(Nanowerk News) One of the main ways cells “talk” to each other to coordinate important biological activities such as muscle contraction, hormone release, nerve firing, digestion, and immune activation is through calcium signaling.
Rice University scientists have used light-activated molecular machinery to trigger calcium wave signals between cells, revealing a powerful new strategy for controlling cellular activity, according to a new study published in Natural Nanotechnology (“Molecular machinery stimulates calcium waves between cells and causes muscle contraction”). This technology could lead to better care for people with heart problems, digestive problems, and more.
“Most of the drugs developed to date use chemical binding forces to drive specific signaling cascades in the body,” said Jacob Beckham, a chemistry graduate student and lead author of the study. “This is the first demonstration that, instead of a chemical force, you can use a mechanical force ⎯ induced, in this case, by a single molecule nanomachine ⎯ to do the same thing, which opens a new chapter in drug design.”
The scientists used small molecule-based actuators that rotate when stimulated by visible light to induce a calcium signaling response in smooth muscle cells.
We have no conscious control over many of the important muscles in our bodies: The heart is an involuntary muscle, and there is smooth muscle tissue lining our veins and arteries, which controls blood pressure and circulation; Smooth muscles line our lungs and intestines and are 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,” said James Tour, Rice’s TT and WF Chao Professor of Chemistry and a professor of materials science and nanoengineering.
“If you stimulate just one cell in the heart, it will propagate the signal to neighboring cells, which means you can target, fine-tuned molecular control over heart function and possibly reduce arrhythmias,” says Tour.
Activated by pulses of light for a quarter of a second, the molecular machine allows scientists to control calcium signaling in cell cultures of cardiac myocytes, causing dormant cells to light up.
“These molecules basically function as nano-defibrillators, getting these heart muscle cells to start beating,” said Beckham.
The ability to control cell-to-cell communication in muscle tissue could be useful for the treatment of various diseases characterized by dysfunction of calcium signaling.
“Many people who are paralyzed have severe digestive problems,” says Tour. “It would be a big deal if you could solve this problem by causing the relevant muscles to work without any kind of chemical intervention.”
Molecular-sized devices activate the same calcium-based cellular signaling mechanisms in living organisms, causing whole-body contractions in freshwater polyps, or Hydra vulgaris.
“This is the first example of taking a molecular machine and using it to control a whole functioning organism,” said Tour.
Cellular responses vary with the type and intensity of mechanical stimulation: Fast, asynchronously rotating molecular machinery generates signals of calcium waves between cells, whereas slower speeds and multidirectional rotation do not.
Additionally, adjusting the light intensity allows scientists to control the strength of the cellular response.
“This is a mechanical action on a molecular scale,” said Tour. “These molecules rotate at 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 machinery can be used against antibiotic-resistant infectious bacteria, cancer cells, and pathogenic fungi.
“This work extends the capabilities of this molecular machine in a different direction,” said Beckham. “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 on developing a light-activated machine with a better depth of penetration to really actualize the potential of this research. We also want to gain a better understanding of the molecular-scale actuation of biological processes.”