Publication 20-CNA-012
Mechanobiology Predicts Raft Formations Triggered By Ligand-Receptor Activity Across The Cell Membrane
A. R. Carotenuto
Department of Structures for Engineering and Architecture
University of Napoli "Federico II"
Italy
angelorosario.carotenuto@unina.it
L. Lunghi
Smiling International School (formerly at the Department of Life Sciences and Biotech)
University of Ferrara
Italy
lnglra1@unife.it
V. Piccolo
Department of Civil, Environmental and Mechanical Engineering
University of Trento
Italy
valentina.piccolo@unitn.it
M. Babaei
Department of Civil and Environmental Engineering
Department of Mechanical Engineering
Carnegie Mellon University
Pittsburgh, PA 15213
mbabaei@andrew.cmu.edu
Kaushik Dayal
Center for Nonlinear Analysis
Department of Civil and Environmental Engineering
Department of Materials Science and Engineering
Carnegie Mellon University
Pittsburgh, PA 15213
Kaushik.Dayal@cmu.edu
N. M. Pugno
Department of Civil, Environmental and Mechanical Engineering
University of Trento, Italy
Laboratory of Bio-inspired, Bionic, Nano, Meta Materials & Mechanics
Department of Civil, Environmental and Mechanical Engineering
University of Trento, Italy
Griffith Theory Centenary Lab, School of Engineering and Materials Science
Queen Mary University of London
London, UK
nicola.pugno@unitn.it
M. Zingales
Dipartimento di Ingegneria
Università di Palermo
Palermo, Italy
massimiliano.zingales@unipa.it
Luca Deseri
Department of Civil, Environmental and Mechanical Engineering
University of Trento, Italy
Department of Civil and Environmental Engineering, Department of Mechanical Engineering
Carnegie Mellon University, USA
Department of Mechanical Engineering and Material Sciences, SSoE
University of Pittsburgh, USA
Department of Nanomedicine
The Houston Methodist Research Institute, USA
Lud7@pitt.edu
M. Fraldi
Department of Structures for Engineering and Architecture
University of Naples
Italy
fraldi@unina.it
Abstract: Clustering of ligand-binding receptors of different types on thickened isles of the cell membrane, namely lipid rafts, is an experimentally observed phenomenon. Although its influence on cell's response is deeply investigated, the role of the coupling between mechanical processes and multiphysics involving the active receptors and the surrounding lipid membrane during ligand-binding has not yet been understood. Specifically, the focus of this work is on
G-protein-coupled receptors (GPCRs), the widest group of transmembrane proteins in animals, which regulate specific cell processes through chemical signalling pathways involving a synergistic balance between the
cyclic Adenosine Monophosphate (cAMP) produced by active GPCRs in the intracellular environment and its efflux, mediated by the
Multidrug Resistance Proteins (MRPs) transporters. This paper develops a multiphysics approach based on the interplay among energetics, multiscale geometrical changes and mass balance of species, i.e. active GPCRs and MRPs, including diffusion and kinetics of binding and unbinding. Because the obtained energy depends upon both the kinematics and the changes of species densities, balance of mass and of linear momentum are coupled and govern the space-time evolution of the cell membrane. The mechanobiology involving remodelling and change of lipid ordering of the cell membrane allows to predict dynamics of transporters and active receptors - in full agreement with experimentally observed cAMP levels - and how the latter trigger rafts formation and cluster on such sites. Within the current scientific debate on Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) and on the basis of the ascertained fact that lipid rafts often serve as an entry port for viruses, it is felt that approaches accounting for strong coupling among mechanobiological aspects could even turn helpful in better understanding membrane-mediated phenomena such as COVID-19 virus-cell interaction.
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