Rescue rafts are a lifesaver, although other types of rafts may put our lives in danger: that is the case with 'lipid rafts', which are exploited by coronaviruses to attack human cells. An interdisciplinary research group coordinated by the University of Trento and the University of Napoli - Federico II set out to understand what happens when a virus jumps on this type of raft to invade a cell.
To penetrate the human cell, the virus tricks the cell membrane that surrounds it. The membrane has a crucial role, because it ensures the regular functioning of the cell which is essential for tissue growth and development and organ functionality. When a virus sneaks into a cell pretending to be something friendly - a ligand, namely a molecule that binds to a chemically affine receptor and forms a complex capable to cause a cellular response - the membrane responds by creating localized thickened zones, called 'lipid rafts'. Indeed, that is where receptors find favourable sites for binding. Indeed, receptors must change their configuration as they bind to their ligand and this can be done more easily across suitable stress-relieved zones of the cell membrane, namely on the rafts. Also, these thickenings turn out to be energetically favourable for the system, thereby becoming entryways for viruses and ligands in general. The researchers adopted a mechanobiological approach to explain how the microstructural properties of the membrane interact with biochemical processes to form lipid rafts.
The study may suggest new strategies to limit virus attacks and prevent or combat diseases like Sars and Covid-19 based on biomedical and engineering principles.
The research was conducted by Luca Deseri and Nicola Pugno, professors of the group of Mechanics of solids and structures of the Department of Civil, Environmental and Mechanical Engineering of the University of Trento, and by the team of Massimiliano Fraldi, professor of the Department of Structures for Engineering and Architecture of the University of Napoli- Federico II, in collaboration with researchers at Carnegie Mellon University and at the University of Pittsburgh, in the USA, and with the universities of Palermo and Ferrara, where experiments were carried out.
Deseri explained how viruses attack cells: "The cell membrane regulates the transport of nutrients and the removal of waste products, and acts as a barrier to keep toxic substances and pathogens, including viruses, out. Viruses SARS-CoV-1 and SARS-CoV-2, which caused the current Covid-19 pandemic, trick the membrane by showing specific anti-receptors that look like ligands, to which the cell's receptors usually bind to, activating localized thickenings in the membrane, the 'lipid rafts', which then are used by viruses to enter the cell".
The findings contribute to the ongoing discussion on the diseases caused by coronaviruses of the SARS-Severe Acute Respiratory Syndrome type. "This study may suggest new strategies to identify innovative therapeutic approaches to prevent or fight the virus by integrating biomedical and mechanical knowledge", Deseri, Pugno and Fraldi remarked.
About the article - The article "Mechanobiology predicts raft formations triggered by ligand-receptor activity across the cell membrane" was written for the Journal of the Mechanics and Physics of Solids by Angelo R. Carotenuto, Laura Lunghi, Valentina Piccolo, Mahnoush Babaei, Kaushik Dayal, Nicola M. Pugno, Massimiliano Zingales, Luca Deseri (corresponding author) and Massimiliano Fraldi. It will appear in the August (volume 141, 2020, 103974). The online version is already available in Open Access.
The work has also been included in a collection by Elsevier whose purpose is to disseminate articles on Covid-19.
A related research with a specific focus on covid-19 will be submitted as part of a special issue (edited by Nicola Pugno) on the pandemic on the international Journal "Frontiers", in the Materials section.