title: A thermo-physical analysis of the proton pump vacuolar-ATPase: the constructal approach.
abstract: Pumping protons across a membrane was a critical step at the origin of life on earth, and it is still performed in all living organisms, including in human cells. Proton pumping is paramount to keep normal cells alive, e.g. for lysosomal digestion and for preparing peptides for immune recognition, but it goes awry in cancer cells. They acidify their microenvironment hence membrane voltage is lowered, which in turn induces cell proliferation, a hallmark of cancer. Proton pumping is achieved by means of rotary motors, namely vacuolar ATPases (V-ATPase), which are present at many of the multiple cellular interfaces. Therefore, we undertook an examination of the thermodynamic properties of V-ATPases. The principal result is that the V-ATPase-mediated control of the cell membrane potential and the related and consequent environmental pH can potentially represent a valuable support strategy for anticancer therapies. A constructal theory approach is used as a new viewpoint to study how V-ATPase can be modulated for therapeutic purposes. In particular, V-ATPase can be regulated by using external fields, such as electromagnetic fields, and a theoretical approach has been introduced to quantify the appropriate field strength and frequency for this new adjuvant therapeutic strategy.
authors.affiliation: Dipartimento Energia, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Lucia
authors.affiliation: Department of Medical Sciences, University of Torino, Corso A.M. Dogliotti 14, 10126 Torino, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ponzetto
authors.affiliation: Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Deisboeck
mesh_terms: D000465:Algorithms; D008954:Models, Biological; D013816:Thermodynamics; D025262:Vacuolar Proton-Translocating ATPases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D025262:Vacuolar Proton-Translocating ATPases