Ziapin2 molecules to stimulate skeletal muscle cells with light

A team of researchers from Istituto Italiano di Tecnologia (IIT) in Milan and Politecnico di Milano, coordinated by Guglielmo Lanzani, coordinator of Nanomaterials for Energy and Lifescience at IIT, has demonstrated that Ziapin2 molecules are able to control the contractile activity of skeletal muscle cells, which are responsible for the voluntary contraction of muscles, by means of light.

The Ziapin2 molecule, patented in 2018 in Europe, the United States and Japan by IIT and the Politecnico di Milano and first presented in Nature Nanotechnology in 2020, is a phototransducer, i.e., it absorbs light and transforms it into an electrical signal, and was conceived and synthesised in the laboratory coordinated by Chiara Bertarelli, full professor at Politecnico di Milano. 

The results of the study, published in the journal Nature Communications Biology, lay the foundations for implementing photostimulation combined with Ziapin2 as an alternative to the use of traditional electrodes for specific cases and pathologies, as this shows several advantages, including: greater versatility, since the light can be administered remotely with no contact; greater precision, due to high space-time selectivity; less invasiveness and toxicity.

The study was supported by funding from the Project of National Interest (PRIN) 'Membrane- targeted light-driven nanoactuators for neuro-stimulation'.

To demonstrate the feasibility of the new approach, the multidisciplinary team administered Ziapin2 to skeletal muscle cells grown in the laboratory (C2C12). This is an ideal cellular model for assessing the capacity of phototransducers, due to its negligible spontaneous contractile activity. In addition, this cellular model ensures that no animal models are used.

When cells which have been administered Ziapin2, are illuminated, the absorbed light translates into electricity that induces contractions.

The research team compared light stimulation with electrical stimulation and identified advantages from the use of photostimulation especially for long-termtreatment patients. Prolonged use of electrodes over time can lead to degradation of the patient's tissue and the electrodes themselves, resulting in a decrease in the effectiveness of the treatment.

To date, many patients suffering from neurodegenerative diseases such as Parkinson's, muscular pathologies, consequences of strokes or damage to the central nervous system, including loss of vision, cannot be treated with drug therapies, but they benefit from direct stimulation of muscle or nerve cells, which is traditionally carried out by means of electrodes, mostly metal ones, that transmit electric currents. 

Stimulation with light would lead to less cellular stress, as it allows us to stimulate a localised point, which is not possible using the general electric field of electrodes; it would reduce toxicity as different wavelengths can be used; and it would eliminate the need for contact, as light can be delivered remotely.

Because of these promising characteristics, photostimulation of cells could be used in the future especially in cardiology, muscle rehabilitation (functional stimulation), treatment of patients suffering from neuronal degeneration, as well as in a particular field, that of hybrid robots consisting of artificial and biological components. These robots can be used for fundamental studies, environmental exploration or medical and prosthetic applications, as they are totally bio-compatible.

The results we have obtained show that it is possible intervene on muscle tissue with precision and in a minimally invasive way by using light, assisting current techniques in the treatment of certain musculoskeletal pathologies.

Guglielmo Lanzani, Researcher at IIT, explains.

Targeting the cell membrane by the molecular design of phototransducers is an innovative approach. Ziapin2 has once again demonstrated its effectiveness and potential in photoinduced stimulation of cells, with an increasingly broad spectrum of applications in the medical field and great potential in the development of hybrid robots

comments Chiara Bertarelli from the Department of Chemistry, Materials and Chemical Engineering ‘Giulio Natta’ at Politecnico di Milano.

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Cover image: Videoframe of a cell to be analyzed. Credits: Istituto Italiano di Tecnologia - © IIT