Light-activated molecular machines make cells ‘talk’: Mechanical control of vital cellular processes could revolutionize drug design

One of the main ways cells «talk» to each other to coordinate essential biological activities such as muscle contraction, hormone release, nerve cell activation, digestion, and immune activation is through calcium signal.

According to a new study published in the American Journal of Science and Technology, Rice University scientists used light-activated molecular machines to trigger calcium wave signals between cells. cells, revealing a powerful new strategy for controlling cellular activity. Nature nanotechnology. This technology could lead to improved treatments for people with heart problems, digestive problems, etc.

«Most of the drugs developed to date use chemical binding forces to control a chain,» said Jacob Beckham, a graduate student in chemistry and lead author of the study. specific signals in the body. «This is the first demonstration that, instead of chemical force, you can use mechanical force – in this case caused by a single-molecule nanomachine – to do the same thing, which opens a whole chapter new 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 lack conscious control over many vital organs in the body: The heart is an involuntary muscle, and there are smooth muscle tissues lining our veins and arteries, controlling blood pressure. and circulation; Smooth muscle forms sugars for our lungs and intestines and is involved in digestion and respiration. The ability to interfere with these processes with mechanical stimulation at the molecular level could be a game changer.

«Beckham has demonstrated that we can control cell signaling in the body,» said James Tour, Rice’s TT and WF Chao Professor of Chemistry and professor of materials science and nanoengineering. heart, for example, this is really exciting.»

“If you stimulate just one cell in the heart, it sends a signal to the neighboring cells, which means you can target, control the molecule that is tunable for that,” says Tour. with cardiac function and may reduce arrhythmias”.

Triggered by pulses of light lasting a quarter of a second, the molecular machines allow scientists to control calcium signaling in cardiomyocyte cultures, causing dormant cells to activate. .

«The molecules essentially act as nano-defibrillators, causing these heart muscle cells to start beating,» Beckham said.

The ability to control cell-to-cell communication in muscle tissue could be useful for the treatment of a variety of diseases characterized by dysfunctional calcium signaling.

«A lot of people with paralysis have serious digestive problems,» says Tour. «It would be a big deal if you could alleviate these problems by getting those muscles involved without any chemical intervention.»

The molecular-sized devices activated the same calcium-based cell signaling mechanism in a living organism, causing whole-body contraction in a freshwater polyp, aka Hydra Vulgaris .

“This is the first example of taking a molecular machine and using it to control the whole body in action,” says Tour.

Cell response varies based on the type and intensity of mechanical stimulation: Fast, one-way spinning molecular machines generate calcium wave signals between cells, while slower speeds and multidirectional rotations not.

Furthermore, adjusting the light intensity allows the scientists to control the intensity of the cell’s response.

“This is mechanical action at the molecular scale,” says Tour. «These molecules rotate at 3 million revolutions per second, and because we can adjust the duration and intensity of the light stimulus, we have precise space-time control over the body.» this very common cell mechanism.»

The Tour Lab has shown in previous research that light-activated molecular machines can be deployed to fight antibiotic-resistant infectious bacteria, cancer cells and pathogenic fungi.

«This work extends the capabilities of these molecular machines in another direction,» Beckham said. «What I like about our lab is that we are fearless when it comes to creativity and pursuing projects in ambitious new directions.»

«We’re currently working on developing light-activated machines with better penetration depths to really realize the potential of this research. We’re also looking to better understand the operation. at the molecular scale of biological processes.»

The research was supported by the Discovery Institute, the Robert A. Welch Foundation (C-2017-20190330), the National Science Foundation Graduate Research Fellowship Program, the DEVCOM Military Research Laboratory (Agreement) partnership W911NF-18-2-0234) and Horizon 2020 of the European Union (Marie Sklodowska-Curie Grant Agreement 843116).

#Lightactivated #molecular #machines #cells #talk #Mechanical #control #vital #cellular #processes #revolutionize #drug #design

Deja un comentario