating blood pressure and circulation; Smooth muscle lines the lungs and intestines, and is involved in digestion and respiration.

The ability to intervene in this process with mechanical stimuli at the molecular level can be game-changing.

Beckham has shown that we can control, for example, cell signaling in cardiac muscle, which is very exciting.

James Tour, TT and WF Chao Professor of Chemistry, Rice University

He added, “If you stimulate just one cell in the heart, it will spread the signal to neighboring cells, which means you can target, fine-tuned molecular control over heart function and possibly reduce arrhythmias..”

The molecular machinery, activated by quarter-second pulses of light, allows scientists to manipulate calcium signaling in cell cultures of cardiac myocytes, forcing quiescent cells to fire.

Beckham stated, “The molecule essentially functions as a nano-defibrillator, getting these cardiac muscle cells to start beating.”

The capacity to regulate cell-to-cell communication in muscle tissue may prove useful for the treatment of various diseases characterized by dysfunctional calcium signaling.

Tour added, “Many crippled people have major digestive problems. It would be a big deal if you could solve this problem by causing those relevant muscles to work without any kind of chemical intervention.”

Freshwater polyps, or Hydra vulgaris, undergo whole-body contractions as a result of activation of molecular-sized devices of the same calcium-based cellular signaling processes in living organisms.

“This is the first example of using a molecular machine and using it to control an entire functioning organism”Tours added.

The type and strength of mechanical stimulation affect cellular response: In contrast to slower speeds and multidirectional rotation, fast, non-unidirectional rotating molecular machinery generates calcium wave signals between cells.

Furthermore, the cellular reaction strength can be changed by varying the light intensity.

The tour further stated, “It is a mechanical action on the molecular scale. These molecules rotate at a rate of 3 million rotations per second, and because we can adjust the duration and intensity of the light stimulus, we have precise spatiotemporal control over this very common cellular mechanism.”

Tour’s lab has shown in previous research that light-activated molecular machines can be used to fight cancer cells, infectious bacteria resistant to antibiotics, and harmful fungi.

Beckham noted, “This work extends the capabilities of these molecular machines in different directions. What I love about our lab is that we are fearless when it comes to being creative and pursuing projects in ambitious new directions. We are currently working to develop a light-activated machine with an even better depth of penetration to really actualize the potential of this research. We also wanted to gain a better understanding of the molecular-scale actuation of biological processes.”

DEVCOM Army Research Laboratory (Cooperative Agreement W911NF-18-2-0234), Robert A. Welch Foundation (C-2017-20190330), National Science Foundation Graduate Research Fellowship Program, Discovery Institute, and European Union Horizon 2020 (Marie Grant Agreement) Sklodowska-Curie 843116) provided funding for this research.

Molecular motor-induced calcium wave oscillation and beating motion in cardiac myocyte cellsPlay