The main bulk of this Thesis is focused on the response of cell membranes due to chemical and mechanical stimuli. Henceforth, it is mainly devoted to deduce how the key aspect of the cell response activated by chemical signaling can be predicted by a simplified energetics, making use of both theoretical models and numerical simulations. The a ention is focused on cell membranes embedding G protein-coupled receptors (GPRCs). By analyzing the behavior of cell mem- branes, one can isolate three main contributions in order to model their respon- se: (1) diffusion of receptors and transporters embedded in the lipid membrane; (2) conformational changes of the receptors; (3) membrane elasticity. Moreover, the interplay between TM confomational changes and lateral pressure of the lipid membrane against such TMs is introduced. The chemical potential of the receptor-ligand compound, deduced as the variational derivative of such energy, is compared with the one calculated by accounting for the work done by the lateral pressure. The result yields a relationship between the conformational field, the mechanical field (interpreted as either the thickness change or the areal change) and the distribution of the compounds receptor-ligand. The analysis of such resulting constitutive equation among those three quantities shows that, essentially, the reason why ligand-GPRCs compounds prefer to live on lipid ra is a necessity involving the interplay between the work performed by the lateral pressure and the need of TMs to change their conformation during ligand binding. Henceforth, mechanobiology gives a justification to the experimental findings of Kobilka and Lei ovitz, Chemistry Nobel Prizes 2012.
| Identifer | oai:union.ndltd.org:unitn.it/oai:iris.unitn.it:11572/368815 |
| Date | January 2015 |
| Creators | Pollaci, Pietro |
| Contributors | Pollaci, Pietro, Deseri, Luca, Zingales, Massimiliano |
| Publisher | Università degli studi di Trento, place:TRENTO |
| Source Sets | Università di Trento |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | firstpage:1, lastpage:301, numberofpages:301 |
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